Clinical Edge Journal Scan Commentary

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

In almost 80% of cases, cutaneous psoriasis predates the onset of arthritic psoriasis. Therefore, identifying risk factors for the development of psoriatic arthritis (PsA) in patients with skin psoriasis is of significant clinical and research interest. One such risk factor that has previous been described is the severity of psoriasis. In a prospective population-based cohort study performed within The Health Improvement Network in the UK, Ogdie et al demonstrated that in a cohort of 8881 patients aged 25–60 years with a code for psoriasis randomly selected between 2008 and 2011, the extent of psoriasis as measured by the body surface area affected (BSA) was a strong predictor of developing PsA. Comorbidities, such as obesity and depression, were additive risk factors. In this cohort, after a mean follow-up time of 4.2 years (SD 2.1), the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA > 10% [hazard ratio (HR) 2.01, 95% CI 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI 1.02, 2.03), obesity (HR 1.64, 95% CI 1.19, 2.26) and depression (HR 1.68, 95% CI 1.21, 2.33) were associated with incident PsA. Thus, patients with these risk factors should be carefully evaluated at each visit for signs of PsA.

One important question is whether treatment of psoriasis with targeted therapies reduces the risk of incident PsA. In a retrospective cohort study using the electronic medical records of the Maccabi Healthcare Services in Israel, Rosenthal et al, using propensity score matching compared patients who had received biological treatment for psoriasis and were not diagnosed with PsA before or at the time of biologic treatment initiation to controls not on such treatment. Patients were matched by age at diagnosis, gender, time until treatment initiation, maximum body mass index (BMI), and smoking. Multivariable Cox regression analysis showed that the control group had a significantly higher risk for PsA compared to patients treated with biologics (adjusted HR 1.39; 95%CI 1.03-1.87). Thus, there is increasing evidence that biologic therapy may decrease the risk of developing PsA.

Management of comorbidities remain an ongoing challenge in the management of psoriatic disease. In a cross-sectional multi-center study conducted by the Turkish League Against Rheumatism involving 1033 patients with PsA, 383 (37.1%) of whom were obese, Gok et al report that obesity was significantly associated with higher disease activity, lower quality of life scores, anxiety, depression, and fatigue. Comorbidities including obesity must be addressed for holistic management of PsA.

But counseling about modifiable risk factors remains low. Taylor et al reported that counseling or education for modifiable lifestyle risk factors were rare during psoriatic disease outpatient visits. Using data from the National Ambulatory Medical Care Survey (2002-2016) and the National Hospital Ambulatory Medical Care Survey (2002-2011) conducted in the United States, they demonstrate low rates of counseling for any modifiable lifestyle risk factor (11.1%; 95% CI 7.9%-15.3%), tobacco (4.8%; 95% CI 2.8%-8.0%), and obesity (2.8%; 95% CI 1.7%-4.5%). Thus, in addition to counseling about medications, an effort must be made to counsel about modifiable risk factors and comorbidities to improve quality of life of patients with psoriatic disease.

References

Ogdie A, Shin DB, Love TJ, Gelfand JM. Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study. Rheumatology (Oxf). 2021:Sep 11:keab622 (in press). doi: 10.1093/rheumatology/keab622 PMID: 34508558.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Shalev Rosenthal Y, Schwartz N, Sagy I, Pavlovsky L. Psoriatic arthritis incidence among patients receiving biologic medications for psoriasis: A nested case control study. Arthritis Rheumatol. 2021:Aug 23. doi: 10.1002/art.41946. Epub ahead of print. PMID: 34423909.

Gok K, Nas K, Tekeoglu I, Sunar I, Keskin Y, Kilic E, Sargin B, Acer Kasman S, Alkan H, Sahin N, Cengiz G, Cuzdan N, Albayrak Gezer İ, Keskin D, Mulkoglu C, Resorlu H, Bal A, Duruoz MT, Kucukakkas O, Yurdakul OV, Alkan Melikoglu M, Aydin Y, Ayhan FF, Bodur H, Calis M, Capkin E, Devrimsel G, Ecesoy H, Hizmetli S, Kamanli A, Kutluk O, Sen N, Sendur OF, Tolu S, Toprak M, Tuncer T. Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study. Rheumatol Int. 2021:Aug 28. doi: 10.1007/s00296-021-04971-8. Epub ahead of print. PMID: 34453579.

Taylor MT, Keller M, Barbieri JS. Lifestyle risk factor counseling at visits for psoriasis and psoriatic arthritis in the United States. J Am Acad Dermatol. 2021:Aug 25:S0190-9622(21)02376-8. doi: 10.1016/j.jaad.2021.08.034. Epub ahead of print. PMID: 34450204

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Cigarette smoking is a well-known modifiable risk factor for the development of rheumatoid arthritis (RA). Studies have suggested not only an elevated risk but possible pathogenetic role in the development of autoantibodies, as well as effects on disease outcomes. Passive cigarette smoking has also been proposed as a potential risk factor for RA, though studies are harder to evaluate. This review of prospective data from the Nurses Health Study (NHS) by Yoshida et al looks at incident RA among women enrolled in the study and the influence of in utero, childhood, and adulthood exposure to cigarettes. Childhood exposure to parental smoking was associated with seropositive RA (hazard ratio 1.75) even after controlling for adult personal smoking, and maternal smoking during pregnancy was associated with RA, though the latter effect was not seen after controlling for subsequent smoking exposure. As the authors point out, verifiable prospective data is difficult to obtain regarding exposure to smoking in utero or in childhood and recall bias is possible in obtaining historical information in this prospective study given the use of questionnaires, though it remains plausible given prior studies on the association of personal smoking with RA.

The involvement of gut microbiota in development of autoimmunity has also been postulated but not well-explained. Several recent studies have examined the impact of antibiotic use on the development of RA, including a recent large UK-based case-control study suggesting an increase in RA incidence in people with antibiotic exposure. While a systematic review is ongoing, this prospective cohort study by Liu et al also examines data from NHSI and NHSII and RA risk in patients exposed to antibiotics, stratified by duration of use (none, ≤14 days, ≥15 days). It is reassuring that in this study neither short term (≤14 days) nor long term (≥15 days) antibiotic use was associated with RA risk. Comparison with prior studies with prescription data, however, is limited given the use of questionnaires to establish duration of recent antibiotic exposure.

Fatigue is a common symptom of RA and has a high impact on quality of life in terms of function. The study by Holten et al examines data from the ARCTIC trial in terms of associations between disease activity and fatigue in early RA, as well as change in fatigue with therapy for RA. Fatigue was measured via a visual analog scale (VAS) and did decrease with therapy from baseline; 80% of patients in the study had moderate or high disease activity based on disease activity score (DAS) at baseline and 69% of patients reported fatigue, while 9% of patients had moderate or high disease activity based on DAS at  24 months and 38% reported fatigue. Interestingly, patients who were in remission (per DAS) at 6 months had a reduced risk of fatigue at 24 months. It is hard to interpret this information in a granular way as fatigue is not measured in a standardized way across clinical studies and the only instrument of measure in the ARCTIC trial was the VAS. An alternate view, for example examining the impact of baseline fatigue on response to therapy, may also be reasonable, or fatigue may be a residual symptom similar to chronic myofascial or “non-inflammatory” pain not responsive to treatment in RA.

Finally, another associated extra-articular manifestation of RA is bronchiectasis. Martin et al performed a systematic review and meta-analysis of the literature and found that the prevalence of bronchiectasis was about 18% in RA patients, suggesting that it is more common than previously thought. However, inclusion of CT imaging may detect subclinical bronchiectasis and other secondary causes were not determined. Still, given the effects on quality of life and mortality, further research into causes and risk factors for bronchiectasis in RA is warranted.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Latin American countries have a high rate of SARS-CoV-2 infection and some of the highest COVID-19 deaths worldwide. Brazil, Colombia, Argentina, and Mexico have reported the highest number of confirmed cases. More recently has been reported that in series form US and Europe the mortality of COVID-19 has not been as high as reported in other hematological conditions and the response to vaccination also has bene described as high. In a recent report, Pagnano et al. (Leuk Lymphoma. 2021) has recently reported the clinical evolution and outcome of COVID-19 in patients with chronic myeloid leukemia in Latin America. In an observational multicenter study with a total of 92 patients with COVID-19 between March and December 2020 with 26% of whom were severe or critical. Eighty-one patients recovered (88%), and 11 (11.9%) died from COVID-19. Almost half of them had at least one comorbidity. Patients with a major molecular response presented superior overall survival compared to patients with no major molecular response (91 vs. 61%, respectively; P = 0.004). Patients in treatment-free remission and receiving tyrosine kinase inhibitors showed higher survival rates (100 and 89%) than patients who underwent hematopoietic stem cell transplantation and those who did not receive tyrosine kinase inhibitors (50 and 33%).

Currently the most common reason for TKI discontinuation is intolerance. Ma et al (Leuk Res. 2021) reports the long-term outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4–90.6 %). However, amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2–80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Patients who switch for intolerance continue to enjoy excellent long term clinical outcomes.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond.  Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of  patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was  better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.

Our first study comes out of Sheffield, UK, and Halle, Germany, and looks at the correlation between sarcopenia and EPI (Jalal et al). Notably sarcopenia, or reduction in muscle mass, is a known complication of malnutrition and conditions like EPI. It has traditionally been difficult to diagnose because traditional methods have suffered from low accuracy (i.e., mid-arm circumference). In recent years, commercially available software has been developed to digitally assess skeletal muscle mass on axial CT imaging. Digital imaging allows for granular assessments of metrics such as myosteatosis and sacropenic obesity, both of which remained relatively elusive metrics in prior ways of assessing sarcopenia.

In this study, researchers postulate that, since CT scans are recently performed in the evaluation of those patients with suspected pancreatic pathology, it would be natural to assess for sarcopenia on said CT imaging. Identifying sarcopenia might allow clinicians to identify those patients with or at risk for EPI.

Patients referred to EUS for suspected pancreatic pathology were included in the study (except those found to have pancreatic cancer). This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain. Fecal elastase testing was used to determine those with EPI, and digital CT analysis was used to recognize patients with sarcopenia.

Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs. 37.55%; P < .003), myosteatosis (52.2% vs. 10.7%; P = .046), and sarcopenic obesity (66.7% vs. 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI. The authors conclude that digital skeletal mass analysis can be performed on patients already undergoing CT scans for suspected pancreatic pathology for possible further diagnosis, risk assessment and to better inform clinical management.

Another notable study came out of Baylor College of Medicine that looked at the clinical significance of fatty pancreas (FP) (Krill et al). Diffuse echogenicity of the pancreas is a common finding on endoscopic ultrasound (EUS), but of unknown clinical significance. Krill’s group aimed to determine if diffuse fatty infiltration of the pancreas had any clinical implication on pancreatic function. They conducted a retrospective case-control study comparing adult patients with diffuse echogenicity of the pancreas to those without known pancreatic disease with chronic diarrhea. Notably, the incidence of EPI (47% vs. 6%) and chronic pancreatitis (18% vs. 0%) was significantly higher (both P < .001) in the fatty pancreas group vs. the control group. 

The authors conclude “Our findings suggest that FP may not merely be a benign sonographic finding, but rather imply underlying parenchymal dysfunction, such as that seen when fat deposition occurs in the liver (i.e., nonalcoholic fatty liver disease).” Additionally the paper states that recent literature has found an association between fatty pancreas and increasing body mass index (BMI), hyperlipidemia, insulin resistance, and metabolic syndrome. Perhaps we will further appreciate the likely prominent and under-appreciated role of metabolic syndrome in the development of acute and chronic pancreatitis.

References:

Jalal M, Rosendahl J, Campbell JA, Vinayagam R, Al-Mukhtar A, Hopper AD. Identification of “digital sarcopenia” can aid the detection of pancreatic exocrine insufficiency and malnutrition assessment in patients with suspected pancreatic pathology. Dig Dis 2021 (Jun 8), (in press).

Krill JT, Szafron D, Elhanafi S, et al. Endoscopic ultrasound finding of diffuse echogenicity in the pancreas, is it relevant? Dig Dis Sci 2021 (Aug 4), (in press).

Our first study comes out of Sheffield, UK, and Halle, Germany, and looks at the correlation between sarcopenia and EPI (Jalal et al). Notably sarcopenia, or reduction in muscle mass, is a known complication of malnutrition and conditions like EPI. It has traditionally been difficult to diagnose because traditional methods have suffered from low accuracy (i.e., mid-arm circumference). In recent years, commercially available software has been developed to digitally assess skeletal muscle mass on axial CT imaging. Digital imaging allows for granular assessments of metrics such as myosteatosis and sacropenic obesity, both of which remained relatively elusive metrics in prior ways of assessing sarcopenia.

In this study, researchers postulate that, since CT scans are recently performed in the evaluation of those patients with suspected pancreatic pathology, it would be natural to assess for sarcopenia on said CT imaging. Identifying sarcopenia might allow clinicians to identify those patients with or at risk for EPI.

Patients referred to EUS for suspected pancreatic pathology were included in the study (except those found to have pancreatic cancer). This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain. Fecal elastase testing was used to determine those with EPI, and digital CT analysis was used to recognize patients with sarcopenia.

Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs. 37.55%; P < .003), myosteatosis (52.2% vs. 10.7%; P = .046), and sarcopenic obesity (66.7% vs. 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI. The authors conclude that digital skeletal mass analysis can be performed on patients already undergoing CT scans for suspected pancreatic pathology for possible further diagnosis, risk assessment and to better inform clinical management.

Another notable study came out of Baylor College of Medicine that looked at the clinical significance of fatty pancreas (FP) (Krill et al). Diffuse echogenicity of the pancreas is a common finding on endoscopic ultrasound (EUS), but of unknown clinical significance. Krill’s group aimed to determine if diffuse fatty infiltration of the pancreas had any clinical implication on pancreatic function. They conducted a retrospective case-control study comparing adult patients with diffuse echogenicity of the pancreas to those without known pancreatic disease with chronic diarrhea. Notably, the incidence of EPI (47% vs. 6%) and chronic pancreatitis (18% vs. 0%) was significantly higher (both P < .001) in the fatty pancreas group vs. the control group. 

The authors conclude “Our findings suggest that FP may not merely be a benign sonographic finding, but rather imply underlying parenchymal dysfunction, such as that seen when fat deposition occurs in the liver (i.e., nonalcoholic fatty liver disease).” Additionally the paper states that recent literature has found an association between fatty pancreas and increasing body mass index (BMI), hyperlipidemia, insulin resistance, and metabolic syndrome. Perhaps we will further appreciate the likely prominent and under-appreciated role of metabolic syndrome in the development of acute and chronic pancreatitis.

References:

Jalal M, Rosendahl J, Campbell JA, Vinayagam R, Al-Mukhtar A, Hopper AD. Identification of “digital sarcopenia” can aid the detection of pancreatic exocrine insufficiency and malnutrition assessment in patients with suspected pancreatic pathology. Dig Dis 2021 (Jun 8), (in press).

Krill JT, Szafron D, Elhanafi S, et al. Endoscopic ultrasound finding of diffuse echogenicity in the pancreas, is it relevant? Dig Dis Sci 2021 (Aug 4), (in press).

Our first study comes out of Sheffield, UK, and Halle, Germany, and looks at the correlation between sarcopenia and EPI (Jalal et al). Notably sarcopenia, or reduction in muscle mass, is a known complication of malnutrition and conditions like EPI. It has traditionally been difficult to diagnose because traditional methods have suffered from low accuracy (i.e., mid-arm circumference). In recent years, commercially available software has been developed to digitally assess skeletal muscle mass on axial CT imaging. Digital imaging allows for granular assessments of metrics such as myosteatosis and sacropenic obesity, both of which remained relatively elusive metrics in prior ways of assessing sarcopenia.

In this study, researchers postulate that, since CT scans are recently performed in the evaluation of those patients with suspected pancreatic pathology, it would be natural to assess for sarcopenia on said CT imaging. Identifying sarcopenia might allow clinicians to identify those patients with or at risk for EPI.

Patients referred to EUS for suspected pancreatic pathology were included in the study (except those found to have pancreatic cancer). This prospective study included 102 patients with suspected or proven benign pancreatic pathology, chronic pancreatitis, or recurrent pancreatic type pain. Fecal elastase testing was used to determine those with EPI, and digital CT analysis was used to recognize patients with sarcopenia.

Overall, EPI was present in 45.1% of patients. The prevalence of sarcopenia (67.4% vs. 37.55%; P < .003), myosteatosis (52.2% vs. 10.7%; P = .046), and sarcopenic obesity (66.7% vs. 24.3%; P = .002) was significantly higher in patients with vs without EPI. Sarcopenia (odds ratio [OR], 4.8; P = .02) was strongly associated with EPI. The authors conclude that digital skeletal mass analysis can be performed on patients already undergoing CT scans for suspected pancreatic pathology for possible further diagnosis, risk assessment and to better inform clinical management.

Another notable study came out of Baylor College of Medicine that looked at the clinical significance of fatty pancreas (FP) (Krill et al). Diffuse echogenicity of the pancreas is a common finding on endoscopic ultrasound (EUS), but of unknown clinical significance. Krill’s group aimed to determine if diffuse fatty infiltration of the pancreas had any clinical implication on pancreatic function. They conducted a retrospective case-control study comparing adult patients with diffuse echogenicity of the pancreas to those without known pancreatic disease with chronic diarrhea. Notably, the incidence of EPI (47% vs. 6%) and chronic pancreatitis (18% vs. 0%) was significantly higher (both P < .001) in the fatty pancreas group vs. the control group. 

The authors conclude “Our findings suggest that FP may not merely be a benign sonographic finding, but rather imply underlying parenchymal dysfunction, such as that seen when fat deposition occurs in the liver (i.e., nonalcoholic fatty liver disease).” Additionally the paper states that recent literature has found an association between fatty pancreas and increasing body mass index (BMI), hyperlipidemia, insulin resistance, and metabolic syndrome. Perhaps we will further appreciate the likely prominent and under-appreciated role of metabolic syndrome in the development of acute and chronic pancreatitis.

References:

Jalal M, Rosendahl J, Campbell JA, Vinayagam R, Al-Mukhtar A, Hopper AD. Identification of “digital sarcopenia” can aid the detection of pancreatic exocrine insufficiency and malnutrition assessment in patients with suspected pancreatic pathology. Dig Dis 2021 (Jun 8), (in press).

Krill JT, Szafron D, Elhanafi S, et al. Endoscopic ultrasound finding of diffuse echogenicity in the pancreas, is it relevant? Dig Dis Sci 2021 (Aug 4), (in press).

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.

Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al  conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.

One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al  reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Chiuve et al published a large cohort study in the Journal of Epidemiology and Community Health that evaluated the association between uterine fibroids and diagnosed depression, anxiety and self-directed violence. Women aged 18-50 years with diagnosed uterine fibroids (n=313,754) were identified in the Optum Clinformatics commercial insurance claims database and matched 1:2 on age and calendar time to women without (n=627,539). After adjusting for confounders, women with uterine fibroids had a higher rate of depression, anxiety and self-directed violence then women not diagnosed with fibroids. Among women with pain symptoms and heavy menstrual bleeding, the hazard ratio comparing women with fibroids to women without was 1.21 for depression, 1.18 for anxiety and 1.68 for self-directed violence. Among women with fibroids, those who underwent hysterectomy had higher rates of depression, anxiety and self-directed violence.

A third study by Wesselink et al in Human Reproduction examined ambient air pollution exposure and the risk of developing uterine fibroids. This was a prospective cohort study of 21,998 premenopausal Black women in 56 US metropolitan areas from 1997 to 2011. During the follow up, 28.4% of participants (n=6238) reported uterine fibroid diagnosis by ultrasound or surgery. Increased ozone concentrations were associated with an increased risk of being diagnosed with uterine fibroids, with a stronger association among women less than 35 years of age and parous women. Other pollutants, specifically particulate matter <2.5 microns and nitrogen dioxide, were not associated with an increased risk of uterine fibroids.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.