Dysregulated immune responses including elevations in the inflammatory cytokines tumor necrosis factor (TNF),^1-4 IL- 1 β ,³ and IL-12/23^5-7 have been identified in hidradenitis suppurativa (HS). Targeted biologic agents may offer an opportunity to intervene in specific aberrant inflammatory pathways to effectively treat HS while minimizing a dverse effects (AEs). There is growing evidence, however, that treatment of HS with a single biologic agent is not effective in all patients.^6,8-17 The TNF antagonist adalimumab has been shown to achieve clinical response in approximately 50% of patients (N = 633). ¹⁸In smaller and uncontrolled studies, clinical response was achieved in 70% (7/10) of patients treated with the IL-1 antagonist anakinra¹⁶ and 47 % (8/17) of patients treated with the IL-12/23 antagonist ustekinumab¹⁹ ; however, larger rigorous studies are needed. There is an urgent need for more effective therapeutic strategies for this condition.²⁰

The administration of concurrent biologics may offer the potential for improved disease control through synergistic targeting of multiple inflammatory pathways, particularly for severe and recalcitrant HS. This approach may be effective given insights from mechanistic studies suggesting the involvement of multiple inflammatory pathways in the disease pathogenesis.^3,21 Concurrent anticytokine biologics have been used safely and effectively in other inflammatory diseases; for example, combination therapy with TNF and IL-12/23 antagonists have resulted in near-complete to complete resolution of severe psoriatic skin and joint disease without AEs.^22-24

An increased risk for infection without increased efficacy associated with the use of concurrent anticytokine biologics for treatment of rheumatoid arthritis (RA) has raised concerns about the safety of this therapeutic approach. In a study of concurrent etanercept and anakinra therapy for RA (N=244), the combined therapy was not more efficacious than etanercept alone (American College of Rheumatology 50% response at week 24: etanercept 25 mg twice weekly, 41%; etanercept 25 mg twice weekly plus anakinra 100 mg once daily, 31%; etanercept 25 mg once weekly plus anakinra 100 mg once daily, 39% [P=.914]).²⁵ Combination therapy also was associated with a higher overall incidence of serious AEs, serious infections requiring antibiotics or hospitalizations, and serious infections leading to study withdrawal. Reported infections included pneumonia, cellulitis, herpes zoster, pneumonitis, and pyelonephritis, but no opportunistic infections or tuberculosis were reported. A single case of lymphoma was reported in the full-dose etanercept plus anakinra group; however, the association with therapy is unclear, as RA itself is associated with an increased risk of malignancy.²⁵

Although these results are notable, caution must be exercised in extrapolating safety and efficacy data for treatment with concurrent biologics from the RA literature for management of HS for several reasons. First, RA is an autoimmune disease that is associated with an increased risk for genitourinary and bronchopulmonary infections and septic arthritis, even in the absence of treatment with steroids and immunomodulatory drugs.^26,27 Increased risk for development of lymphoma, lung cancer, and nonmelanoma skin cancer also has been associated with RA.^28,29 The exact etiology of this increased risk is unknown, but it is thought to relate to immunologic disturbances and chronic systemic inflammation associated with RA.²⁹ Furthermore, RA disease characteristics and comorbidities that may contribute to an increased risk for infection and malignancy include advanced age as well as a history of leukopenia, chronic lung disease, diabetes mellitus, alcoholism, and/or smoking.³⁰ Infection and malignancy risk in RA also may be compounded by immunomodulatory therapies.^31,32

Conversely, although microbes are believed to play an important role in HS initiation and progression, HS is neither considered an infectious disease nor associated with an increased risk for infection.³³ Increased malignancy risk generally is not reported with HS, and systematic therapeutic trials of biologic therapies for HS have been notable for an absence of infectious or malignant AEs compared to placebo.^{12,14,16,18,19} From a mechanistic standpoint, data suggest that HS may be fundamentally distinct from RA and other autoimmune diseases; therefore, it may not be appropriate to extrapolate safety data from the latter to guide therapeutic strategies for the former.

The concept that different inflammatory diseases harbor distinct risks for comorbidities and AEs associated with medications is further supported by data from patients with PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne), a monogenic autoinflammatory disease characterized by inflammasome activation and subsequent increased signaling via IL-1.³⁴Patients with PAPA syndrome often require a combination therapeutic regimen including simultaneous antibiotics, systemic retinoids and steroids, disease-modifying antirheumatic drugs, and more than 1 concurrent anticytokine biologic to manage their condition. Despite management with multiple immunosuppressants and immunomodulators, patients with PAPA syndrome rarely develop localized or systemic infections, supporting our hypothesis that different systemic immune-mediated disorders may render a distinct susceptibility to infectious complications. Clinically, patients with PAPA syndrome can have cutaneous disease manifestations consistent with HS, suggesting the possibility of shared underlying inflammatory mechanisms due at least partially to inflammasome activation. This clinical observation may help explain why concurrent anticytokine biologic therapies in conjunction with combinations of steroids and other immunomodulators may be safe and effective in HS patients.

We have safely and effectively treated 2 patients with severe HS with extended courses of concurrent TNF and IL-1 antagonists. Both patients had previously failed treatment with multiple therapeutic interventions, including topical and systemic antibiotics, disease-modifying antirheumatic drugs, hormonal therapy, biologic monotherapy with several targeted agents, and wide local excision. In the setting of concurrent certolizumab plus anakinra in the first patient and adalimumab plus anakinra in the second, both patients reported reduced drainage, pain, and number of disease flares. Both patients also were maintained on extended treatment courses (11 months and 2 years, respectively) without evidence of infection or malignancy.

Concurrent biologics may be safe and effective in managing recalcitrant HS; however, large prospective studies are needed to confirm these anecdotal findings. As our understanding of HS pathogenesis expands, novel and more effective therapeutic options will be developed. Until then, concurrent biologics may be a potential option for patients with severe recalcitrant HS.

Dysregulated immune responses including elevations in the inflammatory cytokines tumor necrosis factor (TNF),^1-4 IL- 1 β ,³ and IL-12/23^5-7 have been identified in hidradenitis suppurativa (HS). Targeted biologic agents may offer an opportunity to intervene in specific aberrant inflammatory pathways to effectively treat HS while minimizing a dverse effects (AEs). There is growing evidence, however, that treatment of HS with a single biologic agent is not effective in all patients.^6,8-17 The TNF antagonist adalimumab has been shown to achieve clinical response in approximately 50% of patients (N = 633). ¹⁸In smaller and uncontrolled studies, clinical response was achieved in 70% (7/10) of patients treated with the IL-1 antagonist anakinra¹⁶ and 47 % (8/17) of patients treated with the IL-12/23 antagonist ustekinumab¹⁹ ; however, larger rigorous studies are needed. There is an urgent need for more effective therapeutic strategies for this condition.²⁰

The administration of concurrent biologics may offer the potential for improved disease control through synergistic targeting of multiple inflammatory pathways, particularly for severe and recalcitrant HS. This approach may be effective given insights from mechanistic studies suggesting the involvement of multiple inflammatory pathways in the disease pathogenesis.^3,21 Concurrent anticytokine biologics have been used safely and effectively in other inflammatory diseases; for example, combination therapy with TNF and IL-12/23 antagonists have resulted in near-complete to complete resolution of severe psoriatic skin and joint disease without AEs.^22-24

An increased risk for infection without increased efficacy associated with the use of concurrent anticytokine biologics for treatment of rheumatoid arthritis (RA) has raised concerns about the safety of this therapeutic approach. In a study of concurrent etanercept and anakinra therapy for RA (N=244), the combined therapy was not more efficacious than etanercept alone (American College of Rheumatology 50% response at week 24: etanercept 25 mg twice weekly, 41%; etanercept 25 mg twice weekly plus anakinra 100 mg once daily, 31%; etanercept 25 mg once weekly plus anakinra 100 mg once daily, 39% [P=.914]).²⁵ Combination therapy also was associated with a higher overall incidence of serious AEs, serious infections requiring antibiotics or hospitalizations, and serious infections leading to study withdrawal. Reported infections included pneumonia, cellulitis, herpes zoster, pneumonitis, and pyelonephritis, but no opportunistic infections or tuberculosis were reported. A single case of lymphoma was reported in the full-dose etanercept plus anakinra group; however, the association with therapy is unclear, as RA itself is associated with an increased risk of malignancy.²⁵

Although these results are notable, caution must be exercised in extrapolating safety and efficacy data for treatment with concurrent biologics from the RA literature for management of HS for several reasons. First, RA is an autoimmune disease that is associated with an increased risk for genitourinary and bronchopulmonary infections and septic arthritis, even in the absence of treatment with steroids and immunomodulatory drugs.^26,27 Increased risk for development of lymphoma, lung cancer, and nonmelanoma skin cancer also has been associated with RA.^28,29 The exact etiology of this increased risk is unknown, but it is thought to relate to immunologic disturbances and chronic systemic inflammation associated with RA.²⁹ Furthermore, RA disease characteristics and comorbidities that may contribute to an increased risk for infection and malignancy include advanced age as well as a history of leukopenia, chronic lung disease, diabetes mellitus, alcoholism, and/or smoking.³⁰ Infection and malignancy risk in RA also may be compounded by immunomodulatory therapies.^31,32

Conversely, although microbes are believed to play an important role in HS initiation and progression, HS is neither considered an infectious disease nor associated with an increased risk for infection.³³ Increased malignancy risk generally is not reported with HS, and systematic therapeutic trials of biologic therapies for HS have been notable for an absence of infectious or malignant AEs compared to placebo.^{12,14,16,18,19} From a mechanistic standpoint, data suggest that HS may be fundamentally distinct from RA and other autoimmune diseases; therefore, it may not be appropriate to extrapolate safety data from the latter to guide therapeutic strategies for the former.

The concept that different inflammatory diseases harbor distinct risks for comorbidities and AEs associated with medications is further supported by data from patients with PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne), a monogenic autoinflammatory disease characterized by inflammasome activation and subsequent increased signaling via IL-1.³⁴Patients with PAPA syndrome often require a combination therapeutic regimen including simultaneous antibiotics, systemic retinoids and steroids, disease-modifying antirheumatic drugs, and more than 1 concurrent anticytokine biologic to manage their condition. Despite management with multiple immunosuppressants and immunomodulators, patients with PAPA syndrome rarely develop localized or systemic infections, supporting our hypothesis that different systemic immune-mediated disorders may render a distinct susceptibility to infectious complications. Clinically, patients with PAPA syndrome can have cutaneous disease manifestations consistent with HS, suggesting the possibility of shared underlying inflammatory mechanisms due at least partially to inflammasome activation. This clinical observation may help explain why concurrent anticytokine biologic therapies in conjunction with combinations of steroids and other immunomodulators may be safe and effective in HS patients.

We have safely and effectively treated 2 patients with severe HS with extended courses of concurrent TNF and IL-1 antagonists. Both patients had previously failed treatment with multiple therapeutic interventions, including topical and systemic antibiotics, disease-modifying antirheumatic drugs, hormonal therapy, biologic monotherapy with several targeted agents, and wide local excision. In the setting of concurrent certolizumab plus anakinra in the first patient and adalimumab plus anakinra in the second, both patients reported reduced drainage, pain, and number of disease flares. Both patients also were maintained on extended treatment courses (11 months and 2 years, respectively) without evidence of infection or malignancy.

Concurrent biologics may be safe and effective in managing recalcitrant HS; however, large prospective studies are needed to confirm these anecdotal findings. As our understanding of HS pathogenesis expands, novel and more effective therapeutic options will be developed. Until then, concurrent biologics may be a potential option for patients with severe recalcitrant HS.

Dysregulated immune responses including elevations in the inflammatory cytokines tumor necrosis factor (TNF),^1-4 IL- 1 β ,³ and IL-12/23^5-7 have been identified in hidradenitis suppurativa (HS). Targeted biologic agents may offer an opportunity to intervene in specific aberrant inflammatory pathways to effectively treat HS while minimizing a dverse effects (AEs). There is growing evidence, however, that treatment of HS with a single biologic agent is not effective in all patients.^6,8-17 The TNF antagonist adalimumab has been shown to achieve clinical response in approximately 50% of patients (N = 633). ¹⁸In smaller and uncontrolled studies, clinical response was achieved in 70% (7/10) of patients treated with the IL-1 antagonist anakinra¹⁶ and 47 % (8/17) of patients treated with the IL-12/23 antagonist ustekinumab¹⁹ ; however, larger rigorous studies are needed. There is an urgent need for more effective therapeutic strategies for this condition.²⁰

The administration of concurrent biologics may offer the potential for improved disease control through synergistic targeting of multiple inflammatory pathways, particularly for severe and recalcitrant HS. This approach may be effective given insights from mechanistic studies suggesting the involvement of multiple inflammatory pathways in the disease pathogenesis.^3,21 Concurrent anticytokine biologics have been used safely and effectively in other inflammatory diseases; for example, combination therapy with TNF and IL-12/23 antagonists have resulted in near-complete to complete resolution of severe psoriatic skin and joint disease without AEs.^22-24

An increased risk for infection without increased efficacy associated with the use of concurrent anticytokine biologics for treatment of rheumatoid arthritis (RA) has raised concerns about the safety of this therapeutic approach. In a study of concurrent etanercept and anakinra therapy for RA (N=244), the combined therapy was not more efficacious than etanercept alone (American College of Rheumatology 50% response at week 24: etanercept 25 mg twice weekly, 41%; etanercept 25 mg twice weekly plus anakinra 100 mg once daily, 31%; etanercept 25 mg once weekly plus anakinra 100 mg once daily, 39% [P=.914]).²⁵ Combination therapy also was associated with a higher overall incidence of serious AEs, serious infections requiring antibiotics or hospitalizations, and serious infections leading to study withdrawal. Reported infections included pneumonia, cellulitis, herpes zoster, pneumonitis, and pyelonephritis, but no opportunistic infections or tuberculosis were reported. A single case of lymphoma was reported in the full-dose etanercept plus anakinra group; however, the association with therapy is unclear, as RA itself is associated with an increased risk of malignancy.²⁵

Although these results are notable, caution must be exercised in extrapolating safety and efficacy data for treatment with concurrent biologics from the RA literature for management of HS for several reasons. First, RA is an autoimmune disease that is associated with an increased risk for genitourinary and bronchopulmonary infections and septic arthritis, even in the absence of treatment with steroids and immunomodulatory drugs.^26,27 Increased risk for development of lymphoma, lung cancer, and nonmelanoma skin cancer also has been associated with RA.^28,29 The exact etiology of this increased risk is unknown, but it is thought to relate to immunologic disturbances and chronic systemic inflammation associated with RA.²⁹ Furthermore, RA disease characteristics and comorbidities that may contribute to an increased risk for infection and malignancy include advanced age as well as a history of leukopenia, chronic lung disease, diabetes mellitus, alcoholism, and/or smoking.³⁰ Infection and malignancy risk in RA also may be compounded by immunomodulatory therapies.^31,32

Conversely, although microbes are believed to play an important role in HS initiation and progression, HS is neither considered an infectious disease nor associated with an increased risk for infection.³³ Increased malignancy risk generally is not reported with HS, and systematic therapeutic trials of biologic therapies for HS have been notable for an absence of infectious or malignant AEs compared to placebo.^{12,14,16,18,19} From a mechanistic standpoint, data suggest that HS may be fundamentally distinct from RA and other autoimmune diseases; therefore, it may not be appropriate to extrapolate safety data from the latter to guide therapeutic strategies for the former.

The concept that different inflammatory diseases harbor distinct risks for comorbidities and AEs associated with medications is further supported by data from patients with PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne), a monogenic autoinflammatory disease characterized by inflammasome activation and subsequent increased signaling via IL-1.³⁴Patients with PAPA syndrome often require a combination therapeutic regimen including simultaneous antibiotics, systemic retinoids and steroids, disease-modifying antirheumatic drugs, and more than 1 concurrent anticytokine biologic to manage their condition. Despite management with multiple immunosuppressants and immunomodulators, patients with PAPA syndrome rarely develop localized or systemic infections, supporting our hypothesis that different systemic immune-mediated disorders may render a distinct susceptibility to infectious complications. Clinically, patients with PAPA syndrome can have cutaneous disease manifestations consistent with HS, suggesting the possibility of shared underlying inflammatory mechanisms due at least partially to inflammasome activation. This clinical observation may help explain why concurrent anticytokine biologic therapies in conjunction with combinations of steroids and other immunomodulators may be safe and effective in HS patients.

We have safely and effectively treated 2 patients with severe HS with extended courses of concurrent TNF and IL-1 antagonists. Both patients had previously failed treatment with multiple therapeutic interventions, including topical and systemic antibiotics, disease-modifying antirheumatic drugs, hormonal therapy, biologic monotherapy with several targeted agents, and wide local excision. In the setting of concurrent certolizumab plus anakinra in the first patient and adalimumab plus anakinra in the second, both patients reported reduced drainage, pain, and number of disease flares. Both patients also were maintained on extended treatment courses (11 months and 2 years, respectively) without evidence of infection or malignancy.

Concurrent biologics may be safe and effective in managing recalcitrant HS; however, large prospective studies are needed to confirm these anecdotal findings. As our understanding of HS pathogenesis expands, novel and more effective therapeutic options will be developed. Until then, concurrent biologics may be a potential option for patients with severe recalcitrant HS.

Are more inhaled steroids better at blocking asthma exacerbations? A common skin disorder finds its way into more emergency departments, there are new guidelines for handling teen depression in primary care, and learn the five orthopedic tests to avoid in children.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Are more inhaled steroids better at blocking asthma exacerbations? A common skin disorder finds its way into more emergency departments, there are new guidelines for handling teen depression in primary care, and learn the five orthopedic tests to avoid in children.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Are more inhaled steroids better at blocking asthma exacerbations? A common skin disorder finds its way into more emergency departments, there are new guidelines for handling teen depression in primary care, and learn the five orthopedic tests to avoid in children.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Colorectal cancer (CRC) is an important concern for the VA, and colonoscopy is one primary screening, surveillance, and diagnostic modality used. The observed reductions in CRC incidence and mortality over the past decade largely have been attributed to the widespread use of CRC screening options.^1,2 Colonoscopy quality is critical to CRC prevention in veterans. However, endoscopy skills to detect and remove colorectal polyps using colonoscopy vary in practice.^3-5

Quality benchmarks, linked to patient outcomes, have been established by specialty societies and proposed by the Centers for Medicare and Medicaid Services as reportable quality metrics.⁶ Colonoscopy quality metrics have been shown to be associated with patient outcomes, such as the risk of developing CRC after colonoscopy. The adenoma detection rate (ADR), defined as the proportion of average-risk screening colonoscopies in which 1 or more adenomas are detected, has the strongest association to interval or “missed” CRC after screening colonoscopy and has been linked to a risk for fatal CRC despite colonoscopy.³

In a landmark study of 314,872 examinations performed by 136 gastroenterologists, the ADR ranged from 7.4% to 52.5%.³ Among patients with ADRs in the highest quintile compared with patients in the lowest, the adjusted hazard ratios (HRs) for any interval cancer was 0.52 (95% confidence interval [CI], 0.39-0.69) and for fatal interval cancers was 0.38 (95% CI, 0.22-0.65).³ Another pooled analysis from 8 surveillance studies that followed more than 800 participants with adenoma(s) after a baseline colonoscopy showed 52% of incident cancers as probable missed lesions, 19% as possibly related to incomplete resection of an earlier, noninvasive lesion, and only 24% as probable new lesions.⁷ These interval cancers highlight the current imperfections of colonoscopy and the focus on measurement and reporting of quality indicators for colonoscopy.^8-12

According to VHA Directive 1015, in December 2014, colonoscopy quality should be monitored as part of an ongoing quality assurance program.¹³ A recent report from the VA Office of the Inspector General (OIG) highlighted colonoscopy-quality deficiencies.¹⁴ The OIG report strongly recommended that the “Acting Under Secretary for Health require standardized documentation of quality indicators based on professional society guidelines and published literature.”¹⁴However, no currently standardized and readily available VHA resource measures, reports, and ensures colonoscopy quality.

The authors hypothesized that colonoscopy quality assurance programs vary widely across VHA sites. The objective of this survey was to assess the measurement and reporting practices for colonoscopy quality and identify both strengths and areas for improvement to facilitate implementation of quality assurance programs across the VA health care system.

Methods

The authors performed an online survey of VA sites to assess current colonoscopy quality assurance practices. The institutional review boards (IRBs) at the University of Utah and VA Salt Lake City Health Care System and University of California, San Francisco and San Francisco VA Health Care System classified the study as a quality improvement project that did not qualify for human subjects’ research requiring IRB review.

The authors iteratively developed and refined the questionnaire with a survey methodologist and 2 clinical domain experts. The National Program Director for Gastroenterology, and the National Gastroenterology Field Advisory Committee reviewed the survey content and pretested the survey instrument prior to final data collection. The National Program Office for Gastroenterology provided an e-mail list of all known VA gastroenterology section chiefs. The authors administered the final survey via e-mail, using the Research Electronic Data Capture (REDCap; Vanderbilt University Medical Center) platform beginning January 9, 2017.¹⁵

A follow-up reminder e-mail was sent to nonresponders after 2 weeks. After this second invitation, sites were contacted by telephone to verify that the correct contact information had been captured. Subsequently, 50 contacts were updated if e-mails bounced back or the correct contact was obtained. Points of contact received a total of 3 reminder e-mails until the final closeout of the survey on March 28, 2017; 65 of 89 (73%) of the original contacts completed the survey vs 31 of 50 (62%) of the updated contacts.

Analysis

Descriptive statistics of the responses were calculated to determine the overall proportion of VA sites measuring colonoscopy quality metrics and identification of areas in need of quality improvement. The response rate for the survey was defined as the total number of responses obtained as a proportion of the total number of points of contact. This corresponds to the American Association of Public Opinion Research’s RR1, or minimum response rate, formula.¹⁶ All categoric responses are presented as proportions. Statistical analyses were performed using STATA SE12.0 (College Station, TX).

Results

Of the 139 points of contact invited, 96 completed the survey (response rate of 69.0%), representing 93 VA facilities (of 141 possible facilities) in 44 different states. Three sites had 2 responses. Sites used various and often a combination of methods to measure quality (Table 1). 

A majority of sites’ (63.5%) quality reports represented individual provider data, whereas fewer provided quality reports for physician groups (22.9%) or for the entire facility (40.6%). Provider quality information was de-identified in 43.8% of reporting sites’ quality reports and identifiable in 37.5% of reporting sites’ quality reports. A majority of sites (74.0%) reported that the local gastroenterology section chief or quality manager has access to the quality reports. Fewer sites reported providing data to individual endoscopists (44.8% for personal and peer data and 32.3% for personal data only). One site (1%) responded that quality reports were available for public access. Survey respondents also were asked to provide the estimated time (hours required per month) to collect the data for quality metrics. Of 75 respondents providing data for this question, 28 (29.2%) and 17 (17.7%), estimated between 1 to 5 and 6 to 10 hours per month, respectively. Ten sites estimated spending between 11 to 20 hours, and 7 sites estimated spending more than 20 hours per month collecting quality metrics. A total of 13 respondents (13.5%) stated uncertainty about the time burden.

As shown in the Figure,  numerous quality metrics were collected across sites with more than 80% of sites collecting information on bowel preparation quality (88.5%), cecal intubation rate (87.5%), and complications (83.3%). A majority of sites also reported collecting data on appropriateness of surveillance intervals (62.5%), colonoscopy withdrawal times (62.5%), and ADRs (61.5%). Seven sites (7.3%) did not collect quality metrics.

Information also was collected on colonoscopy procedure documentation to inform future efforts at standardization. A small majority (53.1%) of sites reported using endoscopic software to generate colonoscopy procedure documentation. Within these sites, 6 different types of endoscopic note writing software were used to generate procedure notes (Table 2). 

Most sites (85.4%) were aware of VHA Directive 1015 recommendations for colonoscopy quality assurance programs. A significant majority (89.5%) of respondents also indicated interest in a centralized automatic reporting system to measure and report colonoscopy quality in some form, either with aggregate data, provider data, or both (Table 3).

Discussion

This survey on colonoscopy quality assurance programs is the first assessment of the VHA’s efforts to measure and report colonoscopy quality indicators. The findings indicated that the majority of VA sites are measuring and reporting at least some measures of colonoscopy quality. However, the programs are significantly variable in terms of methods used to collect quality metrics, specific quality measures obtained, and how quality is reported.

The authors’ work is novel in that this is the first report of the status of colonoscopy quality assurance programs in a large U.S. health care system. The VA health care system is the largest integrated health system in the U.S., serving more than 9 million veterans annually. This survey’s high response rate further strengthens the findings. Specifically, the survey found that VA sites are making a strong concerted effort to measure and report colonoscopy quality. However, there is significant variability in documentation, measurement, and reporting practices. Moreover, the majority of VA sites do not have formal performance improvement plans in place for endoscopists who do not meet thresholds for colonoscopy quality.

Screening colonoscopy for CRC offers known mortality benefits to patients.^1,17-19 Significant prior work has described and validated the importance of colonoscopy quality metrics, including bowel preparation quality, cecal intubation rate, and ADR and their association with interval colorectal cancer and death.^20-23 Gastroenterology professional societies, including the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, have recommended and endorsed measurement and reporting of colonoscopy metrics.²⁴ There is general agreement among endoscopists that colonoscopy quality is an important aspect of performing the procedure.

The lack of formal performance improvement programs is a key finding of this survey. Recent studies have shown that improvements in quality metrics, such as the ADR, by individual endoscopists result in reductions in interval colorectal cancer and death.²⁵ Kahi and colleagues previously showed that providing a quarterly report card improves colonoscopy quality.²⁶ Keswani and colleagues studied a combination of a report card and implementation of standards of practice with resultant improvement in colonoscopy quality.²⁷ Most recently, in a large prospective cohort study of individuals who underwent a screening colonoscopy, 294 of the screening endoscopists received annual feedback and quality benchmark indicators to improve colonoscopy performance.²⁵ The majority of the endoscopists (74.5%) increased their annual ADR category over the study period. Moreover, patients examined by endoscopists who reached or maintained the highest ADR quintile (> 24.6%) had significantly lower risk of interval CRC and death. The lack of formal performance improvement programs across the VHA is concerning but reveals a significant opportunity to improve veteran health outcomes on a large scale.

This study’s findings also highlight the intense resources necessary to measure and report colonoscopy quality. The ability to measure and report quality metrics requires having adequate documentation and data to obtain quality metrics. Administrative databases from electronic health records offer some potential for routine monitoring of quality metrics.²⁸ However, most administrative databases, including the VA Corporate Data Warehouse (CDW), contain administrative billing codes (ICD and CPT) linked to limited patient data, including demographics and structured medical record data. The actual data required for quality reporting of important metrics (bowel preparation quality, cecal intubation rates, and ADRs) are usually found in clinical text notes or endoscopic note documentation and not available as structured data. Due to this issue, the majority of VA sites (79.2%) are using manual chart review to collect quality metric data, resulting in widely variable estimates on time burden. A minority of sites in this study (39.6%) reported using automated endoscopic software reporting capability that can help with the time burden. However, even in the VA, an integrated health system, a wide variety of software brands, documentation practices, and photo documentation was found.

Future endoscopy budget and purchase decisions for the individual VA sites should take into account how new technology and software can more easily facilitate accurate quality reporting. A specific policy recommendation would be for the VA to consider a uniform endoscopic note writer for procedure notes. Pathology data, which is necessary for the calculation of ADR, also should be available as structured data in the CDW to more easily measure colonoscopy quality. Continuous measurement and reporting of quality also requires ongoing information technology infrastructure and quality control of the measurement process.

Limitations

This survey was a cross-section of VA sites’ points of contact regarding colonoscopy quality assurance programs, so the results are descriptive in nature. However, the instrument was carefully developed, using both subject matter and survey method expertise. The questionnaire also was refined through pretesting prior to data collection. The initial contact list was found to have errors, and the list had to be updated after launching the survey. Updated information for most of the contacts was available.

Another limitation was the inability to survey nongastroenterologist-run endoscopy centers, because many centers use surgeons or other nongastroenterology providers. The authors speculate that quality monitoring may be less likely to be present at these facilities as they may not be aware of the gastroenterology professional society recommendations. The authors did not require or insist that all questions be answered, so some data were missing from sites. However, 93.7% of respondents completed the entire survey.

Conclusion

The authors have described the status of colonoscopy quality assurance programs across the VA health care system. Many sites are making robust efforts to measure and report quality especially of process measures. However, there are significant time and manual workforce efforts required, and this work is likely associated with the variability in programs. Importantly, ADR, which is the quality metric that has been most strongly associated with risk of colon cancer mortality, is not being measured by 38% of sites.

These results reinforce a critical need for a centralized, automated quality reporting infrastructure to standardize colonoscopy quality reporting, reduce workload, and ensure veterans receive high-quality colonoscopy.

Acknowledgments
The authors acknowledge the support and feedback of the National Gastroenterology Program Field Advisory Committee for survey development and testing. The authors coordinated the survey through the Salt Lake City Specialty Care Center of Innovation in partnership with the National Gastroenterology Program Office and the Quality Enhancement Research Initiative: Quality Enhancement Research Initiative, Measurement Science Program, QUE15-283. The work also was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award UL1TR001067 and Merit Review Award 1 I01 HX001574-01A1 from the United States Department of Veterans Affairs Health Services Research & Development Service of the VA Office of Research and Development.

Colorectal cancer (CRC) is an important concern for the VA, and colonoscopy is one primary screening, surveillance, and diagnostic modality used. The observed reductions in CRC incidence and mortality over the past decade largely have been attributed to the widespread use of CRC screening options.^1,2 Colonoscopy quality is critical to CRC prevention in veterans. However, endoscopy skills to detect and remove colorectal polyps using colonoscopy vary in practice.^3-5

Quality benchmarks, linked to patient outcomes, have been established by specialty societies and proposed by the Centers for Medicare and Medicaid Services as reportable quality metrics.⁶ Colonoscopy quality metrics have been shown to be associated with patient outcomes, such as the risk of developing CRC after colonoscopy. The adenoma detection rate (ADR), defined as the proportion of average-risk screening colonoscopies in which 1 or more adenomas are detected, has the strongest association to interval or “missed” CRC after screening colonoscopy and has been linked to a risk for fatal CRC despite colonoscopy.³

In a landmark study of 314,872 examinations performed by 136 gastroenterologists, the ADR ranged from 7.4% to 52.5%.³ Among patients with ADRs in the highest quintile compared with patients in the lowest, the adjusted hazard ratios (HRs) for any interval cancer was 0.52 (95% confidence interval [CI], 0.39-0.69) and for fatal interval cancers was 0.38 (95% CI, 0.22-0.65).³ Another pooled analysis from 8 surveillance studies that followed more than 800 participants with adenoma(s) after a baseline colonoscopy showed 52% of incident cancers as probable missed lesions, 19% as possibly related to incomplete resection of an earlier, noninvasive lesion, and only 24% as probable new lesions.⁷ These interval cancers highlight the current imperfections of colonoscopy and the focus on measurement and reporting of quality indicators for colonoscopy.^8-12

According to VHA Directive 1015, in December 2014, colonoscopy quality should be monitored as part of an ongoing quality assurance program.¹³ A recent report from the VA Office of the Inspector General (OIG) highlighted colonoscopy-quality deficiencies.¹⁴ The OIG report strongly recommended that the “Acting Under Secretary for Health require standardized documentation of quality indicators based on professional society guidelines and published literature.”¹⁴However, no currently standardized and readily available VHA resource measures, reports, and ensures colonoscopy quality.

The authors hypothesized that colonoscopy quality assurance programs vary widely across VHA sites. The objective of this survey was to assess the measurement and reporting practices for colonoscopy quality and identify both strengths and areas for improvement to facilitate implementation of quality assurance programs across the VA health care system.

Methods

The authors performed an online survey of VA sites to assess current colonoscopy quality assurance practices. The institutional review boards (IRBs) at the University of Utah and VA Salt Lake City Health Care System and University of California, San Francisco and San Francisco VA Health Care System classified the study as a quality improvement project that did not qualify for human subjects’ research requiring IRB review.

The authors iteratively developed and refined the questionnaire with a survey methodologist and 2 clinical domain experts. The National Program Director for Gastroenterology, and the National Gastroenterology Field Advisory Committee reviewed the survey content and pretested the survey instrument prior to final data collection. The National Program Office for Gastroenterology provided an e-mail list of all known VA gastroenterology section chiefs. The authors administered the final survey via e-mail, using the Research Electronic Data Capture (REDCap; Vanderbilt University Medical Center) platform beginning January 9, 2017.¹⁵

A follow-up reminder e-mail was sent to nonresponders after 2 weeks. After this second invitation, sites were contacted by telephone to verify that the correct contact information had been captured. Subsequently, 50 contacts were updated if e-mails bounced back or the correct contact was obtained. Points of contact received a total of 3 reminder e-mails until the final closeout of the survey on March 28, 2017; 65 of 89 (73%) of the original contacts completed the survey vs 31 of 50 (62%) of the updated contacts.

Analysis

Descriptive statistics of the responses were calculated to determine the overall proportion of VA sites measuring colonoscopy quality metrics and identification of areas in need of quality improvement. The response rate for the survey was defined as the total number of responses obtained as a proportion of the total number of points of contact. This corresponds to the American Association of Public Opinion Research’s RR1, or minimum response rate, formula.¹⁶ All categoric responses are presented as proportions. Statistical analyses were performed using STATA SE12.0 (College Station, TX).

Results

Of the 139 points of contact invited, 96 completed the survey (response rate of 69.0%), representing 93 VA facilities (of 141 possible facilities) in 44 different states. Three sites had 2 responses. Sites used various and often a combination of methods to measure quality (Table 1). 

A majority of sites’ (63.5%) quality reports represented individual provider data, whereas fewer provided quality reports for physician groups (22.9%) or for the entire facility (40.6%). Provider quality information was de-identified in 43.8% of reporting sites’ quality reports and identifiable in 37.5% of reporting sites’ quality reports. A majority of sites (74.0%) reported that the local gastroenterology section chief or quality manager has access to the quality reports. Fewer sites reported providing data to individual endoscopists (44.8% for personal and peer data and 32.3% for personal data only). One site (1%) responded that quality reports were available for public access. Survey respondents also were asked to provide the estimated time (hours required per month) to collect the data for quality metrics. Of 75 respondents providing data for this question, 28 (29.2%) and 17 (17.7%), estimated between 1 to 5 and 6 to 10 hours per month, respectively. Ten sites estimated spending between 11 to 20 hours, and 7 sites estimated spending more than 20 hours per month collecting quality metrics. A total of 13 respondents (13.5%) stated uncertainty about the time burden.

As shown in the Figure,  numerous quality metrics were collected across sites with more than 80% of sites collecting information on bowel preparation quality (88.5%), cecal intubation rate (87.5%), and complications (83.3%). A majority of sites also reported collecting data on appropriateness of surveillance intervals (62.5%), colonoscopy withdrawal times (62.5%), and ADRs (61.5%). Seven sites (7.3%) did not collect quality metrics.

Information also was collected on colonoscopy procedure documentation to inform future efforts at standardization. A small majority (53.1%) of sites reported using endoscopic software to generate colonoscopy procedure documentation. Within these sites, 6 different types of endoscopic note writing software were used to generate procedure notes (Table 2). 

Most sites (85.4%) were aware of VHA Directive 1015 recommendations for colonoscopy quality assurance programs. A significant majority (89.5%) of respondents also indicated interest in a centralized automatic reporting system to measure and report colonoscopy quality in some form, either with aggregate data, provider data, or both (Table 3).

Discussion

This survey on colonoscopy quality assurance programs is the first assessment of the VHA’s efforts to measure and report colonoscopy quality indicators. The findings indicated that the majority of VA sites are measuring and reporting at least some measures of colonoscopy quality. However, the programs are significantly variable in terms of methods used to collect quality metrics, specific quality measures obtained, and how quality is reported.

The authors’ work is novel in that this is the first report of the status of colonoscopy quality assurance programs in a large U.S. health care system. The VA health care system is the largest integrated health system in the U.S., serving more than 9 million veterans annually. This survey’s high response rate further strengthens the findings. Specifically, the survey found that VA sites are making a strong concerted effort to measure and report colonoscopy quality. However, there is significant variability in documentation, measurement, and reporting practices. Moreover, the majority of VA sites do not have formal performance improvement plans in place for endoscopists who do not meet thresholds for colonoscopy quality.

Screening colonoscopy for CRC offers known mortality benefits to patients.^1,17-19 Significant prior work has described and validated the importance of colonoscopy quality metrics, including bowel preparation quality, cecal intubation rate, and ADR and their association with interval colorectal cancer and death.^20-23 Gastroenterology professional societies, including the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, have recommended and endorsed measurement and reporting of colonoscopy metrics.²⁴ There is general agreement among endoscopists that colonoscopy quality is an important aspect of performing the procedure.

The lack of formal performance improvement programs is a key finding of this survey. Recent studies have shown that improvements in quality metrics, such as the ADR, by individual endoscopists result in reductions in interval colorectal cancer and death.²⁵ Kahi and colleagues previously showed that providing a quarterly report card improves colonoscopy quality.²⁶ Keswani and colleagues studied a combination of a report card and implementation of standards of practice with resultant improvement in colonoscopy quality.²⁷ Most recently, in a large prospective cohort study of individuals who underwent a screening colonoscopy, 294 of the screening endoscopists received annual feedback and quality benchmark indicators to improve colonoscopy performance.²⁵ The majority of the endoscopists (74.5%) increased their annual ADR category over the study period. Moreover, patients examined by endoscopists who reached or maintained the highest ADR quintile (> 24.6%) had significantly lower risk of interval CRC and death. The lack of formal performance improvement programs across the VHA is concerning but reveals a significant opportunity to improve veteran health outcomes on a large scale.

This study’s findings also highlight the intense resources necessary to measure and report colonoscopy quality. The ability to measure and report quality metrics requires having adequate documentation and data to obtain quality metrics. Administrative databases from electronic health records offer some potential for routine monitoring of quality metrics.²⁸ However, most administrative databases, including the VA Corporate Data Warehouse (CDW), contain administrative billing codes (ICD and CPT) linked to limited patient data, including demographics and structured medical record data. The actual data required for quality reporting of important metrics (bowel preparation quality, cecal intubation rates, and ADRs) are usually found in clinical text notes or endoscopic note documentation and not available as structured data. Due to this issue, the majority of VA sites (79.2%) are using manual chart review to collect quality metric data, resulting in widely variable estimates on time burden. A minority of sites in this study (39.6%) reported using automated endoscopic software reporting capability that can help with the time burden. However, even in the VA, an integrated health system, a wide variety of software brands, documentation practices, and photo documentation was found.

Future endoscopy budget and purchase decisions for the individual VA sites should take into account how new technology and software can more easily facilitate accurate quality reporting. A specific policy recommendation would be for the VA to consider a uniform endoscopic note writer for procedure notes. Pathology data, which is necessary for the calculation of ADR, also should be available as structured data in the CDW to more easily measure colonoscopy quality. Continuous measurement and reporting of quality also requires ongoing information technology infrastructure and quality control of the measurement process.

Limitations

This survey was a cross-section of VA sites’ points of contact regarding colonoscopy quality assurance programs, so the results are descriptive in nature. However, the instrument was carefully developed, using both subject matter and survey method expertise. The questionnaire also was refined through pretesting prior to data collection. The initial contact list was found to have errors, and the list had to be updated after launching the survey. Updated information for most of the contacts was available.

Another limitation was the inability to survey nongastroenterologist-run endoscopy centers, because many centers use surgeons or other nongastroenterology providers. The authors speculate that quality monitoring may be less likely to be present at these facilities as they may not be aware of the gastroenterology professional society recommendations. The authors did not require or insist that all questions be answered, so some data were missing from sites. However, 93.7% of respondents completed the entire survey.

Conclusion

The authors have described the status of colonoscopy quality assurance programs across the VA health care system. Many sites are making robust efforts to measure and report quality especially of process measures. However, there are significant time and manual workforce efforts required, and this work is likely associated with the variability in programs. Importantly, ADR, which is the quality metric that has been most strongly associated with risk of colon cancer mortality, is not being measured by 38% of sites.

These results reinforce a critical need for a centralized, automated quality reporting infrastructure to standardize colonoscopy quality reporting, reduce workload, and ensure veterans receive high-quality colonoscopy.

Acknowledgments
The authors acknowledge the support and feedback of the National Gastroenterology Program Field Advisory Committee for survey development and testing. The authors coordinated the survey through the Salt Lake City Specialty Care Center of Innovation in partnership with the National Gastroenterology Program Office and the Quality Enhancement Research Initiative: Quality Enhancement Research Initiative, Measurement Science Program, QUE15-283. The work also was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award UL1TR001067 and Merit Review Award 1 I01 HX001574-01A1 from the United States Department of Veterans Affairs Health Services Research & Development Service of the VA Office of Research and Development.

Colorectal cancer (CRC) is an important concern for the VA, and colonoscopy is one primary screening, surveillance, and diagnostic modality used. The observed reductions in CRC incidence and mortality over the past decade largely have been attributed to the widespread use of CRC screening options.^1,2 Colonoscopy quality is critical to CRC prevention in veterans. However, endoscopy skills to detect and remove colorectal polyps using colonoscopy vary in practice.^3-5

Quality benchmarks, linked to patient outcomes, have been established by specialty societies and proposed by the Centers for Medicare and Medicaid Services as reportable quality metrics.⁶ Colonoscopy quality metrics have been shown to be associated with patient outcomes, such as the risk of developing CRC after colonoscopy. The adenoma detection rate (ADR), defined as the proportion of average-risk screening colonoscopies in which 1 or more adenomas are detected, has the strongest association to interval or “missed” CRC after screening colonoscopy and has been linked to a risk for fatal CRC despite colonoscopy.³

In a landmark study of 314,872 examinations performed by 136 gastroenterologists, the ADR ranged from 7.4% to 52.5%.³ Among patients with ADRs in the highest quintile compared with patients in the lowest, the adjusted hazard ratios (HRs) for any interval cancer was 0.52 (95% confidence interval [CI], 0.39-0.69) and for fatal interval cancers was 0.38 (95% CI, 0.22-0.65).³ Another pooled analysis from 8 surveillance studies that followed more than 800 participants with adenoma(s) after a baseline colonoscopy showed 52% of incident cancers as probable missed lesions, 19% as possibly related to incomplete resection of an earlier, noninvasive lesion, and only 24% as probable new lesions.⁷ These interval cancers highlight the current imperfections of colonoscopy and the focus on measurement and reporting of quality indicators for colonoscopy.^8-12

According to VHA Directive 1015, in December 2014, colonoscopy quality should be monitored as part of an ongoing quality assurance program.¹³ A recent report from the VA Office of the Inspector General (OIG) highlighted colonoscopy-quality deficiencies.¹⁴ The OIG report strongly recommended that the “Acting Under Secretary for Health require standardized documentation of quality indicators based on professional society guidelines and published literature.”¹⁴However, no currently standardized and readily available VHA resource measures, reports, and ensures colonoscopy quality.

The authors hypothesized that colonoscopy quality assurance programs vary widely across VHA sites. The objective of this survey was to assess the measurement and reporting practices for colonoscopy quality and identify both strengths and areas for improvement to facilitate implementation of quality assurance programs across the VA health care system.

Methods

The authors performed an online survey of VA sites to assess current colonoscopy quality assurance practices. The institutional review boards (IRBs) at the University of Utah and VA Salt Lake City Health Care System and University of California, San Francisco and San Francisco VA Health Care System classified the study as a quality improvement project that did not qualify for human subjects’ research requiring IRB review.

The authors iteratively developed and refined the questionnaire with a survey methodologist and 2 clinical domain experts. The National Program Director for Gastroenterology, and the National Gastroenterology Field Advisory Committee reviewed the survey content and pretested the survey instrument prior to final data collection. The National Program Office for Gastroenterology provided an e-mail list of all known VA gastroenterology section chiefs. The authors administered the final survey via e-mail, using the Research Electronic Data Capture (REDCap; Vanderbilt University Medical Center) platform beginning January 9, 2017.¹⁵

A follow-up reminder e-mail was sent to nonresponders after 2 weeks. After this second invitation, sites were contacted by telephone to verify that the correct contact information had been captured. Subsequently, 50 contacts were updated if e-mails bounced back or the correct contact was obtained. Points of contact received a total of 3 reminder e-mails until the final closeout of the survey on March 28, 2017; 65 of 89 (73%) of the original contacts completed the survey vs 31 of 50 (62%) of the updated contacts.

Analysis

Descriptive statistics of the responses were calculated to determine the overall proportion of VA sites measuring colonoscopy quality metrics and identification of areas in need of quality improvement. The response rate for the survey was defined as the total number of responses obtained as a proportion of the total number of points of contact. This corresponds to the American Association of Public Opinion Research’s RR1, or minimum response rate, formula.¹⁶ All categoric responses are presented as proportions. Statistical analyses were performed using STATA SE12.0 (College Station, TX).

Results

Of the 139 points of contact invited, 96 completed the survey (response rate of 69.0%), representing 93 VA facilities (of 141 possible facilities) in 44 different states. Three sites had 2 responses. Sites used various and often a combination of methods to measure quality (Table 1). 

A majority of sites’ (63.5%) quality reports represented individual provider data, whereas fewer provided quality reports for physician groups (22.9%) or for the entire facility (40.6%). Provider quality information was de-identified in 43.8% of reporting sites’ quality reports and identifiable in 37.5% of reporting sites’ quality reports. A majority of sites (74.0%) reported that the local gastroenterology section chief or quality manager has access to the quality reports. Fewer sites reported providing data to individual endoscopists (44.8% for personal and peer data and 32.3% for personal data only). One site (1%) responded that quality reports were available for public access. Survey respondents also were asked to provide the estimated time (hours required per month) to collect the data for quality metrics. Of 75 respondents providing data for this question, 28 (29.2%) and 17 (17.7%), estimated between 1 to 5 and 6 to 10 hours per month, respectively. Ten sites estimated spending between 11 to 20 hours, and 7 sites estimated spending more than 20 hours per month collecting quality metrics. A total of 13 respondents (13.5%) stated uncertainty about the time burden.

As shown in the Figure,  numerous quality metrics were collected across sites with more than 80% of sites collecting information on bowel preparation quality (88.5%), cecal intubation rate (87.5%), and complications (83.3%). A majority of sites also reported collecting data on appropriateness of surveillance intervals (62.5%), colonoscopy withdrawal times (62.5%), and ADRs (61.5%). Seven sites (7.3%) did not collect quality metrics.

Information also was collected on colonoscopy procedure documentation to inform future efforts at standardization. A small majority (53.1%) of sites reported using endoscopic software to generate colonoscopy procedure documentation. Within these sites, 6 different types of endoscopic note writing software were used to generate procedure notes (Table 2). 

Most sites (85.4%) were aware of VHA Directive 1015 recommendations for colonoscopy quality assurance programs. A significant majority (89.5%) of respondents also indicated interest in a centralized automatic reporting system to measure and report colonoscopy quality in some form, either with aggregate data, provider data, or both (Table 3).

Discussion

This survey on colonoscopy quality assurance programs is the first assessment of the VHA’s efforts to measure and report colonoscopy quality indicators. The findings indicated that the majority of VA sites are measuring and reporting at least some measures of colonoscopy quality. However, the programs are significantly variable in terms of methods used to collect quality metrics, specific quality measures obtained, and how quality is reported.

The authors’ work is novel in that this is the first report of the status of colonoscopy quality assurance programs in a large U.S. health care system. The VA health care system is the largest integrated health system in the U.S., serving more than 9 million veterans annually. This survey’s high response rate further strengthens the findings. Specifically, the survey found that VA sites are making a strong concerted effort to measure and report colonoscopy quality. However, there is significant variability in documentation, measurement, and reporting practices. Moreover, the majority of VA sites do not have formal performance improvement plans in place for endoscopists who do not meet thresholds for colonoscopy quality.

Screening colonoscopy for CRC offers known mortality benefits to patients.^1,17-19 Significant prior work has described and validated the importance of colonoscopy quality metrics, including bowel preparation quality, cecal intubation rate, and ADR and their association with interval colorectal cancer and death.^20-23 Gastroenterology professional societies, including the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, have recommended and endorsed measurement and reporting of colonoscopy metrics.²⁴ There is general agreement among endoscopists that colonoscopy quality is an important aspect of performing the procedure.

The lack of formal performance improvement programs is a key finding of this survey. Recent studies have shown that improvements in quality metrics, such as the ADR, by individual endoscopists result in reductions in interval colorectal cancer and death.²⁵ Kahi and colleagues previously showed that providing a quarterly report card improves colonoscopy quality.²⁶ Keswani and colleagues studied a combination of a report card and implementation of standards of practice with resultant improvement in colonoscopy quality.²⁷ Most recently, in a large prospective cohort study of individuals who underwent a screening colonoscopy, 294 of the screening endoscopists received annual feedback and quality benchmark indicators to improve colonoscopy performance.²⁵ The majority of the endoscopists (74.5%) increased their annual ADR category over the study period. Moreover, patients examined by endoscopists who reached or maintained the highest ADR quintile (> 24.6%) had significantly lower risk of interval CRC and death. The lack of formal performance improvement programs across the VHA is concerning but reveals a significant opportunity to improve veteran health outcomes on a large scale.

This study’s findings also highlight the intense resources necessary to measure and report colonoscopy quality. The ability to measure and report quality metrics requires having adequate documentation and data to obtain quality metrics. Administrative databases from electronic health records offer some potential for routine monitoring of quality metrics.²⁸ However, most administrative databases, including the VA Corporate Data Warehouse (CDW), contain administrative billing codes (ICD and CPT) linked to limited patient data, including demographics and structured medical record data. The actual data required for quality reporting of important metrics (bowel preparation quality, cecal intubation rates, and ADRs) are usually found in clinical text notes or endoscopic note documentation and not available as structured data. Due to this issue, the majority of VA sites (79.2%) are using manual chart review to collect quality metric data, resulting in widely variable estimates on time burden. A minority of sites in this study (39.6%) reported using automated endoscopic software reporting capability that can help with the time burden. However, even in the VA, an integrated health system, a wide variety of software brands, documentation practices, and photo documentation was found.

Future endoscopy budget and purchase decisions for the individual VA sites should take into account how new technology and software can more easily facilitate accurate quality reporting. A specific policy recommendation would be for the VA to consider a uniform endoscopic note writer for procedure notes. Pathology data, which is necessary for the calculation of ADR, also should be available as structured data in the CDW to more easily measure colonoscopy quality. Continuous measurement and reporting of quality also requires ongoing information technology infrastructure and quality control of the measurement process.

Limitations

This survey was a cross-section of VA sites’ points of contact regarding colonoscopy quality assurance programs, so the results are descriptive in nature. However, the instrument was carefully developed, using both subject matter and survey method expertise. The questionnaire also was refined through pretesting prior to data collection. The initial contact list was found to have errors, and the list had to be updated after launching the survey. Updated information for most of the contacts was available.

Another limitation was the inability to survey nongastroenterologist-run endoscopy centers, because many centers use surgeons or other nongastroenterology providers. The authors speculate that quality monitoring may be less likely to be present at these facilities as they may not be aware of the gastroenterology professional society recommendations. The authors did not require or insist that all questions be answered, so some data were missing from sites. However, 93.7% of respondents completed the entire survey.

Conclusion

The authors have described the status of colonoscopy quality assurance programs across the VA health care system. Many sites are making robust efforts to measure and report quality especially of process measures. However, there are significant time and manual workforce efforts required, and this work is likely associated with the variability in programs. Importantly, ADR, which is the quality metric that has been most strongly associated with risk of colon cancer mortality, is not being measured by 38% of sites.

These results reinforce a critical need for a centralized, automated quality reporting infrastructure to standardize colonoscopy quality reporting, reduce workload, and ensure veterans receive high-quality colonoscopy.

Acknowledgments
The authors acknowledge the support and feedback of the National Gastroenterology Program Field Advisory Committee for survey development and testing. The authors coordinated the survey through the Salt Lake City Specialty Care Center of Innovation in partnership with the National Gastroenterology Program Office and the Quality Enhancement Research Initiative: Quality Enhancement Research Initiative, Measurement Science Program, QUE15-283. The work also was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award UL1TR001067 and Merit Review Award 1 I01 HX001574-01A1 from the United States Department of Veterans Affairs Health Services Research & Development Service of the VA Office of Research and Development.

Micrograph showing ALL

Researchers say they have developed a technique that can help them determine, at diagnosis, whether children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) will relapse after treatment.

The method involves examining individual leukemia cells using mass cytometry.

In looking at the cells’ stage of development and signaling behavior, the researchers were able to identify a subset of malignant cells that predispose a patient to relapse.

The team described this method, which they termed “developmentally dependent predictor of relapse (DDPR),” in Nature Medicine.

Prior research suggested relapse may be driven by treatment-resistant cells that are present from the beginning of disease development.

“We wondered, can we identify those cells at the time the patient first presents to the clinic, and can we treat patients with a specific therapy to target them?” said study author Kara Davis, DO, of Stanford University in California.

Dr Davis and her colleagues used mass cytometry to analyze diagnostic bone marrow samples from 60 patients with BCP-ALL.

To pinpoint the problematic cells among the millions of cells in each patient’s sample, the researchers had to figure out how to organize the data.

“Every patient has vastly different features to their cancer,” Dr Davis said, “and we had to ask, ‘Is there any common thread between them?’”

The solution, the researchers found, was to match BCP-ALL cells and healthy B cells according to their developmental states, comparing the leukemic cells to the healthy cells.

The comparison revealed 6 features of leukemic cell populations that were associated with relapse.

Broadly, the features suggested that pro-BII cells with activated mTOR signaling were associated with relapse, as were pre-BI cells with activated and unresponsive pre-B-cell receptor signaling.

“We do not understand the mechanisms by which malignant cells from the pro-BII and pre-BI stages of development resist treatment,” Dr Davis noted.

However, she and her colleagues were able to show the leukemic cell features identified by DDPR could predict relapse in the BCP-ALL patients.

Of the 60 patients analyzed, there were 54 with at least 3 years of follow-up. The researchers divided these patients into a training cohort (n=44) and a validation cohort (n=10).

The team used an integrated cumulative/dynamic area under the curve (iAUC) and a C-statistic to assess DDPR performance in both cohorts.

In the training cohort, DDPR had an iAUC value of 0.92 and a C-statistic of 0.87. In the validation cohort, DDPR had an iAUC value of 0.85 and a C-statistic of 0.87.

The researchers also said DDPR “performed well” in predicting relapse-free survival in a retrospective analysis of both cohorts (P = 2.8 × 10⁻⁷).

Now, the researchers plan to validate DDPR in a larger number of patients and evaluate whether the same general approach could predict relapse in other cancers.

Micrograph showing ALL

Researchers say they have developed a technique that can help them determine, at diagnosis, whether children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) will relapse after treatment.

The method involves examining individual leukemia cells using mass cytometry.

In looking at the cells’ stage of development and signaling behavior, the researchers were able to identify a subset of malignant cells that predispose a patient to relapse.

The team described this method, which they termed “developmentally dependent predictor of relapse (DDPR),” in Nature Medicine.

Prior research suggested relapse may be driven by treatment-resistant cells that are present from the beginning of disease development.

“We wondered, can we identify those cells at the time the patient first presents to the clinic, and can we treat patients with a specific therapy to target them?” said study author Kara Davis, DO, of Stanford University in California.

Dr Davis and her colleagues used mass cytometry to analyze diagnostic bone marrow samples from 60 patients with BCP-ALL.

To pinpoint the problematic cells among the millions of cells in each patient’s sample, the researchers had to figure out how to organize the data.

“Every patient has vastly different features to their cancer,” Dr Davis said, “and we had to ask, ‘Is there any common thread between them?’”

The solution, the researchers found, was to match BCP-ALL cells and healthy B cells according to their developmental states, comparing the leukemic cells to the healthy cells.

The comparison revealed 6 features of leukemic cell populations that were associated with relapse.

Broadly, the features suggested that pro-BII cells with activated mTOR signaling were associated with relapse, as were pre-BI cells with activated and unresponsive pre-B-cell receptor signaling.

“We do not understand the mechanisms by which malignant cells from the pro-BII and pre-BI stages of development resist treatment,” Dr Davis noted.

However, she and her colleagues were able to show the leukemic cell features identified by DDPR could predict relapse in the BCP-ALL patients.

Of the 60 patients analyzed, there were 54 with at least 3 years of follow-up. The researchers divided these patients into a training cohort (n=44) and a validation cohort (n=10).

The team used an integrated cumulative/dynamic area under the curve (iAUC) and a C-statistic to assess DDPR performance in both cohorts.

In the training cohort, DDPR had an iAUC value of 0.92 and a C-statistic of 0.87. In the validation cohort, DDPR had an iAUC value of 0.85 and a C-statistic of 0.87.

The researchers also said DDPR “performed well” in predicting relapse-free survival in a retrospective analysis of both cohorts (P = 2.8 × 10⁻⁷).

Now, the researchers plan to validate DDPR in a larger number of patients and evaluate whether the same general approach could predict relapse in other cancers.

Micrograph showing ALL

Researchers say they have developed a technique that can help them determine, at diagnosis, whether children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) will relapse after treatment.

The method involves examining individual leukemia cells using mass cytometry.

In looking at the cells’ stage of development and signaling behavior, the researchers were able to identify a subset of malignant cells that predispose a patient to relapse.

The team described this method, which they termed “developmentally dependent predictor of relapse (DDPR),” in Nature Medicine.

Prior research suggested relapse may be driven by treatment-resistant cells that are present from the beginning of disease development.

“We wondered, can we identify those cells at the time the patient first presents to the clinic, and can we treat patients with a specific therapy to target them?” said study author Kara Davis, DO, of Stanford University in California.

Dr Davis and her colleagues used mass cytometry to analyze diagnostic bone marrow samples from 60 patients with BCP-ALL.

To pinpoint the problematic cells among the millions of cells in each patient’s sample, the researchers had to figure out how to organize the data.

“Every patient has vastly different features to their cancer,” Dr Davis said, “and we had to ask, ‘Is there any common thread between them?’”

The solution, the researchers found, was to match BCP-ALL cells and healthy B cells according to their developmental states, comparing the leukemic cells to the healthy cells.

The comparison revealed 6 features of leukemic cell populations that were associated with relapse.

Broadly, the features suggested that pro-BII cells with activated mTOR signaling were associated with relapse, as were pre-BI cells with activated and unresponsive pre-B-cell receptor signaling.

“We do not understand the mechanisms by which malignant cells from the pro-BII and pre-BI stages of development resist treatment,” Dr Davis noted.

However, she and her colleagues were able to show the leukemic cell features identified by DDPR could predict relapse in the BCP-ALL patients.

Of the 60 patients analyzed, there were 54 with at least 3 years of follow-up. The researchers divided these patients into a training cohort (n=44) and a validation cohort (n=10).

The team used an integrated cumulative/dynamic area under the curve (iAUC) and a C-statistic to assess DDPR performance in both cohorts.

In the training cohort, DDPR had an iAUC value of 0.92 and a C-statistic of 0.87. In the validation cohort, DDPR had an iAUC value of 0.85 and a C-statistic of 0.87.

The researchers also said DDPR “performed well” in predicting relapse-free survival in a retrospective analysis of both cohorts (P = 2.8 × 10⁻⁷).

Now, the researchers plan to validate DDPR in a larger number of patients and evaluate whether the same general approach could predict relapse in other cancers.

Junichi Sugita, MD, PhD

SALT LAKE CITY—New research suggests outcomes may be similar whether patients receive ­myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) prior to haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTCy).

Results from 2 parallel, phase 2 trials showed that MAC­-PTCy­-haploPBSCT and RIC­-PTCy-haplo­PBSCT produced comparable rates of engraftment, acute and chronic graft-versus host disease (GVHD), relapse, and non-relapse mortality (NRM).

Rates of overall survival (OS) and event-free survival (EFS) were significantly higher in the MAC group. However, the fact that some RIC recipients had received prior allogeneic transplants—and none of the MAC recipients had—appeared to play a role in survival outcomes.

Junichi Sugita, MD, PhD, of Hokkaido University in Sapporo, Japan, presented these results at the 2018 BMT Tandem Meetings (abstract 50*).

To compare MAC and RIC in the context of PTCy­-haploPBSCT, Dr Sugita and his colleagues conducted 2 parallel studies—JSCT Haplo 14 MAC and JSCT Haplo 14 RIC.

Patients

There were 50 patients in the MAC trial and 77 in the RIC trial. They had median ages of 36 (range, 17 to 60) and 58 (range, 22 to 65), respectively (P<0.01). There was a greater percentage of male patients among MAC recipients (82% vs 62%, P=0.028).

Diagnoses were similar between the groups and included:

• Acute myeloid leukemia—23 MAC, 34 RIC
• Acute lymphoblastic leukemia—11 MAC, 14 RIC
• Myelodysplastic syndromes/myeloproliferative neoplasms—6 MAC, 12 RIC
• Lymphoma—6 MAC, 14 RIC
• “Other”—4 MAC, 3 RIC.

Forty-eight percent (n=24) of MAC recipients and 58% (n=45) of RIC recipients were not in remission at transplant (P=0.48). There were no significant differences in disease risk index (P=0.34).

Thirty-nine percent of RIC recipients (n=30) had a history of allogeneic transplant, but none of the MAC recipients did (P<0.01).

Conditioning and prophylaxis

There were 2 MAC regimens. One consisted of fludarabine (Flu, 30 mg/m²/day on days -6 to -4) plus total body irradiation (TBI, 12 Gy on days -3 to -1). The other consisted of Flu (30 mg/m²/day on days -6 to -2), busulfan (BU, 3.2 mg/kg/day on days -6 to -3), and TBI (4 Gy on day -1).

The RIC regimen consisted of Flu (30 mg/m²/day on days -6 to -2), BU (3.2 mg/kg/day on days -4 to -3), and TBI (4 Gy on day -1).

All patients received GVHD prophylaxis consisting of cyclophosphamide (50 mg/kg/day on days 3 and 4), tacrolimus (days 5 to 180), and mycophenolate mofetil (days 5 to 60).

Graft

Siblings were the most common donors for MAC recipients (50%, n=25), followed by parents (28%, n=14), children (16%, n=8), and “other” donors (6%, n=3).

Children were the most common donors for RIC recipients (60%, n=46), followed by siblings (33%, n=25), and parents (8%, n=6).

There was no significant difference between MAC and RIC recipients when it came to human leukocyte antigen matching, cytomegalovirus serostatus, or CD34 cell dose.

However, there was a significant difference in donor-recipient gender matching (P=0.033).

Fifty-two percent (n=26) of MAC recipients and 62% (n=48) of RIC recipients had a donor-recipient gender match. Forty-two percent (n=21) and 22% (n=17), respectively, had female donor to male recipient.

Engraftment and GVHD

“Hematopoietic recovery was similar between MAC and RIC,” Dr Sugita said.

The cumulative incidence of neutrophil engraftment was 98% in MAC recipients and 94% in RIC recipients. The median time to neutrophil engraftment was 17 days and 18 days, respectively (P=0.10).

The cumulative incidence of platelet engraftment was 84% in the MAC recipients and 74% in the RIC recipients. The median time to platelet engraftment was 31 days and 37 days, respectively (P=0.32).

“Complete chimerism was achieved in all engrafted patients,” Dr Sugita noted.

There was no significant difference between MAC and RIC recipients when it came to acute or chronic GVHD.

At day 100, the cumulative incidence of grade 2-4 acute GVHD was 18% in the MAC group and 14% in the RIC group (P=0.52). Grade 3-4 acute GVHD was 8% and 5%, respectively (P=0.52).

At 2 years, the cumulative incidence of all-grade chronic GVHD was 36% in the MAC group and 27% in the RIC group (P=0.24). Moderate to severe chronic GVHD was 20% in both groups (P=1.0).

Relapse and survival

There was no significant between-group difference in NRM or relapse.

The cumulative incidence of NRM at 2 years was 20% in the RIC group and 10% in the MAC group (P=0.15). The cumulative incidence of relapse at 2 years was 45% and 36%, respectively (P=0.32).

Survival was superior in the MAC recipients. The 2-year OS was 68% in the MAC group and 44% in the RIC group (P=0.02). The 2-year EFS was 54% and 35%, respectively (P=0.04).

However, survival appeared to be affected by history of allogeneic transplant.

“Patients with a history of prior allogenic SCT have significantly worse overall survival and event-free survival,” Dr Sugita said.

Two-year OS was 31% in RIC recipients with a history of transplant and 52% in RIC recipients without a history of transplant (P=0.04). The OS was 68% in MAC recipients, all of whom had no history of transplant.

Two-year EFS was 21%, 44%, and 54%, respectively (P=0.02 for difference between 2 RIC groups).

In a multivariate analysis, conditioning regimen was not a significant predictor of NRM. The hazard ratio (HR) for RIC was 1.13 (P=0.85).

Likewise, conditioning regimen was not a significant predictor of relapse (HR=0.81, P=0.53), OS (HR=0.85, P=0.66), or EFS (HR=0.73, P=0.34).

“Our results indicate that both MAC and RIC are valid options for PTCy-haplo,” Dr Sugita said in closing.

“Ideally, a more precise comparison of MAC and RIC should be studied further in the setting of, if possible, a randomized trial.” 

*Data in the abstract differs from the presentation.

Junichi Sugita, MD, PhD

SALT LAKE CITY—New research suggests outcomes may be similar whether patients receive ­myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) prior to haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTCy).

Results from 2 parallel, phase 2 trials showed that MAC­-PTCy­-haploPBSCT and RIC­-PTCy-haplo­PBSCT produced comparable rates of engraftment, acute and chronic graft-versus host disease (GVHD), relapse, and non-relapse mortality (NRM).

Rates of overall survival (OS) and event-free survival (EFS) were significantly higher in the MAC group. However, the fact that some RIC recipients had received prior allogeneic transplants—and none of the MAC recipients had—appeared to play a role in survival outcomes.

Junichi Sugita, MD, PhD, of Hokkaido University in Sapporo, Japan, presented these results at the 2018 BMT Tandem Meetings (abstract 50*).

To compare MAC and RIC in the context of PTCy­-haploPBSCT, Dr Sugita and his colleagues conducted 2 parallel studies—JSCT Haplo 14 MAC and JSCT Haplo 14 RIC.

Patients

There were 50 patients in the MAC trial and 77 in the RIC trial. They had median ages of 36 (range, 17 to 60) and 58 (range, 22 to 65), respectively (P<0.01). There was a greater percentage of male patients among MAC recipients (82% vs 62%, P=0.028).

Diagnoses were similar between the groups and included:

• Acute myeloid leukemia—23 MAC, 34 RIC
• Acute lymphoblastic leukemia—11 MAC, 14 RIC
• Myelodysplastic syndromes/myeloproliferative neoplasms—6 MAC, 12 RIC
• Lymphoma—6 MAC, 14 RIC
• “Other”—4 MAC, 3 RIC.

Forty-eight percent (n=24) of MAC recipients and 58% (n=45) of RIC recipients were not in remission at transplant (P=0.48). There were no significant differences in disease risk index (P=0.34).

Thirty-nine percent of RIC recipients (n=30) had a history of allogeneic transplant, but none of the MAC recipients did (P<0.01).

Conditioning and prophylaxis

There were 2 MAC regimens. One consisted of fludarabine (Flu, 30 mg/m²/day on days -6 to -4) plus total body irradiation (TBI, 12 Gy on days -3 to -1). The other consisted of Flu (30 mg/m²/day on days -6 to -2), busulfan (BU, 3.2 mg/kg/day on days -6 to -3), and TBI (4 Gy on day -1).

The RIC regimen consisted of Flu (30 mg/m²/day on days -6 to -2), BU (3.2 mg/kg/day on days -4 to -3), and TBI (4 Gy on day -1).

All patients received GVHD prophylaxis consisting of cyclophosphamide (50 mg/kg/day on days 3 and 4), tacrolimus (days 5 to 180), and mycophenolate mofetil (days 5 to 60).

Graft

Siblings were the most common donors for MAC recipients (50%, n=25), followed by parents (28%, n=14), children (16%, n=8), and “other” donors (6%, n=3).

Children were the most common donors for RIC recipients (60%, n=46), followed by siblings (33%, n=25), and parents (8%, n=6).

There was no significant difference between MAC and RIC recipients when it came to human leukocyte antigen matching, cytomegalovirus serostatus, or CD34 cell dose.

However, there was a significant difference in donor-recipient gender matching (P=0.033).

Fifty-two percent (n=26) of MAC recipients and 62% (n=48) of RIC recipients had a donor-recipient gender match. Forty-two percent (n=21) and 22% (n=17), respectively, had female donor to male recipient.

Engraftment and GVHD

“Hematopoietic recovery was similar between MAC and RIC,” Dr Sugita said.

The cumulative incidence of neutrophil engraftment was 98% in MAC recipients and 94% in RIC recipients. The median time to neutrophil engraftment was 17 days and 18 days, respectively (P=0.10).

The cumulative incidence of platelet engraftment was 84% in the MAC recipients and 74% in the RIC recipients. The median time to platelet engraftment was 31 days and 37 days, respectively (P=0.32).

“Complete chimerism was achieved in all engrafted patients,” Dr Sugita noted.

There was no significant difference between MAC and RIC recipients when it came to acute or chronic GVHD.

At day 100, the cumulative incidence of grade 2-4 acute GVHD was 18% in the MAC group and 14% in the RIC group (P=0.52). Grade 3-4 acute GVHD was 8% and 5%, respectively (P=0.52).

At 2 years, the cumulative incidence of all-grade chronic GVHD was 36% in the MAC group and 27% in the RIC group (P=0.24). Moderate to severe chronic GVHD was 20% in both groups (P=1.0).

Relapse and survival

There was no significant between-group difference in NRM or relapse.

The cumulative incidence of NRM at 2 years was 20% in the RIC group and 10% in the MAC group (P=0.15). The cumulative incidence of relapse at 2 years was 45% and 36%, respectively (P=0.32).

Survival was superior in the MAC recipients. The 2-year OS was 68% in the MAC group and 44% in the RIC group (P=0.02). The 2-year EFS was 54% and 35%, respectively (P=0.04).

However, survival appeared to be affected by history of allogeneic transplant.

“Patients with a history of prior allogenic SCT have significantly worse overall survival and event-free survival,” Dr Sugita said.

Two-year OS was 31% in RIC recipients with a history of transplant and 52% in RIC recipients without a history of transplant (P=0.04). The OS was 68% in MAC recipients, all of whom had no history of transplant.

Two-year EFS was 21%, 44%, and 54%, respectively (P=0.02 for difference between 2 RIC groups).

In a multivariate analysis, conditioning regimen was not a significant predictor of NRM. The hazard ratio (HR) for RIC was 1.13 (P=0.85).

Likewise, conditioning regimen was not a significant predictor of relapse (HR=0.81, P=0.53), OS (HR=0.85, P=0.66), or EFS (HR=0.73, P=0.34).

“Our results indicate that both MAC and RIC are valid options for PTCy-haplo,” Dr Sugita said in closing.

“Ideally, a more precise comparison of MAC and RIC should be studied further in the setting of, if possible, a randomized trial.” 

*Data in the abstract differs from the presentation.

Junichi Sugita, MD, PhD

SALT LAKE CITY—New research suggests outcomes may be similar whether patients receive ­myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) prior to haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTCy).

Results from 2 parallel, phase 2 trials showed that MAC­-PTCy­-haploPBSCT and RIC­-PTCy-haplo­PBSCT produced comparable rates of engraftment, acute and chronic graft-versus host disease (GVHD), relapse, and non-relapse mortality (NRM).

Rates of overall survival (OS) and event-free survival (EFS) were significantly higher in the MAC group. However, the fact that some RIC recipients had received prior allogeneic transplants—and none of the MAC recipients had—appeared to play a role in survival outcomes.

Junichi Sugita, MD, PhD, of Hokkaido University in Sapporo, Japan, presented these results at the 2018 BMT Tandem Meetings (abstract 50*).

To compare MAC and RIC in the context of PTCy­-haploPBSCT, Dr Sugita and his colleagues conducted 2 parallel studies—JSCT Haplo 14 MAC and JSCT Haplo 14 RIC.

Patients

There were 50 patients in the MAC trial and 77 in the RIC trial. They had median ages of 36 (range, 17 to 60) and 58 (range, 22 to 65), respectively (P<0.01). There was a greater percentage of male patients among MAC recipients (82% vs 62%, P=0.028).

Diagnoses were similar between the groups and included:

• Acute myeloid leukemia—23 MAC, 34 RIC
• Acute lymphoblastic leukemia—11 MAC, 14 RIC
• Myelodysplastic syndromes/myeloproliferative neoplasms—6 MAC, 12 RIC
• Lymphoma—6 MAC, 14 RIC
• “Other”—4 MAC, 3 RIC.

Forty-eight percent (n=24) of MAC recipients and 58% (n=45) of RIC recipients were not in remission at transplant (P=0.48). There were no significant differences in disease risk index (P=0.34).

Thirty-nine percent of RIC recipients (n=30) had a history of allogeneic transplant, but none of the MAC recipients did (P<0.01).

Conditioning and prophylaxis

There were 2 MAC regimens. One consisted of fludarabine (Flu, 30 mg/m²/day on days -6 to -4) plus total body irradiation (TBI, 12 Gy on days -3 to -1). The other consisted of Flu (30 mg/m²/day on days -6 to -2), busulfan (BU, 3.2 mg/kg/day on days -6 to -3), and TBI (4 Gy on day -1).

The RIC regimen consisted of Flu (30 mg/m²/day on days -6 to -2), BU (3.2 mg/kg/day on days -4 to -3), and TBI (4 Gy on day -1).

All patients received GVHD prophylaxis consisting of cyclophosphamide (50 mg/kg/day on days 3 and 4), tacrolimus (days 5 to 180), and mycophenolate mofetil (days 5 to 60).

Graft

Siblings were the most common donors for MAC recipients (50%, n=25), followed by parents (28%, n=14), children (16%, n=8), and “other” donors (6%, n=3).

Children were the most common donors for RIC recipients (60%, n=46), followed by siblings (33%, n=25), and parents (8%, n=6).

There was no significant difference between MAC and RIC recipients when it came to human leukocyte antigen matching, cytomegalovirus serostatus, or CD34 cell dose.

However, there was a significant difference in donor-recipient gender matching (P=0.033).

Fifty-two percent (n=26) of MAC recipients and 62% (n=48) of RIC recipients had a donor-recipient gender match. Forty-two percent (n=21) and 22% (n=17), respectively, had female donor to male recipient.

Engraftment and GVHD

“Hematopoietic recovery was similar between MAC and RIC,” Dr Sugita said.

The cumulative incidence of neutrophil engraftment was 98% in MAC recipients and 94% in RIC recipients. The median time to neutrophil engraftment was 17 days and 18 days, respectively (P=0.10).

The cumulative incidence of platelet engraftment was 84% in the MAC recipients and 74% in the RIC recipients. The median time to platelet engraftment was 31 days and 37 days, respectively (P=0.32).

“Complete chimerism was achieved in all engrafted patients,” Dr Sugita noted.

There was no significant difference between MAC and RIC recipients when it came to acute or chronic GVHD.

At day 100, the cumulative incidence of grade 2-4 acute GVHD was 18% in the MAC group and 14% in the RIC group (P=0.52). Grade 3-4 acute GVHD was 8% and 5%, respectively (P=0.52).

At 2 years, the cumulative incidence of all-grade chronic GVHD was 36% in the MAC group and 27% in the RIC group (P=0.24). Moderate to severe chronic GVHD was 20% in both groups (P=1.0).

Relapse and survival

There was no significant between-group difference in NRM or relapse.

The cumulative incidence of NRM at 2 years was 20% in the RIC group and 10% in the MAC group (P=0.15). The cumulative incidence of relapse at 2 years was 45% and 36%, respectively (P=0.32).

Survival was superior in the MAC recipients. The 2-year OS was 68% in the MAC group and 44% in the RIC group (P=0.02). The 2-year EFS was 54% and 35%, respectively (P=0.04).

However, survival appeared to be affected by history of allogeneic transplant.

“Patients with a history of prior allogenic SCT have significantly worse overall survival and event-free survival,” Dr Sugita said.

Two-year OS was 31% in RIC recipients with a history of transplant and 52% in RIC recipients without a history of transplant (P=0.04). The OS was 68% in MAC recipients, all of whom had no history of transplant.

Two-year EFS was 21%, 44%, and 54%, respectively (P=0.02 for difference between 2 RIC groups).

In a multivariate analysis, conditioning regimen was not a significant predictor of NRM. The hazard ratio (HR) for RIC was 1.13 (P=0.85).

Likewise, conditioning regimen was not a significant predictor of relapse (HR=0.81, P=0.53), OS (HR=0.85, P=0.66), or EFS (HR=0.73, P=0.34).

“Our results indicate that both MAC and RIC are valid options for PTCy-haplo,” Dr Sugita said in closing.

“Ideally, a more precise comparison of MAC and RIC should be studied further in the setting of, if possible, a randomized trial.” 

*Data in the abstract differs from the presentation.

Photo by George Hodan

Pharmacokinetic (PK) dosing software intended for use in patients with hemophilia A is now available in the US.

This free, web-based, prescription software—myPKFiT for ADVATE—is intended to aid healthcare professionals in personalizing the dose and schedule of ADVATE, a full-length recombinant factor VIII product.

The software was cleared by the US Food and Drug Administration (FDA) for use in hemophilia A patients age 16 and older who weigh at least 45 kg and are receiving prophylaxis with ADVATE.

The myPKFiT software generates ADVATE dosage amount and frequency recommendations using a patient’s age and body weight information, as well as local laboratory factor VIII one-stage clotting activity measurements of sparse samples collected from the patient.

A minimum of 2 sparse sampling points are required at the recommended 3 to 4 hours (± 30 minutes) and at 24 to 32 hours (±1 hour) post-infusion.

The software output may be used to guide ADVATE use to maintain factor VIII activity levels at or above a user-specified minimum of 1% to 3% above natural baseline, in accordance with the FDA-approved dosing recommendations for ADVATE.

myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADVATE.

The software should not be used for patients who have developed neutralizing antibodies to factor VIII products and is not indicated for use in patients with von Willebrand disease.

“A version of myPKFiT has already been widely adopted in Europe since 2014, and we’ve seen how important it has been in helping physicians develop personalized dosing regimens tailored to the specific needs of their patients,” said Andreas Busch, global head of research and development at Shire, the company behind myPKFiT for ADVATE.

“As part of our commitment to precision medicine, we are pleased to bring this innovative application to physicians and patients in the United States.”

More information on the myPKFiT software is available on the ADVATE website and the myPKFiT site.

Photo by George Hodan

Pharmacokinetic (PK) dosing software intended for use in patients with hemophilia A is now available in the US.

This free, web-based, prescription software—myPKFiT for ADVATE—is intended to aid healthcare professionals in personalizing the dose and schedule of ADVATE, a full-length recombinant factor VIII product.

The software was cleared by the US Food and Drug Administration (FDA) for use in hemophilia A patients age 16 and older who weigh at least 45 kg and are receiving prophylaxis with ADVATE.

The myPKFiT software generates ADVATE dosage amount and frequency recommendations using a patient’s age and body weight information, as well as local laboratory factor VIII one-stage clotting activity measurements of sparse samples collected from the patient.

A minimum of 2 sparse sampling points are required at the recommended 3 to 4 hours (± 30 minutes) and at 24 to 32 hours (±1 hour) post-infusion.

The software output may be used to guide ADVATE use to maintain factor VIII activity levels at or above a user-specified minimum of 1% to 3% above natural baseline, in accordance with the FDA-approved dosing recommendations for ADVATE.

myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADVATE.

The software should not be used for patients who have developed neutralizing antibodies to factor VIII products and is not indicated for use in patients with von Willebrand disease.

“A version of myPKFiT has already been widely adopted in Europe since 2014, and we’ve seen how important it has been in helping physicians develop personalized dosing regimens tailored to the specific needs of their patients,” said Andreas Busch, global head of research and development at Shire, the company behind myPKFiT for ADVATE.

“As part of our commitment to precision medicine, we are pleased to bring this innovative application to physicians and patients in the United States.”

More information on the myPKFiT software is available on the ADVATE website and the myPKFiT site.

Photo by George Hodan

Pharmacokinetic (PK) dosing software intended for use in patients with hemophilia A is now available in the US.

This free, web-based, prescription software—myPKFiT for ADVATE—is intended to aid healthcare professionals in personalizing the dose and schedule of ADVATE, a full-length recombinant factor VIII product.

The software was cleared by the US Food and Drug Administration (FDA) for use in hemophilia A patients age 16 and older who weigh at least 45 kg and are receiving prophylaxis with ADVATE.

The myPKFiT software generates ADVATE dosage amount and frequency recommendations using a patient’s age and body weight information, as well as local laboratory factor VIII one-stage clotting activity measurements of sparse samples collected from the patient.

A minimum of 2 sparse sampling points are required at the recommended 3 to 4 hours (± 30 minutes) and at 24 to 32 hours (±1 hour) post-infusion.

The software output may be used to guide ADVATE use to maintain factor VIII activity levels at or above a user-specified minimum of 1% to 3% above natural baseline, in accordance with the FDA-approved dosing recommendations for ADVATE.

myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADVATE.

The software should not be used for patients who have developed neutralizing antibodies to factor VIII products and is not indicated for use in patients with von Willebrand disease.

“A version of myPKFiT has already been widely adopted in Europe since 2014, and we’ve seen how important it has been in helping physicians develop personalized dosing regimens tailored to the specific needs of their patients,” said Andreas Busch, global head of research and development at Shire, the company behind myPKFiT for ADVATE.

“As part of our commitment to precision medicine, we are pleased to bring this innovative application to physicians and patients in the United States.”

More information on the myPKFiT software is available on the ADVATE website and the myPKFiT site.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.