We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

We are excited to announce a new partnership between Cutis and the Association of Professors of Dermatology Residency Program Directors Section (APD-RPDS). The new APD-RPDS column Residency Roundup will contain quarterly communications and submissions that we hope will facilitate greater dissemination of information that is useful to the dermatology teaching community.

The APD is a group of academic dermatologists whose membership comprises chairs, chiefs, residency and fellowship program directors, and teaching faculty. Each fall, the group convenes in Chicago, Illinois, for a 2-day meeting centered around departmental and program leadership with a focus on education. The APD-RPDS was formed in 2020 and is led by a steering committee of 9 members, including our current Chair, Ilana S. Rosman, MD (Washington University School of Medicine, St. Louis, Missouri), and Vice Chair, Jo-Ann M. Latkowski, MD (New York University, New York). Committee members are elected from and by the APD membership and must serve in program leadership at their home programs. The APD-RPDS helps plan and coordinate breakout sessions and lectures at the annual APD meeting, which typically relate to program director duties, changing policies within the American Board of Dermatology or Accreditation Council for Graduate Medical Education, ideas for future growth, and changes in our specialty and in resident education. Members of the APD-RPDS have access to the APD listserv, a valuable resource for discussing issues affecting residency training. We also have work groups led by our members, which include diversity, equity, and inclusion; resource development; communications; and the annual survey. To join the APD, the RPDS, and/or any of our workgroups, please reach out to us or visit the APD website (https://www.dermatologyprofessors.org).

We look forward to welcoming and expediently reviewing members’ submissions to the new Residency Roundup column falling into 2 principal categories within the scope of dermatologic recruitment, didactic education, and clinical training. The first category will feature novel tools, programs, and platforms to improve dermatology training through collaboration. This could entail a description of a new platform designed for sharing resources among programs and specialties to enhance learning for trainees and faculty alike. For example, if a database is created that contains prerecorded lectures pertaining to alopecia, a potential article submission might introduce the database and provide information on what topics are covered and how to access these lectures for readers worldwide. Likewise, if a new technology emerges that allows for easier collaboration among programs, a possible submission would introduce the technology and discuss its potential benefits to trainees, faculty, and practicing dermatologists.

Secondly and more commonly, we anticipate the Residency Roundup column will feature articles that delve into the critical issues and challenges currently impacting recruitment, training, and administration in dermatology residency programs. Specific topics may include but are not limited to recruitment of underrepresented in medicine applicants to dermatology, technological advances to improve teaching methods within training programs, surveys delving into the dermatology match process, and educational gaps or future directions in the specialty. The column occasionally may be used to disseminate information from our section of the APD, including consensus statements or editorials related to changes implemented in the dermatology residency application process. A prospective editorial on this subject could explore varying viewpoints of implemented and proposed changes as well as the reasons behind the changes.

Our group is collaborative, and our aim is to improve education, equity, management of program director responsibilities, and the dermatology application process for programs and applicants alike. With your input, experience, and varied perspectives, we look forward to moving the field of dermatology to a better future by working together. 

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.

A recent American Gastroenterological Association Clinical Practice Update for evaluation and management of gastroesophageal reflux disease (GERD) focuses on delivering personalized diagnostic and therapeutic strategies.

The document includes new advice on use of upfront objective testing for isolated extraesophageal symptoms, confirmation of GERD diagnosis prior to long-term GERD therapy even in PPI responders, as well as important elements focused on personalization of therapy.

Tharakorn/Getty Images

Although GERD is common, with an estimated 30% of people in the United States experiencing symptoms, up to half of all individuals on proton pump inhibitor (PPI) therapy report incomplete symptom improvement. That could be due to the heterogeneous nature of symptoms, which may include heartburn and regurgitation, chest pain, and cough or sore throat, among others. Other conditions may produce similar symptoms or could be exacerbated by the presence of GERD.

The authors of the expert review, published in Clinical Gastroenterology and Hepatology, note that these considerations have driven increased interest in personalized approaches to the management of GERD. The practice update includes sections on how to approach GERD symptoms in the clinic, personalized diagnosis related to GERD symptoms, and precision management.

In the initial management, the authors offer advice on involving the patient in creating a care plan, patient education, and conducting a 4- to 8-week PPI trial in patients with heartburn, regurgitation, or noncardiac chest pains without accompanying alarm signals. If symptoms don’t improve to the patient’s satisfaction, dosing can be boosted to twice per day, or a more effective acid suppressor can be substituted and continued at a once-daily dose. When the response to PPIs is adequate, the dose should be reduced until the lowest effective dose is reached, or the patient could potentially be moved to H2 receptor antagonists or other antacids. However, patients with erosive esophagitis, biopsy-confirmed Barrett’s esophagus, or peptic stricture must stay on long-term PPI therapy.

The authors also gave advice on when to conduct objective testing. When a PPI trial doesn’t adequately address troublesome heartburn, regurgitation, and/or noncardiac chest pain, or if alarm systems are present, endoscopy should be employed to look for erosive reflux disease or long-segment Barrett’s esophagus as conclusive evidence for GERD. If these are absent, prolonged wireless pH monitoring while a patient is off medication is suggested. In addition, patients with extraesophageal symptoms suspected to be caused by reflux should undergo upfront objective reflux testing while off PPI therapy rather than doing an empiric PPI trial.

The authors advise that, if patients don’t have proven GERD and are continued on PPI therapy, they should be evaluated within 12 months to ensure that the therapy and dose are appropriate. Physicians should offer endoscopy with prolonged wireless reflux monitoring in the absence of PPI therapy (ideally after 2-4 weeks of withdrawal) to confirm that long-term PPI therapy is needed.

A recent American Gastroenterological Association Clinical Practice Update for evaluation and management of gastroesophageal reflux disease (GERD) focuses on delivering personalized diagnostic and therapeutic strategies.

The document includes new advice on use of upfront objective testing for isolated extraesophageal symptoms, confirmation of GERD diagnosis prior to long-term GERD therapy even in PPI responders, as well as important elements focused on personalization of therapy.

Tharakorn/Getty Images

Although GERD is common, with an estimated 30% of people in the United States experiencing symptoms, up to half of all individuals on proton pump inhibitor (PPI) therapy report incomplete symptom improvement. That could be due to the heterogeneous nature of symptoms, which may include heartburn and regurgitation, chest pain, and cough or sore throat, among others. Other conditions may produce similar symptoms or could be exacerbated by the presence of GERD.

The authors of the expert review, published in Clinical Gastroenterology and Hepatology, note that these considerations have driven increased interest in personalized approaches to the management of GERD. The practice update includes sections on how to approach GERD symptoms in the clinic, personalized diagnosis related to GERD symptoms, and precision management.

In the initial management, the authors offer advice on involving the patient in creating a care plan, patient education, and conducting a 4- to 8-week PPI trial in patients with heartburn, regurgitation, or noncardiac chest pains without accompanying alarm signals. If symptoms don’t improve to the patient’s satisfaction, dosing can be boosted to twice per day, or a more effective acid suppressor can be substituted and continued at a once-daily dose. When the response to PPIs is adequate, the dose should be reduced until the lowest effective dose is reached, or the patient could potentially be moved to H2 receptor antagonists or other antacids. However, patients with erosive esophagitis, biopsy-confirmed Barrett’s esophagus, or peptic stricture must stay on long-term PPI therapy.

The authors also gave advice on when to conduct objective testing. When a PPI trial doesn’t adequately address troublesome heartburn, regurgitation, and/or noncardiac chest pain, or if alarm systems are present, endoscopy should be employed to look for erosive reflux disease or long-segment Barrett’s esophagus as conclusive evidence for GERD. If these are absent, prolonged wireless pH monitoring while a patient is off medication is suggested. In addition, patients with extraesophageal symptoms suspected to be caused by reflux should undergo upfront objective reflux testing while off PPI therapy rather than doing an empiric PPI trial.

The authors advise that, if patients don’t have proven GERD and are continued on PPI therapy, they should be evaluated within 12 months to ensure that the therapy and dose are appropriate. Physicians should offer endoscopy with prolonged wireless reflux monitoring in the absence of PPI therapy (ideally after 2-4 weeks of withdrawal) to confirm that long-term PPI therapy is needed.

A recent American Gastroenterological Association Clinical Practice Update for evaluation and management of gastroesophageal reflux disease (GERD) focuses on delivering personalized diagnostic and therapeutic strategies.

The document includes new advice on use of upfront objective testing for isolated extraesophageal symptoms, confirmation of GERD diagnosis prior to long-term GERD therapy even in PPI responders, as well as important elements focused on personalization of therapy.

Tharakorn/Getty Images

Although GERD is common, with an estimated 30% of people in the United States experiencing symptoms, up to half of all individuals on proton pump inhibitor (PPI) therapy report incomplete symptom improvement. That could be due to the heterogeneous nature of symptoms, which may include heartburn and regurgitation, chest pain, and cough or sore throat, among others. Other conditions may produce similar symptoms or could be exacerbated by the presence of GERD.

The authors of the expert review, published in Clinical Gastroenterology and Hepatology, note that these considerations have driven increased interest in personalized approaches to the management of GERD. The practice update includes sections on how to approach GERD symptoms in the clinic, personalized diagnosis related to GERD symptoms, and precision management.

In the initial management, the authors offer advice on involving the patient in creating a care plan, patient education, and conducting a 4- to 8-week PPI trial in patients with heartburn, regurgitation, or noncardiac chest pains without accompanying alarm signals. If symptoms don’t improve to the patient’s satisfaction, dosing can be boosted to twice per day, or a more effective acid suppressor can be substituted and continued at a once-daily dose. When the response to PPIs is adequate, the dose should be reduced until the lowest effective dose is reached, or the patient could potentially be moved to H2 receptor antagonists or other antacids. However, patients with erosive esophagitis, biopsy-confirmed Barrett’s esophagus, or peptic stricture must stay on long-term PPI therapy.

The authors also gave advice on when to conduct objective testing. When a PPI trial doesn’t adequately address troublesome heartburn, regurgitation, and/or noncardiac chest pain, or if alarm systems are present, endoscopy should be employed to look for erosive reflux disease or long-segment Barrett’s esophagus as conclusive evidence for GERD. If these are absent, prolonged wireless pH monitoring while a patient is off medication is suggested. In addition, patients with extraesophageal symptoms suspected to be caused by reflux should undergo upfront objective reflux testing while off PPI therapy rather than doing an empiric PPI trial.

The authors advise that, if patients don’t have proven GERD and are continued on PPI therapy, they should be evaluated within 12 months to ensure that the therapy and dose are appropriate. Physicians should offer endoscopy with prolonged wireless reflux monitoring in the absence of PPI therapy (ideally after 2-4 weeks of withdrawal) to confirm that long-term PPI therapy is needed.

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

An American Gastroenterological Association practice update on deprescribing proton-pump inhibitors (PPIs) delineates conditions under which drug withdrawal should be considered, and acknowledges that conversations between physicians and patients can be complicated. An inappropriate decision to discontinue PPI therapy can have significant consequences for the patient, while continued inappropriate use raises health care costs and may rarely lead to adverse effects.

One purpose of the update is to provide guidance when patients and providers don’t have the resources to systematically examine the issue, especially when other medical concerns may be in play. The authors also suggested that physicians include pharmacists in the employment of the best practices advice.

monkeybusinessimages/Thinkstock

“None of these statements represents a radical departure from previously published guidance on PPI appropriateness and deprescribing: Our [recommendations] simply seek to summarize the evidence and to provide the clinician with a single document which distills the evidence down into clinically applicable guidance statements,” Laura Targownik, MD, associate professor of medicine at the University of Toronto and corresponding author of the practice update published in Gastroenterology said in an interview.

“PPIs are highly effective medications for specific gastrointestinal conditions, and are largely safe. However, PPIs are often used in situations where they have minimal and no proven benefit, leading to unnecessary health care spending and unnecessary exposure to drugs. Our paper helps clinicians identify which patients require long-term PPI use as well as those who may be using them unnecessarily, and provides actionable advice on how to deprescribe PPIs from those deemed to be using them without clear benefit,” said Dr. Targownik.

An estimated 7%-15% of health care patients in general and 40% of those over 70 use PPIs at any given time, making them among the most commonly used drugs. About one in four patients who start PPIs will use them for a year or more. Aside from their use for acid-mediated upper gastrointestinal conditions, PPIs often find use for less well-defined complaints. Since PPIs are available over the counter, physicians may not even be involved in a patient’s decision to use them.

Although PPI use has been associated with adverse events, including chronic kidney disease, fractures, dementia, and greater risk of COVID-19 infection, there is not high-quality evidence to suggest that PPIs are directly responsible for any of these adverse events.

The authors suggested the primary care provider should periodically review and document the complaints or indications that prompt PPI use. When a patient is found to have no chronic condition that PPIs could reasonably address, the physician should consider a trial withdrawal. Patients who take PPIs twice daily for a known chronic condition should be considered for a reduction to a once-daily dose.

In general, PPI discontinuation is not a good option for most patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture. The same is true for patients with Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis.

Before any deprescribing is considered, the patient should be evaluated for risk of upper gastrointestinal bleeding, and those at high risk are not candidates for PPI deprescribing.

When the decision is made to withdraw PPIs, the patient should be advised of an increased risk of transient upper gastrointestinal symptoms caused by rebound acid hypersecretion.

The withdrawal of PPIs can be done abruptly, or the dose can be tapered gradually.

PPI-associated adverse events should not be a consideration when discussing the option of withdrawing from PPIs. Instead, the decision should be based on the absence of a specific reason for their use. A history of such adverse events, or a current adverse event, should not be a sole reason for discontinuation, nor should risk factors associated with risk of adverse events. Concerns about adverse events have driven recent interest in reducing use of PPIs, but those adverse events were identified through retrospective studies and may be only associated with PPI use rather than caused by it. In many cases there is no plausible mechanistic cause, and no clinical trials have demonstrated increased adverse events in PPI users.

Three-quarters of physicians say they have altered treatment plans for patients because of concerns about PPI adverse events, and 80% say they would advise patients to withdraw PPIs if they learned the patient was at increased risk of upper gastrointestinal bleeding. Unnecessary withdrawal can lead to recurrent symptoms and complications when PPIs are effective treatments. “Therefore, physicians should not use concern about unproven complications of PPI use as a justification for PPI deprescribing if there remain ongoing valid indications for PPI use,” the authors wrote.

Dr. Targownik has received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Janssen Canada, Roche Canada, and Sandoz Canada. She is the lead on an IBD registry supported by AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, Amgen Canada, Roche Canada, and Sandoz Canada. None of the companies with whom Dr. Targownik has a relation are involved in the manufacturing, distribution, or sales of PPIs or any other agents mentioned in the manuscript.

The next generation of COVID-19 vaccines should be able to fight off a new strain and be given each year, a panel of experts that advises the Food and Drug Administration said April 6.

But members of the panel also acknowledged that it will be an uphill battle to reach that goal, especially given how quickly the virus continues to change.

The members of the Vaccines and Related Biological Products Advisory Committee said they want to find the balance that makes sure Americans are protected against severe illness and death but doesn’t wear them out with constant recommendations for boosters.

“We don’t feel comfortable with multiple boosters every 8 weeks,” said committee chairman Arnold Monto, MD, professor emeritus of public health at the University of Michigan, Ann Arbor. “We’d love to see an annual vaccination similar to influenza but realize that the evolution of the virus will dictate how we respond in terms of additional vaccine doses.”

The virus itself will dictate vaccination plans, he said.

The government must also keep its focus on convincing Americans who haven’t been vaccinated to join the club, said committee member Henry H. Bernstein, DO, given that “it seems quite obvious that those who are vaccinated do better than those who aren’t vaccinated.”

The government should clearly communicate to the public the goals of vaccination, he said.

“I would suggest that our overall aim is to prevent severe disease, hospitalization, and death more than just infection prevention,” said Dr. Bernstein, professor of pediatrics at Hofstra University, Hempstead, N.Y.

The FDA called the meeting of its advisers to discuss overall booster and vaccine strategy, even though it already authorized a fourth dose of the Pfizer and Moderna vaccines for certain immune compromised adults and for everyone over age 50.

Early in the all-day meeting, temporary committee member James Hildreth, MD, the president of Meharry Medical College, Nashville, Tenn., asked why that authorization was given without the panel’s input. Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the decision was based on data from the United Kingdom and Israel that suggested immunity from a third shot was already waning.

Dr. Marks later said the fourth dose was “authorized as a stopgap measure until we could get something else in place,” because the aim was to protect older Americans who had died at a higher rate than younger individuals.

“I think we’re very much on board that we simply can’t be boosting people as frequently as we are,” said Dr. Marks.
 

Not enough information to make broader plan

The meeting was meant to be a larger conversation about how to keep pace with the evolving virus and to set up a vaccine selection and development process to better and more quickly respond to changes, such as new variants.

But committee members said they felt stymied by a lack of information. They wanted more data from vaccine manufacturers’ clinical trials. And they noted that so far, there’s no objective, reliable lab-based measurement of COVID-19 vaccine effectiveness – known as a correlate of immunity. Instead, public health officials have looked at rates of hospitalizations and deaths to measure whether the vaccine is still offering protection.

“The question is, what is insufficient protection?” asked H. Cody Meissner, MD, director of pediatric infectious disease at Tufts Medical Center in Boston. “At what point will we say the vaccine isn’t working well enough?”

Centers for Disease Control and Prevention officials presented data showing that a third shot has been more effective than a two-shot regimen in preventing serious disease and death, and that the three shots were significantly more protective than being unvaccinated.

In February, as the Omicron variant continued to rage, unvaccinated Americans aged 5 years and older had an almost three times higher risk of testing positive, and nine times higher risk of dying, compared with those who were considered fully vaccinated, said Heather Scobie, PhD, MPH, a member of the CDC’s COVID-19 Emergency Response team.

But only 98 million Americans – about half of those aged 12 years or older – have received a third dose, Dr. Scobie said.

It’s also still not clear how much more protection a fourth shot adds, or how long it will last. The committee heard data on a just-published study of a fourth dose of the Pfizer vaccine given to some 600,000 Israelis during the Omicron wave from January to March. The rate of severe COVID-19 was 3.5 times lower in the group that received a fourth dose, compared with those who had gotten only three shots, and protection lasted for at least 12 weeks.

Still, study authors said, any protection against infection itself was “short lived.”


 

More like flu vaccine?

The advisers discussed the possibility of making COVID-19 vaccine development similar to the process for the flu vaccine but acknowledged many difficulties.

The flu predictably hits during the winter in each hemisphere and a global surveillance network helps the World Health Organization decide on the vaccine strains each year. Then each nation’s regulatory and public health officials choose the strains for their shot and vaccine makers begin what is typically a 6-month-long manufacturing process.

COVID outbreaks have happened during all seasons and new variants haven’t always hit every country in a similar fashion. The COVID virus has mutated at five times the speed of the flu virus – producing a new dominant strain in a year, compared with the 3-5 years it takes for the flu virus to do so, said Trevor Bedford, PhD, a professor in the vaccine and infectious disease division at the Fred Hutchinson Cancer Research Center in Seattle.

Global COVID surveillance is patchy and the WHO has not yet created a program to help select strains for a COVID-19 vaccine but is working on a process. Currently, vaccine makers seem to be driving vaccine strain selection, said panelist Paul Offit, MD, professor of paediatrics at Children’s Hospital of Philadelphia. “I feel like to some extent the companies dictate the conversation. It shouldn’t come from them. It should come from us.”

“The important thing is that the public understands how complex this is,” said temporary committee member Oveta A. Fuller, PhD, associate professor of microbiology and immunology at the University of Michigan. “We didn’t get to understand influenza in 2 years. It’s taken years to get an imperfect but useful process to deal with flu.”

A version of this article first appeared on WebMD.com.

The next generation of COVID-19 vaccines should be able to fight off a new strain and be given each year, a panel of experts that advises the Food and Drug Administration said April 6.

But members of the panel also acknowledged that it will be an uphill battle to reach that goal, especially given how quickly the virus continues to change.

The members of the Vaccines and Related Biological Products Advisory Committee said they want to find the balance that makes sure Americans are protected against severe illness and death but doesn’t wear them out with constant recommendations for boosters.

“We don’t feel comfortable with multiple boosters every 8 weeks,” said committee chairman Arnold Monto, MD, professor emeritus of public health at the University of Michigan, Ann Arbor. “We’d love to see an annual vaccination similar to influenza but realize that the evolution of the virus will dictate how we respond in terms of additional vaccine doses.”

The virus itself will dictate vaccination plans, he said.

The government must also keep its focus on convincing Americans who haven’t been vaccinated to join the club, said committee member Henry H. Bernstein, DO, given that “it seems quite obvious that those who are vaccinated do better than those who aren’t vaccinated.”

The government should clearly communicate to the public the goals of vaccination, he said.

“I would suggest that our overall aim is to prevent severe disease, hospitalization, and death more than just infection prevention,” said Dr. Bernstein, professor of pediatrics at Hofstra University, Hempstead, N.Y.

The FDA called the meeting of its advisers to discuss overall booster and vaccine strategy, even though it already authorized a fourth dose of the Pfizer and Moderna vaccines for certain immune compromised adults and for everyone over age 50.

Early in the all-day meeting, temporary committee member James Hildreth, MD, the president of Meharry Medical College, Nashville, Tenn., asked why that authorization was given without the panel’s input. Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the decision was based on data from the United Kingdom and Israel that suggested immunity from a third shot was already waning.

Dr. Marks later said the fourth dose was “authorized as a stopgap measure until we could get something else in place,” because the aim was to protect older Americans who had died at a higher rate than younger individuals.

“I think we’re very much on board that we simply can’t be boosting people as frequently as we are,” said Dr. Marks.
 

Not enough information to make broader plan

The meeting was meant to be a larger conversation about how to keep pace with the evolving virus and to set up a vaccine selection and development process to better and more quickly respond to changes, such as new variants.

But committee members said they felt stymied by a lack of information. They wanted more data from vaccine manufacturers’ clinical trials. And they noted that so far, there’s no objective, reliable lab-based measurement of COVID-19 vaccine effectiveness – known as a correlate of immunity. Instead, public health officials have looked at rates of hospitalizations and deaths to measure whether the vaccine is still offering protection.

“The question is, what is insufficient protection?” asked H. Cody Meissner, MD, director of pediatric infectious disease at Tufts Medical Center in Boston. “At what point will we say the vaccine isn’t working well enough?”

Centers for Disease Control and Prevention officials presented data showing that a third shot has been more effective than a two-shot regimen in preventing serious disease and death, and that the three shots were significantly more protective than being unvaccinated.

In February, as the Omicron variant continued to rage, unvaccinated Americans aged 5 years and older had an almost three times higher risk of testing positive, and nine times higher risk of dying, compared with those who were considered fully vaccinated, said Heather Scobie, PhD, MPH, a member of the CDC’s COVID-19 Emergency Response team.

But only 98 million Americans – about half of those aged 12 years or older – have received a third dose, Dr. Scobie said.

It’s also still not clear how much more protection a fourth shot adds, or how long it will last. The committee heard data on a just-published study of a fourth dose of the Pfizer vaccine given to some 600,000 Israelis during the Omicron wave from January to March. The rate of severe COVID-19 was 3.5 times lower in the group that received a fourth dose, compared with those who had gotten only three shots, and protection lasted for at least 12 weeks.

Still, study authors said, any protection against infection itself was “short lived.”


 

More like flu vaccine?

The advisers discussed the possibility of making COVID-19 vaccine development similar to the process for the flu vaccine but acknowledged many difficulties.

The flu predictably hits during the winter in each hemisphere and a global surveillance network helps the World Health Organization decide on the vaccine strains each year. Then each nation’s regulatory and public health officials choose the strains for their shot and vaccine makers begin what is typically a 6-month-long manufacturing process.

COVID outbreaks have happened during all seasons and new variants haven’t always hit every country in a similar fashion. The COVID virus has mutated at five times the speed of the flu virus – producing a new dominant strain in a year, compared with the 3-5 years it takes for the flu virus to do so, said Trevor Bedford, PhD, a professor in the vaccine and infectious disease division at the Fred Hutchinson Cancer Research Center in Seattle.

Global COVID surveillance is patchy and the WHO has not yet created a program to help select strains for a COVID-19 vaccine but is working on a process. Currently, vaccine makers seem to be driving vaccine strain selection, said panelist Paul Offit, MD, professor of paediatrics at Children’s Hospital of Philadelphia. “I feel like to some extent the companies dictate the conversation. It shouldn’t come from them. It should come from us.”

“The important thing is that the public understands how complex this is,” said temporary committee member Oveta A. Fuller, PhD, associate professor of microbiology and immunology at the University of Michigan. “We didn’t get to understand influenza in 2 years. It’s taken years to get an imperfect but useful process to deal with flu.”

A version of this article first appeared on WebMD.com.

The next generation of COVID-19 vaccines should be able to fight off a new strain and be given each year, a panel of experts that advises the Food and Drug Administration said April 6.

But members of the panel also acknowledged that it will be an uphill battle to reach that goal, especially given how quickly the virus continues to change.

The members of the Vaccines and Related Biological Products Advisory Committee said they want to find the balance that makes sure Americans are protected against severe illness and death but doesn’t wear them out with constant recommendations for boosters.

“We don’t feel comfortable with multiple boosters every 8 weeks,” said committee chairman Arnold Monto, MD, professor emeritus of public health at the University of Michigan, Ann Arbor. “We’d love to see an annual vaccination similar to influenza but realize that the evolution of the virus will dictate how we respond in terms of additional vaccine doses.”

The virus itself will dictate vaccination plans, he said.

The government must also keep its focus on convincing Americans who haven’t been vaccinated to join the club, said committee member Henry H. Bernstein, DO, given that “it seems quite obvious that those who are vaccinated do better than those who aren’t vaccinated.”

The government should clearly communicate to the public the goals of vaccination, he said.

“I would suggest that our overall aim is to prevent severe disease, hospitalization, and death more than just infection prevention,” said Dr. Bernstein, professor of pediatrics at Hofstra University, Hempstead, N.Y.

The FDA called the meeting of its advisers to discuss overall booster and vaccine strategy, even though it already authorized a fourth dose of the Pfizer and Moderna vaccines for certain immune compromised adults and for everyone over age 50.

Early in the all-day meeting, temporary committee member James Hildreth, MD, the president of Meharry Medical College, Nashville, Tenn., asked why that authorization was given without the panel’s input. Peter Marks, MD, the director of FDA’s Center for Biologics Evaluation and Research, said the decision was based on data from the United Kingdom and Israel that suggested immunity from a third shot was already waning.

Dr. Marks later said the fourth dose was “authorized as a stopgap measure until we could get something else in place,” because the aim was to protect older Americans who had died at a higher rate than younger individuals.

“I think we’re very much on board that we simply can’t be boosting people as frequently as we are,” said Dr. Marks.
 

Not enough information to make broader plan

The meeting was meant to be a larger conversation about how to keep pace with the evolving virus and to set up a vaccine selection and development process to better and more quickly respond to changes, such as new variants.

But committee members said they felt stymied by a lack of information. They wanted more data from vaccine manufacturers’ clinical trials. And they noted that so far, there’s no objective, reliable lab-based measurement of COVID-19 vaccine effectiveness – known as a correlate of immunity. Instead, public health officials have looked at rates of hospitalizations and deaths to measure whether the vaccine is still offering protection.

“The question is, what is insufficient protection?” asked H. Cody Meissner, MD, director of pediatric infectious disease at Tufts Medical Center in Boston. “At what point will we say the vaccine isn’t working well enough?”

Centers for Disease Control and Prevention officials presented data showing that a third shot has been more effective than a two-shot regimen in preventing serious disease and death, and that the three shots were significantly more protective than being unvaccinated.

In February, as the Omicron variant continued to rage, unvaccinated Americans aged 5 years and older had an almost three times higher risk of testing positive, and nine times higher risk of dying, compared with those who were considered fully vaccinated, said Heather Scobie, PhD, MPH, a member of the CDC’s COVID-19 Emergency Response team.

But only 98 million Americans – about half of those aged 12 years or older – have received a third dose, Dr. Scobie said.

It’s also still not clear how much more protection a fourth shot adds, or how long it will last. The committee heard data on a just-published study of a fourth dose of the Pfizer vaccine given to some 600,000 Israelis during the Omicron wave from January to March. The rate of severe COVID-19 was 3.5 times lower in the group that received a fourth dose, compared with those who had gotten only three shots, and protection lasted for at least 12 weeks.

Still, study authors said, any protection against infection itself was “short lived.”


 

More like flu vaccine?

The advisers discussed the possibility of making COVID-19 vaccine development similar to the process for the flu vaccine but acknowledged many difficulties.

The flu predictably hits during the winter in each hemisphere and a global surveillance network helps the World Health Organization decide on the vaccine strains each year. Then each nation’s regulatory and public health officials choose the strains for their shot and vaccine makers begin what is typically a 6-month-long manufacturing process.

COVID outbreaks have happened during all seasons and new variants haven’t always hit every country in a similar fashion. The COVID virus has mutated at five times the speed of the flu virus – producing a new dominant strain in a year, compared with the 3-5 years it takes for the flu virus to do so, said Trevor Bedford, PhD, a professor in the vaccine and infectious disease division at the Fred Hutchinson Cancer Research Center in Seattle.

Global COVID surveillance is patchy and the WHO has not yet created a program to help select strains for a COVID-19 vaccine but is working on a process. Currently, vaccine makers seem to be driving vaccine strain selection, said panelist Paul Offit, MD, professor of paediatrics at Children’s Hospital of Philadelphia. “I feel like to some extent the companies dictate the conversation. It shouldn’t come from them. It should come from us.”

“The important thing is that the public understands how complex this is,” said temporary committee member Oveta A. Fuller, PhD, associate professor of microbiology and immunology at the University of Michigan. “We didn’t get to understand influenza in 2 years. It’s taken years to get an imperfect but useful process to deal with flu.”

A version of this article first appeared on WebMD.com.

Federal regulators have announced that GlaxoSmithKline’s COVID-19 drug should no longer be used because it’s likely ineffective against BA.2, the Omicron subvariant that now accounts for most new cases in the United States, The Associated Press reports.

The Food and Drug Administration announced that the antibody drug sotrovimab is no longer authorized to treat patients in U.S. states or territories. The decision was expected, as the FDA restricted the drug’s use across the country throughout March as BA.2 became dominant in certain regions, the AP reported.

The BA.2 subvariant now accounts for 72% of new COVID-19 cases sequenced by health authorities, according to the latest CDC data updated April 5. The FDA cited the CDC data in its reason for pulling back on the authorization of the drug.

The GlaxoSmithKline drug is the latest antibody medication to be pulled due to coronavirus mutations. In January, the FDA halted the use of antibody drugs from Regeneron and Eli Lilly because they didn’t work against the Omicron variant.

The FDA’s decision means that one antibody drug is still authorized for use against routine COVID-19 cases, the AP reported. A different Eli Lilly drug – bebtelovimab – still appears to work against BA.2.

Doctors can also prescribe antiviral pills, which typically affect the coronavirus spike protein and aren’t affected by mutations, to treat mild to moderate COVID-19, the AP reported. The authorized pills from Pfizer and Merck – Paxlovid and Lagevrio – have been shipped to pharmacy chains and medical clinics in hopes of getting them to patients early enough to work.

The federal government purchased nearly $2 billion worth of the GlaxoSmithKline drug and shipped more than 900,000 doses to states last fall, the AP reported. In March, the company announced that it was studying a higher dose that could be effective against BA.2, which would require FDA approval before resuming use in the United States.

The antibody drugs mimic the virus-blocking proteins found in the human body, the AP reported. They’re designed to attack a specific virus and need to be updated as the coronavirus mutates.

A version of this article first appeared on WebMD.com.

Federal regulators have announced that GlaxoSmithKline’s COVID-19 drug should no longer be used because it’s likely ineffective against BA.2, the Omicron subvariant that now accounts for most new cases in the United States, The Associated Press reports.

The Food and Drug Administration announced that the antibody drug sotrovimab is no longer authorized to treat patients in U.S. states or territories. The decision was expected, as the FDA restricted the drug’s use across the country throughout March as BA.2 became dominant in certain regions, the AP reported.

The BA.2 subvariant now accounts for 72% of new COVID-19 cases sequenced by health authorities, according to the latest CDC data updated April 5. The FDA cited the CDC data in its reason for pulling back on the authorization of the drug.

The GlaxoSmithKline drug is the latest antibody medication to be pulled due to coronavirus mutations. In January, the FDA halted the use of antibody drugs from Regeneron and Eli Lilly because they didn’t work against the Omicron variant.

The FDA’s decision means that one antibody drug is still authorized for use against routine COVID-19 cases, the AP reported. A different Eli Lilly drug – bebtelovimab – still appears to work against BA.2.

Doctors can also prescribe antiviral pills, which typically affect the coronavirus spike protein and aren’t affected by mutations, to treat mild to moderate COVID-19, the AP reported. The authorized pills from Pfizer and Merck – Paxlovid and Lagevrio – have been shipped to pharmacy chains and medical clinics in hopes of getting them to patients early enough to work.

The federal government purchased nearly $2 billion worth of the GlaxoSmithKline drug and shipped more than 900,000 doses to states last fall, the AP reported. In March, the company announced that it was studying a higher dose that could be effective against BA.2, which would require FDA approval before resuming use in the United States.

The antibody drugs mimic the virus-blocking proteins found in the human body, the AP reported. They’re designed to attack a specific virus and need to be updated as the coronavirus mutates.

A version of this article first appeared on WebMD.com.

Federal regulators have announced that GlaxoSmithKline’s COVID-19 drug should no longer be used because it’s likely ineffective against BA.2, the Omicron subvariant that now accounts for most new cases in the United States, The Associated Press reports.

The Food and Drug Administration announced that the antibody drug sotrovimab is no longer authorized to treat patients in U.S. states or territories. The decision was expected, as the FDA restricted the drug’s use across the country throughout March as BA.2 became dominant in certain regions, the AP reported.

The BA.2 subvariant now accounts for 72% of new COVID-19 cases sequenced by health authorities, according to the latest CDC data updated April 5. The FDA cited the CDC data in its reason for pulling back on the authorization of the drug.

The GlaxoSmithKline drug is the latest antibody medication to be pulled due to coronavirus mutations. In January, the FDA halted the use of antibody drugs from Regeneron and Eli Lilly because they didn’t work against the Omicron variant.

The FDA’s decision means that one antibody drug is still authorized for use against routine COVID-19 cases, the AP reported. A different Eli Lilly drug – bebtelovimab – still appears to work against BA.2.

Doctors can also prescribe antiviral pills, which typically affect the coronavirus spike protein and aren’t affected by mutations, to treat mild to moderate COVID-19, the AP reported. The authorized pills from Pfizer and Merck – Paxlovid and Lagevrio – have been shipped to pharmacy chains and medical clinics in hopes of getting them to patients early enough to work.

The federal government purchased nearly $2 billion worth of the GlaxoSmithKline drug and shipped more than 900,000 doses to states last fall, the AP reported. In March, the company announced that it was studying a higher dose that could be effective against BA.2, which would require FDA approval before resuming use in the United States.

The antibody drugs mimic the virus-blocking proteins found in the human body, the AP reported. They’re designed to attack a specific virus and need to be updated as the coronavirus mutates.

A version of this article first appeared on WebMD.com.

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.

Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.

The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.

The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.

That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.

Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”

Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.

So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.

To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.

If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.

Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.

“It’s always a good question for health care,” she said, “are we doing more than we need to?”

Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.

“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”

The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.

“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”

The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.

“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.

The study authors and Dr. Zapata reported no relevant financial relationships.

Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.

Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.

The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.

The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.

That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.

Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”

Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.

So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.

To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.

If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.

Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.

“It’s always a good question for health care,” she said, “are we doing more than we need to?”

Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.

“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”

The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.

“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”

The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.

“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.

The study authors and Dr. Zapata reported no relevant financial relationships.

Premature births from cesarean (C-section) and induced deliveries dropped abruptly by 6.5% from the projected number in the first month of the COVID-19 pandemic and stayed at the lower rate consistently throughout the year, researchers have found.

Results of the study, led by Daniel Dench, PhD, assistant professor at the Georgia Institute of Technology School of Economics in Atlanta, were published online in Pediatrics.

The authors say their findings help answer the question of whether numbers of preterm (less than 37 weeks gestation) C-sections and induced deliveries would change if women didn’t see their physicians during pregnancy as often, especially in person, and raise the question of whether some birth interventions by physicians may not be necessary. The pandemic gave researchers a natural, ethical way to study the question.

The researchers found that in March 2020 – the start of business closures and stay-at-home orders around the country – preterm births from C-sections or induced deliveries immediately fell from the forecast number for the month by 0.4 percentage points. For the rest of 2020, the number remained on average 0.35 percentage points below the numbers predicted.

That means 350 fewer preterm C-sections and induced deliveries per 100,000 live births, or 10,000 fewer overall, the authors said.

Dr. Dench told this publication the numbers for those births had been steady from January 2010 to February 2020, but the pattern “diverges from this trend very clearly beginning exactly in March 2020 and does not return to trend by December 2020.”

Meanwhile, during the study period, the number of full-term cesarean and induced deliveries stayed steady and started to increase slightly in 2020. Researchers also adjusted for seasonality as, for example, preterm births are higher on average in February than in March.

So far, Dr. Dench said in a press release, it’s not clear whether the lower numbers mean physicians didn’t deliver babies that ended up surviving in the womb anyway or if they missed some that would die in the womb without intervention.

To better understand those implications, Dr. Dench says he is turning to fetal death records for March-December 2020 and he said he expects to have those results analyzed by the end of the year.

If there was no change in fetal deaths at the same time as the drop in preterm births, Dr. Dench said, that could point to physician interventions that may not have been necessary.

Mya R. Zapata, MD, an obstetrician-gynecologist with UCLA Health, who was not involved with the study, told this publication that checking the fetal deaths is a good start and an objective outcome in answering the question, but she points out there are other outcomes that will take a deeper analysis, such as whether there are differences later in developmental outcomes after fewer physician visits.

“It’s always a good question for health care,” she said, “are we doing more than we need to?”

Dr. Zapata is the obstetrics service chief for UCLA’s labor and delivery unit and was an integral part of decision-making as to what services were essential and for which patients. She said the fewer visits and fewer ultrasounds the researchers describe fit with what ob.gyns. at UCLA experienced as the pandemic hit.

“We really tried to hone in on people who were at highest risk for an adverse outcome,” she said. “I still have the question of whether there were things we missed in low-risk people. It will take time to get the entire answer. But it does make us reflect that perhaps less intervention could be better for patients and easier. It’s our job in medicine to keep asking the question of what is essential and safe and not just continue with current practice because that’s what we’ve always done.”

The amount of data gave the researchers an unusual view. They studied 38,891,271 singleton births in the United States from 2010 to 2020 with data from the National Center for Health Statistics.

“If you look at 1,000 births in a single hospital, or even at 30,000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” Dr. Dench said. “The drop we detected is a huge change, but you might miss it in a small sample.”

The researchers acknowledge a limitation of the study is that half of all preterm C-sections and induced deliveries happen because of a ruptured membrane, a spontaneous cause. Those instances can’t be distinguished from the ones caused by doctors’ interventions in this study.

“Still, these findings are significant because the causes for preterm births are not always known,” the authors wrote in the press release.

The study authors and Dr. Zapata reported no relevant financial relationships.

Patients who leave a hospital against medical advice may be called “difficult” or “uncooperative.” But a new study suggests that in many cases, that label is unfair.

The analysis found that in about 1 in 5 cases, shortcomings in the quality of care and other factors beyond patients’ control explain why they leave the hospital before completing recommended treatment.

Clinicians may be quick to blame patients for so-called discharges against medical advice (AMA), which comprise up to 2% of hospital admissions and are associated with an increased risk of mortality and readmission. But “we as providers are very much involved in the reasons why these patients left,” Kushinga Bvute, MD, MPH, a second-year internal medicine resident at Florida Atlantic University, Boca Raton, who led the new study, told this news organization. Dr. Bvute and her colleagues presented their findings April 6 at the Society of General Internal Medicine (SGIM) 2022 Annual Meeting, Orlando, Florida.

Dr. Bvute and her colleagues reviewed the records of 548 AMA discharges – out of a total of 354,767 discharges – from Boca Raton Regional Hospital from January 2020 to January 2021. In 44% of cases, patients cited their own reasons for leaving. But in nearly 20% of AMA discharges, the researchers identified factors linked to treatment.

Hospital-related reasons patients cited for leaving AMA were general wait times (3.5%), provider wait times (2.6%), provider care (2.9%), the hospital environment (2.7%), wanting a private room (2%), and seeking medical care elsewhere (6.2%).

Patient-related factors were refusing treatment (27%), feeling better (3.5%), addiction problems (2.9%), financial complications (2.9%), and dependent care (2.4%). Ten (1.8%) eloped, according to the researchers.

Nearly 60% of patients who were discharged AMA were men, with a mean age of 56 years (standard deviation, 19.13). The average stay was 1.64 days.

In roughly one-third of cases, there was no documented reason for the departure – underscoring the need for better reporting, according to the researchers.

To address AMA discharges, hospitals “need to focus on factors they influence, such as high-quality patient care, the hospital environment, and provider-patient relationships,” the researchers report.
 

New procedures needed

The hospital is working on procedures to ensure that reasons for AMA discharges are documented. The administration also is implementing preventive steps, such as communicating with patients about the risks of leaving and providing discharge plans to reduce the likelihood that a patient will return, Dr. Bvute told this news organization.

Dr. Bvute said the findings should encourage individual clinicians to “remove any stereotypes that sometimes come attached to having those three letters on your charts.”

Data were collected during the COVID-19 pandemic, but Dr. Bvute does not believe that fear of coronavirus exposure drove many patients to leave the hospital prematurely.

The study is notable for approaching AMA discharges from a quality improvement perspective, David Alfandre, MD, MPH, a health care ethicist at the VA National Center for Ethics in Health Care, Washington, D.C., said in an interview.

Dr. Alfandre, who was not involved in the study, said it reflects growing recognition that hospitals can take steps to reduce adverse outcomes associated with AMA discharges. “It’s starting to shift the conversation to saying, this isn’t just the patient’s problem, but this is the health care provider’s problem,” he said.

Dr. Alfandre co-authored a 2021 analysis showing that hospital characteristics account for 7.3% of variation in the probability of a patient being discharged AMA. However, research is needed to identify effective interventions besides the established use of buprenorphine and naloxone for patients with opioid use disorder. “I think everybody recognizes the quality of communication is poor, but that doesn’t really help us operationalize that to know what to do,” he said.

Emily Holmes, MD, MPH, medical director of the Changing Health Outcomes Through Integrated Care Excellence Program at IU Health, Indianapolis, cautioned that data may be biased because defining AMA discharge can be subjective.

Reasons are not consistently documented and can be difficult to capture because they are often multifactorial, Dr. Holmes said. “For example, long wait times are more problematic when a patient is worried about finances and care for a child,” she said.

But Dr. Holmes, who was not involved in the study, said it does encourage clinicians “to think about what we can do systematically to reduce AMA discharges.”

Dr. Bvute, Dr. Alfandre, and Dr. Holmes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who leave a hospital against medical advice may be called “difficult” or “uncooperative.” But a new study suggests that in many cases, that label is unfair.

The analysis found that in about 1 in 5 cases, shortcomings in the quality of care and other factors beyond patients’ control explain why they leave the hospital before completing recommended treatment.

Clinicians may be quick to blame patients for so-called discharges against medical advice (AMA), which comprise up to 2% of hospital admissions and are associated with an increased risk of mortality and readmission. But “we as providers are very much involved in the reasons why these patients left,” Kushinga Bvute, MD, MPH, a second-year internal medicine resident at Florida Atlantic University, Boca Raton, who led the new study, told this news organization. Dr. Bvute and her colleagues presented their findings April 6 at the Society of General Internal Medicine (SGIM) 2022 Annual Meeting, Orlando, Florida.

Dr. Bvute and her colleagues reviewed the records of 548 AMA discharges – out of a total of 354,767 discharges – from Boca Raton Regional Hospital from January 2020 to January 2021. In 44% of cases, patients cited their own reasons for leaving. But in nearly 20% of AMA discharges, the researchers identified factors linked to treatment.

Hospital-related reasons patients cited for leaving AMA were general wait times (3.5%), provider wait times (2.6%), provider care (2.9%), the hospital environment (2.7%), wanting a private room (2%), and seeking medical care elsewhere (6.2%).

Patient-related factors were refusing treatment (27%), feeling better (3.5%), addiction problems (2.9%), financial complications (2.9%), and dependent care (2.4%). Ten (1.8%) eloped, according to the researchers.

Nearly 60% of patients who were discharged AMA were men, with a mean age of 56 years (standard deviation, 19.13). The average stay was 1.64 days.

In roughly one-third of cases, there was no documented reason for the departure – underscoring the need for better reporting, according to the researchers.

To address AMA discharges, hospitals “need to focus on factors they influence, such as high-quality patient care, the hospital environment, and provider-patient relationships,” the researchers report.
 

New procedures needed

The hospital is working on procedures to ensure that reasons for AMA discharges are documented. The administration also is implementing preventive steps, such as communicating with patients about the risks of leaving and providing discharge plans to reduce the likelihood that a patient will return, Dr. Bvute told this news organization.

Dr. Bvute said the findings should encourage individual clinicians to “remove any stereotypes that sometimes come attached to having those three letters on your charts.”

Data were collected during the COVID-19 pandemic, but Dr. Bvute does not believe that fear of coronavirus exposure drove many patients to leave the hospital prematurely.

The study is notable for approaching AMA discharges from a quality improvement perspective, David Alfandre, MD, MPH, a health care ethicist at the VA National Center for Ethics in Health Care, Washington, D.C., said in an interview.

Dr. Alfandre, who was not involved in the study, said it reflects growing recognition that hospitals can take steps to reduce adverse outcomes associated with AMA discharges. “It’s starting to shift the conversation to saying, this isn’t just the patient’s problem, but this is the health care provider’s problem,” he said.

Dr. Alfandre co-authored a 2021 analysis showing that hospital characteristics account for 7.3% of variation in the probability of a patient being discharged AMA. However, research is needed to identify effective interventions besides the established use of buprenorphine and naloxone for patients with opioid use disorder. “I think everybody recognizes the quality of communication is poor, but that doesn’t really help us operationalize that to know what to do,” he said.

Emily Holmes, MD, MPH, medical director of the Changing Health Outcomes Through Integrated Care Excellence Program at IU Health, Indianapolis, cautioned that data may be biased because defining AMA discharge can be subjective.

Reasons are not consistently documented and can be difficult to capture because they are often multifactorial, Dr. Holmes said. “For example, long wait times are more problematic when a patient is worried about finances and care for a child,” she said.

But Dr. Holmes, who was not involved in the study, said it does encourage clinicians “to think about what we can do systematically to reduce AMA discharges.”

Dr. Bvute, Dr. Alfandre, and Dr. Holmes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who leave a hospital against medical advice may be called “difficult” or “uncooperative.” But a new study suggests that in many cases, that label is unfair.

The analysis found that in about 1 in 5 cases, shortcomings in the quality of care and other factors beyond patients’ control explain why they leave the hospital before completing recommended treatment.

Clinicians may be quick to blame patients for so-called discharges against medical advice (AMA), which comprise up to 2% of hospital admissions and are associated with an increased risk of mortality and readmission. But “we as providers are very much involved in the reasons why these patients left,” Kushinga Bvute, MD, MPH, a second-year internal medicine resident at Florida Atlantic University, Boca Raton, who led the new study, told this news organization. Dr. Bvute and her colleagues presented their findings April 6 at the Society of General Internal Medicine (SGIM) 2022 Annual Meeting, Orlando, Florida.

Dr. Bvute and her colleagues reviewed the records of 548 AMA discharges – out of a total of 354,767 discharges – from Boca Raton Regional Hospital from January 2020 to January 2021. In 44% of cases, patients cited their own reasons for leaving. But in nearly 20% of AMA discharges, the researchers identified factors linked to treatment.

Hospital-related reasons patients cited for leaving AMA were general wait times (3.5%), provider wait times (2.6%), provider care (2.9%), the hospital environment (2.7%), wanting a private room (2%), and seeking medical care elsewhere (6.2%).

Patient-related factors were refusing treatment (27%), feeling better (3.5%), addiction problems (2.9%), financial complications (2.9%), and dependent care (2.4%). Ten (1.8%) eloped, according to the researchers.

Nearly 60% of patients who were discharged AMA were men, with a mean age of 56 years (standard deviation, 19.13). The average stay was 1.64 days.

In roughly one-third of cases, there was no documented reason for the departure – underscoring the need for better reporting, according to the researchers.

To address AMA discharges, hospitals “need to focus on factors they influence, such as high-quality patient care, the hospital environment, and provider-patient relationships,” the researchers report.
 

New procedures needed

The hospital is working on procedures to ensure that reasons for AMA discharges are documented. The administration also is implementing preventive steps, such as communicating with patients about the risks of leaving and providing discharge plans to reduce the likelihood that a patient will return, Dr. Bvute told this news organization.

Dr. Bvute said the findings should encourage individual clinicians to “remove any stereotypes that sometimes come attached to having those three letters on your charts.”

Data were collected during the COVID-19 pandemic, but Dr. Bvute does not believe that fear of coronavirus exposure drove many patients to leave the hospital prematurely.

The study is notable for approaching AMA discharges from a quality improvement perspective, David Alfandre, MD, MPH, a health care ethicist at the VA National Center for Ethics in Health Care, Washington, D.C., said in an interview.

Dr. Alfandre, who was not involved in the study, said it reflects growing recognition that hospitals can take steps to reduce adverse outcomes associated with AMA discharges. “It’s starting to shift the conversation to saying, this isn’t just the patient’s problem, but this is the health care provider’s problem,” he said.

Dr. Alfandre co-authored a 2021 analysis showing that hospital characteristics account for 7.3% of variation in the probability of a patient being discharged AMA. However, research is needed to identify effective interventions besides the established use of buprenorphine and naloxone for patients with opioid use disorder. “I think everybody recognizes the quality of communication is poor, but that doesn’t really help us operationalize that to know what to do,” he said.

Emily Holmes, MD, MPH, medical director of the Changing Health Outcomes Through Integrated Care Excellence Program at IU Health, Indianapolis, cautioned that data may be biased because defining AMA discharge can be subjective.

Reasons are not consistently documented and can be difficult to capture because they are often multifactorial, Dr. Holmes said. “For example, long wait times are more problematic when a patient is worried about finances and care for a child,” she said.

But Dr. Holmes, who was not involved in the study, said it does encourage clinicians “to think about what we can do systematically to reduce AMA discharges.”

Dr. Bvute, Dr. Alfandre, and Dr. Holmes reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

After more than a decade of moving because of medical school, residencies, and international fellowships, Abhi Kole, MD, PhD, is ready to put down roots. But he’s learning that buying a house in today’s housing market is easier said than done.

In the past 6 months, Dr. Kole, an internist at Grady Hospital in Atlanta, put in offers on three houses. None resulted in a purchase. Dr. Kole says he’s learned how to be more competitive with each subsequent offer, starting out with a bid significantly above the asking price and waiving his right to an appraisal or financing contingencies.

The experience has been surprising and disappointing.

“I knew the market was bad when I started looking and that home prices had gone up,” Dr. Kole says. “What I didn’t realize was that it would still be so hard for me. I have a good job, no debt, and great credit.”

Another frustration for Dr. Kole: He’s been approved for a physician’s loan (a type of mortgage that requires a lower down payment and does not count student loans in debt-to-income calculations) from a national bank, but sellers seem to prefer buyers who work with local lenders. Dr. Kole has been willing to waive the appraisal and mortgage contingency on the right home, but he draws the line at waiving the inspection, a trend that some other buyers in his area are going along with.

“With each house, I learn more about how this works and what amount of risk I can safely assume,” Dr. Kobe says. “There are certain things I definitely wouldn’t give up.”

Dr. Kole’s experience mirrors that of millions of other would-be homebuyers navigating a strong seller’s market.

“Potential homebuyers are really facing a triple threat right now,” says Clare Losey, an assistant research economist with the Texas Real Estate Research Center. “There’s high home appreciation, high mortgage rates, and low inventory of homes for sale.”

It’s still possible to find — and buy — your dream home, even in today’s market with all its challenges. Here are some important steps that can help you.
 

1. Do not low ball.

There may be some cases in which you can save money by making an offer significantly below the asking price on a property. However, with most housing areas across the country experiencing a seller’s market, you run the risk of offending the buyer or being dismissed as not having a serious offer.

In today’s market, a better strategy is to go in with close to your best and final offer from the start, realtors say. It can help to waive the appraisal or financing contingency as well, although it’s important to understand the risk associated with doing so. Last month, the average home sold for 103% of the list price, according to data compiled from Statista.
 

2. Get credit ready.

The better your credit, the easier time you’ll have getting a mortgage — and the lower the rate you’ll pay for the loan. The average first-time homebuyer has a credit score of 746, according to a recent paper by Fannie Mae. If you know you’re going to buy a home in the next few months, you can improve your credit by making sure to pay all your bills on time and by avoiding taking on any new debt.

This is also a good opportunity to check your credit report (get all three reports for free from AnnualCreditReport.com) to see whether there are any mistakes or other problems that you’ll need to clear up before applying for a loan. Also, take a look at your credit-utilization ratio (the amount of credit you use compared to the amount available to you). Experts recommend keeping this number below 30%.
 

3. Prepare to move quickly.

Among homes that closed in March, the average number of days on the market (the amount of time between listing and closing) was just 38 days, according to Realtor.com. In busy markets, homes are moving even faster, realtors say, with sellers commonly accepting offers within days of listing their house for sale.

“It’s crazy,” says Sarah Scattini, president of the Reno/Sparks Association of Realtors. “The market is moving extremely fast here. If you list your home, your sale is pending within 5 days.”

In addition to moving quickly to make your initial offer, do the same if a buyer counters with a negotiation. A speedy response will show the buyer that you’re very interested — and to beat out any other bidders who may have also received a counteroffer.
 

4. Shop around for mortgages.

Especially for first-time homebuyers, the process will go much more smoothly if you’ve got a team of professionals to help you. Look for a realtor and a mortgage lender who have experience working with first-time homebuyers and with physicians, if possible.

Since mortgage rates can vary wildly, you’ll want to shop around a bit before settling on a lender. Get quotes from a local lender, an online lender, and, potentially, a credit union or a mortgage broker to get a sense of the types of mortgages and rates available to you.

“With multiple offers on every single listing, you really want to align yourself with a great realtor who can negotiate for you on your behalf and navigate you through this very tricky market,” says Ms. Scattini.

For both your realtor and your lender, you’ll want to know up front how they get paid and how they calculate their fees. Typically, the real estate agents for buyers and sellers split a 6% commission on home sales, meaning that your realtor will likely take home 3% of the purchase price.
 

5. Get preapproved.

Once you’ve settled on a lender, getting preapproved for a mortgage can make your offer more appealing to potential buyers. Preapproval is an in-depth process in which lenders pull your credit and look at other financial factors, such as your income and assets, to tell you ahead of time how much you could borrow under their standards and how much that might cost you.

These days, a large number of buyers are coming in with a cash offer, which in former times was considered very appealing to sellers. However, preapproval helps equalize buyers, and as one seller noted, “I don’t care if it’s cash or mortgage, as long as I get the money.”

If, like most homebuyers, you need a mortgage to finance the purchase, having preapproval can provide some assurance to sellers that your offer won’t fall through because you can’t qualify for the mortgage you expected. Once you’ve received preapproval, don’t open any new credit accounts. If your credit score goes down, the amount you can borrow could decline as well.
 

6. Firm up your budget.

While the preapproval process will tell you how much a lender thinks you can afford, it typically makes sense to come up with your own budget as well. That’s because banks and other mortgage lenders may approve you for much more than you want or are able to pay for a home.

You’ll want to factor in future costs of homeowners as well as any other (current or future) expenses for which the lender may not have accounted. For example, if you’re planning to have children soon, you may want to lower your budget to factor in the cost of childcare.

Knowing your budget ahead of time, and looking only at houses that fall within it, will prevent you from falling in love with a house that you really can’t afford.
 

7. Stick with it.

Buying a house in today’s market is no easy task. The first part of the process requires simply looking at multiple houses to get a sense of how far your budget will go and whether there are homes that meet your requirements.

If you’re sure that purchasing a home is the best financial move for you, don’t give up. Instead, consider whether you can make adjustments that could widen your pool of potential homes. That may mean changing your budget, moving a little further out geographically, or opting for a house that needs a little more work than you expected.

That said, while the pace of price increases will likely moderate, it’s unlikely prices will go down significantly in the future.

“We might see home price appreciation subside to levels close to 10% to 15% [from 20% last year] or even just 5% to 10%,” Ms. Losey says. “When you do the math, home prices just can’t continue to go up 20% year over year.”

Dr. Kobe is planning to keep looking for his home for at least the next several months.

“Prices are still going up, but we are hearing that the inventory will increase over the summer,” he says. “I’m still out looking for the right house, and I’m ready to make an offer.”

A version of this article first appeared on Medscape.com.

After more than a decade of moving because of medical school, residencies, and international fellowships, Abhi Kole, MD, PhD, is ready to put down roots. But he’s learning that buying a house in today’s housing market is easier said than done.

In the past 6 months, Dr. Kole, an internist at Grady Hospital in Atlanta, put in offers on three houses. None resulted in a purchase. Dr. Kole says he’s learned how to be more competitive with each subsequent offer, starting out with a bid significantly above the asking price and waiving his right to an appraisal or financing contingencies.

The experience has been surprising and disappointing.

“I knew the market was bad when I started looking and that home prices had gone up,” Dr. Kole says. “What I didn’t realize was that it would still be so hard for me. I have a good job, no debt, and great credit.”

Another frustration for Dr. Kole: He’s been approved for a physician’s loan (a type of mortgage that requires a lower down payment and does not count student loans in debt-to-income calculations) from a national bank, but sellers seem to prefer buyers who work with local lenders. Dr. Kole has been willing to waive the appraisal and mortgage contingency on the right home, but he draws the line at waiving the inspection, a trend that some other buyers in his area are going along with.

“With each house, I learn more about how this works and what amount of risk I can safely assume,” Dr. Kobe says. “There are certain things I definitely wouldn’t give up.”

Dr. Kole’s experience mirrors that of millions of other would-be homebuyers navigating a strong seller’s market.

“Potential homebuyers are really facing a triple threat right now,” says Clare Losey, an assistant research economist with the Texas Real Estate Research Center. “There’s high home appreciation, high mortgage rates, and low inventory of homes for sale.”

It’s still possible to find — and buy — your dream home, even in today’s market with all its challenges. Here are some important steps that can help you.
 

1. Do not low ball.

There may be some cases in which you can save money by making an offer significantly below the asking price on a property. However, with most housing areas across the country experiencing a seller’s market, you run the risk of offending the buyer or being dismissed as not having a serious offer.

In today’s market, a better strategy is to go in with close to your best and final offer from the start, realtors say. It can help to waive the appraisal or financing contingency as well, although it’s important to understand the risk associated with doing so. Last month, the average home sold for 103% of the list price, according to data compiled from Statista.
 

2. Get credit ready.

The better your credit, the easier time you’ll have getting a mortgage — and the lower the rate you’ll pay for the loan. The average first-time homebuyer has a credit score of 746, according to a recent paper by Fannie Mae. If you know you’re going to buy a home in the next few months, you can improve your credit by making sure to pay all your bills on time and by avoiding taking on any new debt.

This is also a good opportunity to check your credit report (get all three reports for free from AnnualCreditReport.com) to see whether there are any mistakes or other problems that you’ll need to clear up before applying for a loan. Also, take a look at your credit-utilization ratio (the amount of credit you use compared to the amount available to you). Experts recommend keeping this number below 30%.
 

3. Prepare to move quickly.

Among homes that closed in March, the average number of days on the market (the amount of time between listing and closing) was just 38 days, according to Realtor.com. In busy markets, homes are moving even faster, realtors say, with sellers commonly accepting offers within days of listing their house for sale.

“It’s crazy,” says Sarah Scattini, president of the Reno/Sparks Association of Realtors. “The market is moving extremely fast here. If you list your home, your sale is pending within 5 days.”

In addition to moving quickly to make your initial offer, do the same if a buyer counters with a negotiation. A speedy response will show the buyer that you’re very interested — and to beat out any other bidders who may have also received a counteroffer.
 

4. Shop around for mortgages.

Especially for first-time homebuyers, the process will go much more smoothly if you’ve got a team of professionals to help you. Look for a realtor and a mortgage lender who have experience working with first-time homebuyers and with physicians, if possible.

Since mortgage rates can vary wildly, you’ll want to shop around a bit before settling on a lender. Get quotes from a local lender, an online lender, and, potentially, a credit union or a mortgage broker to get a sense of the types of mortgages and rates available to you.

“With multiple offers on every single listing, you really want to align yourself with a great realtor who can negotiate for you on your behalf and navigate you through this very tricky market,” says Ms. Scattini.

For both your realtor and your lender, you’ll want to know up front how they get paid and how they calculate their fees. Typically, the real estate agents for buyers and sellers split a 6% commission on home sales, meaning that your realtor will likely take home 3% of the purchase price.
 

5. Get preapproved.

Once you’ve settled on a lender, getting preapproved for a mortgage can make your offer more appealing to potential buyers. Preapproval is an in-depth process in which lenders pull your credit and look at other financial factors, such as your income and assets, to tell you ahead of time how much you could borrow under their standards and how much that might cost you.

These days, a large number of buyers are coming in with a cash offer, which in former times was considered very appealing to sellers. However, preapproval helps equalize buyers, and as one seller noted, “I don’t care if it’s cash or mortgage, as long as I get the money.”

If, like most homebuyers, you need a mortgage to finance the purchase, having preapproval can provide some assurance to sellers that your offer won’t fall through because you can’t qualify for the mortgage you expected. Once you’ve received preapproval, don’t open any new credit accounts. If your credit score goes down, the amount you can borrow could decline as well.
 

6. Firm up your budget.

While the preapproval process will tell you how much a lender thinks you can afford, it typically makes sense to come up with your own budget as well. That’s because banks and other mortgage lenders may approve you for much more than you want or are able to pay for a home.

You’ll want to factor in future costs of homeowners as well as any other (current or future) expenses for which the lender may not have accounted. For example, if you’re planning to have children soon, you may want to lower your budget to factor in the cost of childcare.

Knowing your budget ahead of time, and looking only at houses that fall within it, will prevent you from falling in love with a house that you really can’t afford.
 

7. Stick with it.

Buying a house in today’s market is no easy task. The first part of the process requires simply looking at multiple houses to get a sense of how far your budget will go and whether there are homes that meet your requirements.

If you’re sure that purchasing a home is the best financial move for you, don’t give up. Instead, consider whether you can make adjustments that could widen your pool of potential homes. That may mean changing your budget, moving a little further out geographically, or opting for a house that needs a little more work than you expected.

That said, while the pace of price increases will likely moderate, it’s unlikely prices will go down significantly in the future.

“We might see home price appreciation subside to levels close to 10% to 15% [from 20% last year] or even just 5% to 10%,” Ms. Losey says. “When you do the math, home prices just can’t continue to go up 20% year over year.”

Dr. Kobe is planning to keep looking for his home for at least the next several months.

“Prices are still going up, but we are hearing that the inventory will increase over the summer,” he says. “I’m still out looking for the right house, and I’m ready to make an offer.”

A version of this article first appeared on Medscape.com.

After more than a decade of moving because of medical school, residencies, and international fellowships, Abhi Kole, MD, PhD, is ready to put down roots. But he’s learning that buying a house in today’s housing market is easier said than done.

In the past 6 months, Dr. Kole, an internist at Grady Hospital in Atlanta, put in offers on three houses. None resulted in a purchase. Dr. Kole says he’s learned how to be more competitive with each subsequent offer, starting out with a bid significantly above the asking price and waiving his right to an appraisal or financing contingencies.

The experience has been surprising and disappointing.

“I knew the market was bad when I started looking and that home prices had gone up,” Dr. Kole says. “What I didn’t realize was that it would still be so hard for me. I have a good job, no debt, and great credit.”

Another frustration for Dr. Kole: He’s been approved for a physician’s loan (a type of mortgage that requires a lower down payment and does not count student loans in debt-to-income calculations) from a national bank, but sellers seem to prefer buyers who work with local lenders. Dr. Kole has been willing to waive the appraisal and mortgage contingency on the right home, but he draws the line at waiving the inspection, a trend that some other buyers in his area are going along with.

“With each house, I learn more about how this works and what amount of risk I can safely assume,” Dr. Kobe says. “There are certain things I definitely wouldn’t give up.”

Dr. Kole’s experience mirrors that of millions of other would-be homebuyers navigating a strong seller’s market.

“Potential homebuyers are really facing a triple threat right now,” says Clare Losey, an assistant research economist with the Texas Real Estate Research Center. “There’s high home appreciation, high mortgage rates, and low inventory of homes for sale.”

It’s still possible to find — and buy — your dream home, even in today’s market with all its challenges. Here are some important steps that can help you.
 

1. Do not low ball.

There may be some cases in which you can save money by making an offer significantly below the asking price on a property. However, with most housing areas across the country experiencing a seller’s market, you run the risk of offending the buyer or being dismissed as not having a serious offer.

In today’s market, a better strategy is to go in with close to your best and final offer from the start, realtors say. It can help to waive the appraisal or financing contingency as well, although it’s important to understand the risk associated with doing so. Last month, the average home sold for 103% of the list price, according to data compiled from Statista.
 

2. Get credit ready.

The better your credit, the easier time you’ll have getting a mortgage — and the lower the rate you’ll pay for the loan. The average first-time homebuyer has a credit score of 746, according to a recent paper by Fannie Mae. If you know you’re going to buy a home in the next few months, you can improve your credit by making sure to pay all your bills on time and by avoiding taking on any new debt.

This is also a good opportunity to check your credit report (get all three reports for free from AnnualCreditReport.com) to see whether there are any mistakes or other problems that you’ll need to clear up before applying for a loan. Also, take a look at your credit-utilization ratio (the amount of credit you use compared to the amount available to you). Experts recommend keeping this number below 30%.
 

3. Prepare to move quickly.

Among homes that closed in March, the average number of days on the market (the amount of time between listing and closing) was just 38 days, according to Realtor.com. In busy markets, homes are moving even faster, realtors say, with sellers commonly accepting offers within days of listing their house for sale.

“It’s crazy,” says Sarah Scattini, president of the Reno/Sparks Association of Realtors. “The market is moving extremely fast here. If you list your home, your sale is pending within 5 days.”

In addition to moving quickly to make your initial offer, do the same if a buyer counters with a negotiation. A speedy response will show the buyer that you’re very interested — and to beat out any other bidders who may have also received a counteroffer.
 

4. Shop around for mortgages.

Especially for first-time homebuyers, the process will go much more smoothly if you’ve got a team of professionals to help you. Look for a realtor and a mortgage lender who have experience working with first-time homebuyers and with physicians, if possible.

Since mortgage rates can vary wildly, you’ll want to shop around a bit before settling on a lender. Get quotes from a local lender, an online lender, and, potentially, a credit union or a mortgage broker to get a sense of the types of mortgages and rates available to you.

“With multiple offers on every single listing, you really want to align yourself with a great realtor who can negotiate for you on your behalf and navigate you through this very tricky market,” says Ms. Scattini.

For both your realtor and your lender, you’ll want to know up front how they get paid and how they calculate their fees. Typically, the real estate agents for buyers and sellers split a 6% commission on home sales, meaning that your realtor will likely take home 3% of the purchase price.
 

5. Get preapproved.

Once you’ve settled on a lender, getting preapproved for a mortgage can make your offer more appealing to potential buyers. Preapproval is an in-depth process in which lenders pull your credit and look at other financial factors, such as your income and assets, to tell you ahead of time how much you could borrow under their standards and how much that might cost you.

These days, a large number of buyers are coming in with a cash offer, which in former times was considered very appealing to sellers. However, preapproval helps equalize buyers, and as one seller noted, “I don’t care if it’s cash or mortgage, as long as I get the money.”

If, like most homebuyers, you need a mortgage to finance the purchase, having preapproval can provide some assurance to sellers that your offer won’t fall through because you can’t qualify for the mortgage you expected. Once you’ve received preapproval, don’t open any new credit accounts. If your credit score goes down, the amount you can borrow could decline as well.
 

6. Firm up your budget.

While the preapproval process will tell you how much a lender thinks you can afford, it typically makes sense to come up with your own budget as well. That’s because banks and other mortgage lenders may approve you for much more than you want or are able to pay for a home.

You’ll want to factor in future costs of homeowners as well as any other (current or future) expenses for which the lender may not have accounted. For example, if you’re planning to have children soon, you may want to lower your budget to factor in the cost of childcare.

Knowing your budget ahead of time, and looking only at houses that fall within it, will prevent you from falling in love with a house that you really can’t afford.
 

7. Stick with it.

Buying a house in today’s market is no easy task. The first part of the process requires simply looking at multiple houses to get a sense of how far your budget will go and whether there are homes that meet your requirements.

If you’re sure that purchasing a home is the best financial move for you, don’t give up. Instead, consider whether you can make adjustments that could widen your pool of potential homes. That may mean changing your budget, moving a little further out geographically, or opting for a house that needs a little more work than you expected.

That said, while the pace of price increases will likely moderate, it’s unlikely prices will go down significantly in the future.

“We might see home price appreciation subside to levels close to 10% to 15% [from 20% last year] or even just 5% to 10%,” Ms. Losey says. “When you do the math, home prices just can’t continue to go up 20% year over year.”

Dr. Kobe is planning to keep looking for his home for at least the next several months.

“Prices are still going up, but we are hearing that the inventory will increase over the summer,” he says. “I’m still out looking for the right house, and I’m ready to make an offer.”

A version of this article first appeared on Medscape.com.