We previously identified key domains of attending attributes for successful rounds¹ and adapted them to represent the trainees’ perspective: Teaching Process (eg, sharing decision-making process, physical exam skills), Learning Environment (eg, being approachable, respectful), Role Modeling (eg, teaching by example, bedside manner), and Team Management (eg, efficiency, providing autonomy). Though all domains are necessary, the relative importance may change in response to external pressures. Inpatient service demands and time constraints fluctuate daily due to patient admissions and discharges, educational conference schedules, and concurrent outpatient clinic responsibilities.^2–4 Furthermore, the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour rules placed greater time pressure on inpatient ward attending rounds.⁵ It is plausible that these pressures affect trainees’ needs and priorities during rounds.

Therefore, we sought to refine our understanding of the learners’ needs during ward rounds. Because we were interested in the contextual influences of trainee characteristics and workload on their preferences, we used the principles of ecological momentary assessment (EMA) to design a novel system to assess daily changes in trainee priorities and associated workload.

Design, Participants, and Setting

In a prospective observational study, we assessed trainee priorities during inpatient rounds. Participants included third- and fourth-year medical students in the University of Alabama at Birmingham (UAB) School of Medicine (Birmingham campus) and residents in the Tinsley Harrison Internal Medicine Residency Training Program assigned to inpatient general medicine ward services from September 2010 to February 2011 (except from December 20, 2010, to January 3, 2011). Three training sites were included in this study: UAB Hospital (>1000-bed, university-based hospital), Birmingham Veterans Affairs Medical Center (300-bed), and Cooper Green Hospital (40-bed county hospital). Each site housed 4 or 5 general medicine ward teams, composed of 1–3 medical students (third or fourth year), 2 first-year residents, 1 upper level resident (postgraduate year 2–4), and 1 attending physician.

Assessment

Our original domains of attending rounds were derived from groupings and ratings of specific teaching characteristics by attending physicians, residents, and students.¹ However, because our goal was to understand the learners’ perspective of successful ward rounds, we revised these domains by limiting the algorithm to data on groupings and ratings by residents and students only. This process resulted in the domains used in this study (Appendix).

We used EMA principles to create a novel system to assess daily variation in trainees’ prioritization of these domains and workload.^6,7 EMA-derived assessment tools collect data frequently (several times per week, up to multiple times per day) to identify time-sensitive fluctuations. We designed a pocket-sized daily assessment card for trainees to complete each day after rounds (Figure 1). Trainees were asked to indicate the most important domain for successful ward rounds to them that day and provide individual characteristics (ie, sex and training level) and data on factors we hypothesized were related to perceived work load (ie, patient census, day of call cycle, and number of team members absent on rounds that day). We anticipated the Expectations domain would not be responsive to daily changes in workload because expectations are usually set once on the first day of the rotation, and thus we did not include this domain in our final assessment tool. Assessment cards and locked receptacles were kept in team workrooms for ease of accessibility; cards were collected twice monthly. All data were anonymous.

Analysis

Our unit of analysis was the EMA card. We examined associations between daily domain priority with respondent demographics and workload information using Pearson’s chi-squared analyses, adjusted for clustering effects by team. α was set at 0.05. All analyses were performed by using Stata 13.0 (Stata Statistical Software: Release 13; College Station, TX).

Sex and training level were associated with prioritization of teaching domains. Male trainees were more likely to choose Team Management (P = 0.01) or Teaching Process (P = 0.04) as their preferred domain. Medical students valued Teaching Process 42% of the time, compared with 23% for interns and 21% for upper level residents (P = 0.005). The opposite trend emerged for Team Management: as training level increased, the importance of Team Management increased (P < 0.001). There were no significant trends by training level for the Role Modeling and Learning Environment domains.

Domain priority was also associated with workload characteristics. On post-call days, Team Management (P < 0.001) was more likely to be selected as the most important domain, but on other days, Teaching Process (P = 0.005) was more often selected (Figure 2). Trainees also selected Team Management as the most important domain with an increasing number of team members absent (P = 0.001), and as the teams’ overall patient census increased (P < 0.001). The Learning Environment and Role Modeling domains’ importance did not vary by call-day or patient census.

We used a novel approach to assess contextual factors affecting trainee prioritization of 4 domains that contribute to successful inpatient internal medicine attending rounds. We found training level and workload demands were associated with prioritization of teaching domains. Prioritization of Teaching Process, exemplified by setting aside time to teach, demonstrating physical exam skills, and clear delineation of the attending’s thought process, was inversely associated with training level. On the days with highest workload, Team Management was most likely to be prioritized. Our findings suggest that attending physicians should consider adapting rounding style based on team members’ training levels and workload.

Prior work has described teaching and rounding styles, influences, and priorities in response to workload from the attending physician’s perspective,^8–11 and our study extends these reports by providing the complementary perspective of trainees. On days with high workload, trainees prefer the Team Management domain, characterized by organized and efficient rounds, agreement on a clear and consistent plan of care, and being allowed independence and time during rounds to meet other responsibilities.¹ These findings support an “empowerment style,” defined by Goldszmidt et al. as using integrated teaching and oversight strategies to support trainees’ progressive independence.⁹ Though some attending physicians report shifting to a more direct patient care style on days with a high patient census,⁹ our results suggest that learners instead prefer more independence, being empowered to perform more direct care. While there is an increasing pressure to heighten attending supervision due to concerns about patient safety, restricted work hours, and litigation,¹² trainees value being part of the care process and being included as integral members of the care team, which may actually mitigate patient safety risks.⁸

Our results are consistent with prior studies, reporting that learners at different levels of training have different instructional needs: medical students seek more teaching, and senior residents sought an efficient leader.^13,14 Taken together, these studies suggest that attending physicians should tailor rounds to the level of the trainee. For example, it may be beneficial for the attending physician to spend time outside of rounds with students to teach medical knowledge. During rounds, the entire group benefits most from modeling clinical reasoning, discussing new medical evidence, and demonstrating communication skills and leadership.

Our study has limitations. Though our study was performed before the 2011 ACGME duty hour restrictions,⁵ our results are likely of greater importance and relevance, as our findings ultimately highlight the competing demands of time vs duty. Also, while our study was performed at a single institution, potentially limiting generalizability, we included 3 types of training hospitals, a university, veterans and a county hospital, and found no differences between sites. Additionally, we collected over 1,000 cards over the course of 6 months, assessing rounds of over 50 different attending physicians, suggesting broader applicability. Our overall response rate was low, a typical signal for respondent bias, but because we collected daily assessments, standard interpretation of response rates referring to a one-time survey do not apply.¹⁵ We believe we achieved an adequate sample, as the majority of teams participated, the respondent demographics were proportional to the base population eligible to participate, and we received a similar number of cards on all months. Finally, although we were unable to account for clustering effects by individual respondents because response cards were anonymous, we adjusted for clustering effects by team.

Attending physicians may use our findings to adapt teaching techniques to appeal to specific training levels and to external pressures during teaching rounds. Focusing and investing time in teaching medical knowledge and clinical reasoning tailored to each level of learner is paramount on most days. However, days with a high workload may require emphasis on delegating clear, rational treatment plans, when learners are less receptive to traditional didactic methods.

Disclosure

An abstract based on the current analysis was presented at the Society of General Internal Medicine 34th Annual Meeting, April 2011, Phoenix, AZ. Dr. Brita Roy is supported by grant number K12HS023000 from the Agency for Healthcare Research and Quality. The authors have no conflicts to disclose. The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs or the Agency for Healthcare Research and Quality.

We previously identified key domains of attending attributes for successful rounds¹ and adapted them to represent the trainees’ perspective: Teaching Process (eg, sharing decision-making process, physical exam skills), Learning Environment (eg, being approachable, respectful), Role Modeling (eg, teaching by example, bedside manner), and Team Management (eg, efficiency, providing autonomy). Though all domains are necessary, the relative importance may change in response to external pressures. Inpatient service demands and time constraints fluctuate daily due to patient admissions and discharges, educational conference schedules, and concurrent outpatient clinic responsibilities.^2–4 Furthermore, the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour rules placed greater time pressure on inpatient ward attending rounds.⁵ It is plausible that these pressures affect trainees’ needs and priorities during rounds.

Therefore, we sought to refine our understanding of the learners’ needs during ward rounds. Because we were interested in the contextual influences of trainee characteristics and workload on their preferences, we used the principles of ecological momentary assessment (EMA) to design a novel system to assess daily changes in trainee priorities and associated workload.

Design, Participants, and Setting

In a prospective observational study, we assessed trainee priorities during inpatient rounds. Participants included third- and fourth-year medical students in the University of Alabama at Birmingham (UAB) School of Medicine (Birmingham campus) and residents in the Tinsley Harrison Internal Medicine Residency Training Program assigned to inpatient general medicine ward services from September 2010 to February 2011 (except from December 20, 2010, to January 3, 2011). Three training sites were included in this study: UAB Hospital (>1000-bed, university-based hospital), Birmingham Veterans Affairs Medical Center (300-bed), and Cooper Green Hospital (40-bed county hospital). Each site housed 4 or 5 general medicine ward teams, composed of 1–3 medical students (third or fourth year), 2 first-year residents, 1 upper level resident (postgraduate year 2–4), and 1 attending physician.

Assessment

Our original domains of attending rounds were derived from groupings and ratings of specific teaching characteristics by attending physicians, residents, and students.¹ However, because our goal was to understand the learners’ perspective of successful ward rounds, we revised these domains by limiting the algorithm to data on groupings and ratings by residents and students only. This process resulted in the domains used in this study (Appendix).

We used EMA principles to create a novel system to assess daily variation in trainees’ prioritization of these domains and workload.^6,7 EMA-derived assessment tools collect data frequently (several times per week, up to multiple times per day) to identify time-sensitive fluctuations. We designed a pocket-sized daily assessment card for trainees to complete each day after rounds (Figure 1). Trainees were asked to indicate the most important domain for successful ward rounds to them that day and provide individual characteristics (ie, sex and training level) and data on factors we hypothesized were related to perceived work load (ie, patient census, day of call cycle, and number of team members absent on rounds that day). We anticipated the Expectations domain would not be responsive to daily changes in workload because expectations are usually set once on the first day of the rotation, and thus we did not include this domain in our final assessment tool. Assessment cards and locked receptacles were kept in team workrooms for ease of accessibility; cards were collected twice monthly. All data were anonymous.

Analysis

Our unit of analysis was the EMA card. We examined associations between daily domain priority with respondent demographics and workload information using Pearson’s chi-squared analyses, adjusted for clustering effects by team. α was set at 0.05. All analyses were performed by using Stata 13.0 (Stata Statistical Software: Release 13; College Station, TX).

Sex and training level were associated with prioritization of teaching domains. Male trainees were more likely to choose Team Management (P = 0.01) or Teaching Process (P = 0.04) as their preferred domain. Medical students valued Teaching Process 42% of the time, compared with 23% for interns and 21% for upper level residents (P = 0.005). The opposite trend emerged for Team Management: as training level increased, the importance of Team Management increased (P < 0.001). There were no significant trends by training level for the Role Modeling and Learning Environment domains.

Domain priority was also associated with workload characteristics. On post-call days, Team Management (P < 0.001) was more likely to be selected as the most important domain, but on other days, Teaching Process (P = 0.005) was more often selected (Figure 2). Trainees also selected Team Management as the most important domain with an increasing number of team members absent (P = 0.001), and as the teams’ overall patient census increased (P < 0.001). The Learning Environment and Role Modeling domains’ importance did not vary by call-day or patient census.

We used a novel approach to assess contextual factors affecting trainee prioritization of 4 domains that contribute to successful inpatient internal medicine attending rounds. We found training level and workload demands were associated with prioritization of teaching domains. Prioritization of Teaching Process, exemplified by setting aside time to teach, demonstrating physical exam skills, and clear delineation of the attending’s thought process, was inversely associated with training level. On the days with highest workload, Team Management was most likely to be prioritized. Our findings suggest that attending physicians should consider adapting rounding style based on team members’ training levels and workload.

Prior work has described teaching and rounding styles, influences, and priorities in response to workload from the attending physician’s perspective,^8–11 and our study extends these reports by providing the complementary perspective of trainees. On days with high workload, trainees prefer the Team Management domain, characterized by organized and efficient rounds, agreement on a clear and consistent plan of care, and being allowed independence and time during rounds to meet other responsibilities.¹ These findings support an “empowerment style,” defined by Goldszmidt et al. as using integrated teaching and oversight strategies to support trainees’ progressive independence.⁹ Though some attending physicians report shifting to a more direct patient care style on days with a high patient census,⁹ our results suggest that learners instead prefer more independence, being empowered to perform more direct care. While there is an increasing pressure to heighten attending supervision due to concerns about patient safety, restricted work hours, and litigation,¹² trainees value being part of the care process and being included as integral members of the care team, which may actually mitigate patient safety risks.⁸

Our results are consistent with prior studies, reporting that learners at different levels of training have different instructional needs: medical students seek more teaching, and senior residents sought an efficient leader.^13,14 Taken together, these studies suggest that attending physicians should tailor rounds to the level of the trainee. For example, it may be beneficial for the attending physician to spend time outside of rounds with students to teach medical knowledge. During rounds, the entire group benefits most from modeling clinical reasoning, discussing new medical evidence, and demonstrating communication skills and leadership.

Our study has limitations. Though our study was performed before the 2011 ACGME duty hour restrictions,⁵ our results are likely of greater importance and relevance, as our findings ultimately highlight the competing demands of time vs duty. Also, while our study was performed at a single institution, potentially limiting generalizability, we included 3 types of training hospitals, a university, veterans and a county hospital, and found no differences between sites. Additionally, we collected over 1,000 cards over the course of 6 months, assessing rounds of over 50 different attending physicians, suggesting broader applicability. Our overall response rate was low, a typical signal for respondent bias, but because we collected daily assessments, standard interpretation of response rates referring to a one-time survey do not apply.¹⁵ We believe we achieved an adequate sample, as the majority of teams participated, the respondent demographics were proportional to the base population eligible to participate, and we received a similar number of cards on all months. Finally, although we were unable to account for clustering effects by individual respondents because response cards were anonymous, we adjusted for clustering effects by team.

Attending physicians may use our findings to adapt teaching techniques to appeal to specific training levels and to external pressures during teaching rounds. Focusing and investing time in teaching medical knowledge and clinical reasoning tailored to each level of learner is paramount on most days. However, days with a high workload may require emphasis on delegating clear, rational treatment plans, when learners are less receptive to traditional didactic methods.

Disclosure

An abstract based on the current analysis was presented at the Society of General Internal Medicine 34th Annual Meeting, April 2011, Phoenix, AZ. Dr. Brita Roy is supported by grant number K12HS023000 from the Agency for Healthcare Research and Quality. The authors have no conflicts to disclose. The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs or the Agency for Healthcare Research and Quality.

We previously identified key domains of attending attributes for successful rounds¹ and adapted them to represent the trainees’ perspective: Teaching Process (eg, sharing decision-making process, physical exam skills), Learning Environment (eg, being approachable, respectful), Role Modeling (eg, teaching by example, bedside manner), and Team Management (eg, efficiency, providing autonomy). Though all domains are necessary, the relative importance may change in response to external pressures. Inpatient service demands and time constraints fluctuate daily due to patient admissions and discharges, educational conference schedules, and concurrent outpatient clinic responsibilities.^2–4 Furthermore, the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour rules placed greater time pressure on inpatient ward attending rounds.⁵ It is plausible that these pressures affect trainees’ needs and priorities during rounds.

Therefore, we sought to refine our understanding of the learners’ needs during ward rounds. Because we were interested in the contextual influences of trainee characteristics and workload on their preferences, we used the principles of ecological momentary assessment (EMA) to design a novel system to assess daily changes in trainee priorities and associated workload.

Design, Participants, and Setting

In a prospective observational study, we assessed trainee priorities during inpatient rounds. Participants included third- and fourth-year medical students in the University of Alabama at Birmingham (UAB) School of Medicine (Birmingham campus) and residents in the Tinsley Harrison Internal Medicine Residency Training Program assigned to inpatient general medicine ward services from September 2010 to February 2011 (except from December 20, 2010, to January 3, 2011). Three training sites were included in this study: UAB Hospital (>1000-bed, university-based hospital), Birmingham Veterans Affairs Medical Center (300-bed), and Cooper Green Hospital (40-bed county hospital). Each site housed 4 or 5 general medicine ward teams, composed of 1–3 medical students (third or fourth year), 2 first-year residents, 1 upper level resident (postgraduate year 2–4), and 1 attending physician.

Assessment

Our original domains of attending rounds were derived from groupings and ratings of specific teaching characteristics by attending physicians, residents, and students.¹ However, because our goal was to understand the learners’ perspective of successful ward rounds, we revised these domains by limiting the algorithm to data on groupings and ratings by residents and students only. This process resulted in the domains used in this study (Appendix).

We used EMA principles to create a novel system to assess daily variation in trainees’ prioritization of these domains and workload.^6,7 EMA-derived assessment tools collect data frequently (several times per week, up to multiple times per day) to identify time-sensitive fluctuations. We designed a pocket-sized daily assessment card for trainees to complete each day after rounds (Figure 1). Trainees were asked to indicate the most important domain for successful ward rounds to them that day and provide individual characteristics (ie, sex and training level) and data on factors we hypothesized were related to perceived work load (ie, patient census, day of call cycle, and number of team members absent on rounds that day). We anticipated the Expectations domain would not be responsive to daily changes in workload because expectations are usually set once on the first day of the rotation, and thus we did not include this domain in our final assessment tool. Assessment cards and locked receptacles were kept in team workrooms for ease of accessibility; cards were collected twice monthly. All data were anonymous.

Analysis

Our unit of analysis was the EMA card. We examined associations between daily domain priority with respondent demographics and workload information using Pearson’s chi-squared analyses, adjusted for clustering effects by team. α was set at 0.05. All analyses were performed by using Stata 13.0 (Stata Statistical Software: Release 13; College Station, TX).

Sex and training level were associated with prioritization of teaching domains. Male trainees were more likely to choose Team Management (P = 0.01) or Teaching Process (P = 0.04) as their preferred domain. Medical students valued Teaching Process 42% of the time, compared with 23% for interns and 21% for upper level residents (P = 0.005). The opposite trend emerged for Team Management: as training level increased, the importance of Team Management increased (P < 0.001). There were no significant trends by training level for the Role Modeling and Learning Environment domains.

Domain priority was also associated with workload characteristics. On post-call days, Team Management (P < 0.001) was more likely to be selected as the most important domain, but on other days, Teaching Process (P = 0.005) was more often selected (Figure 2). Trainees also selected Team Management as the most important domain with an increasing number of team members absent (P = 0.001), and as the teams’ overall patient census increased (P < 0.001). The Learning Environment and Role Modeling domains’ importance did not vary by call-day or patient census.

We used a novel approach to assess contextual factors affecting trainee prioritization of 4 domains that contribute to successful inpatient internal medicine attending rounds. We found training level and workload demands were associated with prioritization of teaching domains. Prioritization of Teaching Process, exemplified by setting aside time to teach, demonstrating physical exam skills, and clear delineation of the attending’s thought process, was inversely associated with training level. On the days with highest workload, Team Management was most likely to be prioritized. Our findings suggest that attending physicians should consider adapting rounding style based on team members’ training levels and workload.

Prior work has described teaching and rounding styles, influences, and priorities in response to workload from the attending physician’s perspective,^8–11 and our study extends these reports by providing the complementary perspective of trainees. On days with high workload, trainees prefer the Team Management domain, characterized by organized and efficient rounds, agreement on a clear and consistent plan of care, and being allowed independence and time during rounds to meet other responsibilities.¹ These findings support an “empowerment style,” defined by Goldszmidt et al. as using integrated teaching and oversight strategies to support trainees’ progressive independence.⁹ Though some attending physicians report shifting to a more direct patient care style on days with a high patient census,⁹ our results suggest that learners instead prefer more independence, being empowered to perform more direct care. While there is an increasing pressure to heighten attending supervision due to concerns about patient safety, restricted work hours, and litigation,¹² trainees value being part of the care process and being included as integral members of the care team, which may actually mitigate patient safety risks.⁸

Our results are consistent with prior studies, reporting that learners at different levels of training have different instructional needs: medical students seek more teaching, and senior residents sought an efficient leader.^13,14 Taken together, these studies suggest that attending physicians should tailor rounds to the level of the trainee. For example, it may be beneficial for the attending physician to spend time outside of rounds with students to teach medical knowledge. During rounds, the entire group benefits most from modeling clinical reasoning, discussing new medical evidence, and demonstrating communication skills and leadership.

Our study has limitations. Though our study was performed before the 2011 ACGME duty hour restrictions,⁵ our results are likely of greater importance and relevance, as our findings ultimately highlight the competing demands of time vs duty. Also, while our study was performed at a single institution, potentially limiting generalizability, we included 3 types of training hospitals, a university, veterans and a county hospital, and found no differences between sites. Additionally, we collected over 1,000 cards over the course of 6 months, assessing rounds of over 50 different attending physicians, suggesting broader applicability. Our overall response rate was low, a typical signal for respondent bias, but because we collected daily assessments, standard interpretation of response rates referring to a one-time survey do not apply.¹⁵ We believe we achieved an adequate sample, as the majority of teams participated, the respondent demographics were proportional to the base population eligible to participate, and we received a similar number of cards on all months. Finally, although we were unable to account for clustering effects by individual respondents because response cards were anonymous, we adjusted for clustering effects by team.

Attending physicians may use our findings to adapt teaching techniques to appeal to specific training levels and to external pressures during teaching rounds. Focusing and investing time in teaching medical knowledge and clinical reasoning tailored to each level of learner is paramount on most days. However, days with a high workload may require emphasis on delegating clear, rational treatment plans, when learners are less receptive to traditional didactic methods.

Disclosure

An abstract based on the current analysis was presented at the Society of General Internal Medicine 34th Annual Meeting, April 2011, Phoenix, AZ. Dr. Brita Roy is supported by grant number K12HS023000 from the Agency for Healthcare Research and Quality. The authors have no conflicts to disclose. The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs or the Agency for Healthcare Research and Quality.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Micrograph showing DLBCL

The European Medicines Agency (EMA) has granted polatuzumab vedotin access to the agency’s PRIority MEdicines (PRIME) program.

The access is for polatuzumab vedotin when used in combination with rituximab and bendamustine for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Polatuzumab vedotin is an anti-CD79b antibody drug conjugate consisting of an anti-CD79b monoclonal antibody that is linked to a microtubule-disrupting agent.

Polatuzumab vedotin is being developed by Roche utilizing Seattle Genetics’ technology.

The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.

Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.

To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.

The acceptance of polatuzumab vedotin in the PRIME program was supported by results from the phase 2 component of the GO29365 study.

Results from this trial were recently presented at the 22nd Congress of the European Hematology Association (EHA) as abstract S468.

Writing for publication fulfills a professional obligation to contribute to the body of knowledge. In the past decade, we’ve seen increases in the number of journals and in the number of NPs and PAs—providing more publishing opportunities and more potential authors. Yet many of my colleagues have little interest in publishing; perhaps they fear the writing process or believe they lack the skills to compose a manuscript.

How, then, do we cajole them into sharing their expertise in written form? Much has been written about why you should write.^1,2 What is needed is guidance on the process to help overcome the common ­barriers to success in publishing. If it’s been a long time since you were in school at all—or at least since you took English Composition 101—allow me to offer a solid starting point for the journey of writing.

A manuscript, in essence, is a collection of paragraphs that follow a traditional flow. But to be sufficiently developed, paragraphs must (1) contain a main idea, (2) be structurally coherent, and (3) maintain a sense of unity around the idea.³ Once authors master the composition of a strong paragraph, the development of the manuscript comes naturally. Here are seven tips—four on content development and three on form—for compiling a manuscript worthy of publication and personal pride.

1. Start strong. Everyone understands the importance of grabbing a reader’s attention right out of the gate, right? A strong topic sentence does more than introduce the subject; it sets the tone for those that follow. A short sentence at the beginning of a paragraph establishes an understanding that a discussion will follow—and offers a preview of what the discussion will entail. But writers need not be limited; a topic sentence can take the form of a question or be placed later in the paragraph. Less experienced authors may prefer to open the paragraph with the topic sentence, however, as this allows for a quick assessment of whether the subsequent sentences follow logically. In other words, start simple—there is room to grow as you gain confidence with writing.

2. Use the MEAL plan. A paragraph should extend from the topic sentence. Collectively, the paragraph’s sentences should follow the steps outlined in the “MEAL plan,” a valuable resource conceptualized by the Duke University Thompson Writing Program.⁴ The “M” stands for the main topic; “E,” for the evidence that supports or refutes the topic sentence; “A,” for analysis and its importance; and “L,” for the link back to the larger claim (ie, the overall topic of the paper).

Using the MEAL approach is relatively straightforward. Picture yourself as the sender of a message; the reader is your recipient. You need to convey the information to your reader so that he or she understands it.

Limiting the number of words in a sentence and the number of sentences in a paragraph may help. Exceedingly long sentences are cumbersome and threaten to muddle the author’s message. They also pose the risk for improper noun/verb agreement, irregular punctuation, and hindered readability. (But then, what are editors for?)

A paragraph presents a well-formulated argument; one that contains only two sentences is unlikely to support the author’s assertion. Novice writers, however, often go to the other extreme, which dilutes the point. As a rule of thumb, if you can speak the entire paragraph with a single breath, the length is adequate. Reading your work aloud also helps identify hidden hazards.

3. Make connections. The result would be confusing and nonsensical. Similarly, you wouldn’t conclude your paragraph before you’ve started it. Imagine if you tried to clean out a wound after applying a dressing. The key to a good paragraph is cohesion.

If you’re scratching your head at the previous paragraph, you take my next point: All sentences within a paragraph should have a natural flow. In a well-developed paragraph, each sentence directly relates to the one before and the one after; they work together to convey your point. If the topic sentence contains an assertion, the following sentences provide supporting evidence. In medical writing, this evidence comes from citations to published literature.

If you are using the MEAL plan, you have an outline for how to support your topic sentence in a logical manner. You can then link sentences by capitalizing on words or phrases to form bridges that carry the reader through the paragraph.⁵ These links are created through repetition of key words or through parallel grammatical forms.

4. Pump the brakes. No one likes an abrupt stop. When you’re winding down on a paragraph, you need to signal to the reader that you’re going to shift gears. The last sentence of a paragraph should serve as a natural transition to the next paragraph.⁶ Equally important is the transition line at the beginning of the next paragraph.

Regardless of where the transition occurs, the goal remains to help the reader follow your logic. A subsequent paragraph can extend or refute the argument that has been presented, or it can introduce an entirely new point. No matter what, you want the reader to be prepared for a change in focus and to stay with you through your transition to a new perspective or subtopic.

On the other hand, if the argument is exhausted—it stops. When your discussion is complete, the transition to the next paragraph is very different (eg, “In summary…”). This is an appropriate time to move to a new paragraph and new section.

Speaking of a new section, let’s switch our focus to form.

5. Take action. There are two types of “voice” in communication: active, in which the subject is taking some form of action (eg, You are reading this article), and passive, in which the action is performed upon the subject (eg, This article is being read by you). Active voice is preferred for several reasons—namely, clarity and space. An active sentence identifies who is doing what. The same conclusion may be reached through a passive sentence, with some effort on the reader’s part—but active sentences tend to be more concise. They also convey a sense of immediacy, hopefully drawing the reader into your article.

6. Punctuate like a pro. Punctuation is important! It provides structure, improving clarity and comprehension. Can you fathom the confusion that would occur if an author misused (or failed to use) appropriate punctuation?

Thankfully, rules regarding punctuation have not changed much over the past century. One notable exception is use of the serial (or “Oxford”) comma, which incites passionate debate among both amateur and professional linguists.⁷ (For the record, this publication uses the Oxford comma. Just ask the editors: Karen, Ann, and Amy.)

A full review of punctuation is beyond the scope of this article; however, be it known that the most problematic marks—the ones to double-check in your own writing—are the apostrophe (plural or singular possessive use), the semi-colon, the comma (or lack of), and quotation marks.⁸ To improve your punctuation, obtain a basic grammar handbook or search online.

7. Don’t volley with verbs. Verb tense should remain consistent throughout the paragraph.⁹ Paragraphs with multiple verb tenses bounce the reader’s mind back and forth. It’s like watching a ping pong match, but less enjoyable.

To check for consistency, print the manuscript and mix the order of the pages. Circle the verbs. Look at the circled words and assess the tense of each. Then, repair the damage.

It is easier to identify these types of problems with a manuscript when you’re reading the pages out of order. Editors will tell you that it is difficult to focus on particulars when you are distracted by the content of the paper. Out-of-order pages are harder to read for “sense,” so you can focus on tense, voice, and punctuation.

In conclusion, I hope I’ve helped you see that writing is a process—some say a craft—but it is one that anyone can tackle with the right mindset and preparation. Most authors have a key message; they may just need help expressing it. Starting with small elements, such as the paragraph, helps the author deliver the message clearly.

Writing for publication fulfills a professional obligation to contribute to the body of knowledge. In the past decade, we’ve seen increases in the number of journals and in the number of NPs and PAs—providing more publishing opportunities and more potential authors. Yet many of my colleagues have little interest in publishing; perhaps they fear the writing process or believe they lack the skills to compose a manuscript.

How, then, do we cajole them into sharing their expertise in written form? Much has been written about why you should write.^1,2 What is needed is guidance on the process to help overcome the common ­barriers to success in publishing. If it’s been a long time since you were in school at all—or at least since you took English Composition 101—allow me to offer a solid starting point for the journey of writing.

A manuscript, in essence, is a collection of paragraphs that follow a traditional flow. But to be sufficiently developed, paragraphs must (1) contain a main idea, (2) be structurally coherent, and (3) maintain a sense of unity around the idea.³ Once authors master the composition of a strong paragraph, the development of the manuscript comes naturally. Here are seven tips—four on content development and three on form—for compiling a manuscript worthy of publication and personal pride.

1. Start strong. Everyone understands the importance of grabbing a reader’s attention right out of the gate, right? A strong topic sentence does more than introduce the subject; it sets the tone for those that follow. A short sentence at the beginning of a paragraph establishes an understanding that a discussion will follow—and offers a preview of what the discussion will entail. But writers need not be limited; a topic sentence can take the form of a question or be placed later in the paragraph. Less experienced authors may prefer to open the paragraph with the topic sentence, however, as this allows for a quick assessment of whether the subsequent sentences follow logically. In other words, start simple—there is room to grow as you gain confidence with writing.

2. Use the MEAL plan. A paragraph should extend from the topic sentence. Collectively, the paragraph’s sentences should follow the steps outlined in the “MEAL plan,” a valuable resource conceptualized by the Duke University Thompson Writing Program.⁴ The “M” stands for the main topic; “E,” for the evidence that supports or refutes the topic sentence; “A,” for analysis and its importance; and “L,” for the link back to the larger claim (ie, the overall topic of the paper).

Using the MEAL approach is relatively straightforward. Picture yourself as the sender of a message; the reader is your recipient. You need to convey the information to your reader so that he or she understands it.

Limiting the number of words in a sentence and the number of sentences in a paragraph may help. Exceedingly long sentences are cumbersome and threaten to muddle the author’s message. They also pose the risk for improper noun/verb agreement, irregular punctuation, and hindered readability. (But then, what are editors for?)

A paragraph presents a well-formulated argument; one that contains only two sentences is unlikely to support the author’s assertion. Novice writers, however, often go to the other extreme, which dilutes the point. As a rule of thumb, if you can speak the entire paragraph with a single breath, the length is adequate. Reading your work aloud also helps identify hidden hazards.

3. Make connections. The result would be confusing and nonsensical. Similarly, you wouldn’t conclude your paragraph before you’ve started it. Imagine if you tried to clean out a wound after applying a dressing. The key to a good paragraph is cohesion.

If you’re scratching your head at the previous paragraph, you take my next point: All sentences within a paragraph should have a natural flow. In a well-developed paragraph, each sentence directly relates to the one before and the one after; they work together to convey your point. If the topic sentence contains an assertion, the following sentences provide supporting evidence. In medical writing, this evidence comes from citations to published literature.

If you are using the MEAL plan, you have an outline for how to support your topic sentence in a logical manner. You can then link sentences by capitalizing on words or phrases to form bridges that carry the reader through the paragraph.⁵ These links are created through repetition of key words or through parallel grammatical forms.

4. Pump the brakes. No one likes an abrupt stop. When you’re winding down on a paragraph, you need to signal to the reader that you’re going to shift gears. The last sentence of a paragraph should serve as a natural transition to the next paragraph.⁶ Equally important is the transition line at the beginning of the next paragraph.

Regardless of where the transition occurs, the goal remains to help the reader follow your logic. A subsequent paragraph can extend or refute the argument that has been presented, or it can introduce an entirely new point. No matter what, you want the reader to be prepared for a change in focus and to stay with you through your transition to a new perspective or subtopic.

On the other hand, if the argument is exhausted—it stops. When your discussion is complete, the transition to the next paragraph is very different (eg, “In summary…”). This is an appropriate time to move to a new paragraph and new section.

Speaking of a new section, let’s switch our focus to form.

5. Take action. There are two types of “voice” in communication: active, in which the subject is taking some form of action (eg, You are reading this article), and passive, in which the action is performed upon the subject (eg, This article is being read by you). Active voice is preferred for several reasons—namely, clarity and space. An active sentence identifies who is doing what. The same conclusion may be reached through a passive sentence, with some effort on the reader’s part—but active sentences tend to be more concise. They also convey a sense of immediacy, hopefully drawing the reader into your article.

6. Punctuate like a pro. Punctuation is important! It provides structure, improving clarity and comprehension. Can you fathom the confusion that would occur if an author misused (or failed to use) appropriate punctuation?

Thankfully, rules regarding punctuation have not changed much over the past century. One notable exception is use of the serial (or “Oxford”) comma, which incites passionate debate among both amateur and professional linguists.⁷ (For the record, this publication uses the Oxford comma. Just ask the editors: Karen, Ann, and Amy.)

A full review of punctuation is beyond the scope of this article; however, be it known that the most problematic marks—the ones to double-check in your own writing—are the apostrophe (plural or singular possessive use), the semi-colon, the comma (or lack of), and quotation marks.⁸ To improve your punctuation, obtain a basic grammar handbook or search online.

7. Don’t volley with verbs. Verb tense should remain consistent throughout the paragraph.⁹ Paragraphs with multiple verb tenses bounce the reader’s mind back and forth. It’s like watching a ping pong match, but less enjoyable.

To check for consistency, print the manuscript and mix the order of the pages. Circle the verbs. Look at the circled words and assess the tense of each. Then, repair the damage.

It is easier to identify these types of problems with a manuscript when you’re reading the pages out of order. Editors will tell you that it is difficult to focus on particulars when you are distracted by the content of the paper. Out-of-order pages are harder to read for “sense,” so you can focus on tense, voice, and punctuation.

In conclusion, I hope I’ve helped you see that writing is a process—some say a craft—but it is one that anyone can tackle with the right mindset and preparation. Most authors have a key message; they may just need help expressing it. Starting with small elements, such as the paragraph, helps the author deliver the message clearly.

Writing for publication fulfills a professional obligation to contribute to the body of knowledge. In the past decade, we’ve seen increases in the number of journals and in the number of NPs and PAs—providing more publishing opportunities and more potential authors. Yet many of my colleagues have little interest in publishing; perhaps they fear the writing process or believe they lack the skills to compose a manuscript.

How, then, do we cajole them into sharing their expertise in written form? Much has been written about why you should write.^1,2 What is needed is guidance on the process to help overcome the common ­barriers to success in publishing. If it’s been a long time since you were in school at all—or at least since you took English Composition 101—allow me to offer a solid starting point for the journey of writing.

A manuscript, in essence, is a collection of paragraphs that follow a traditional flow. But to be sufficiently developed, paragraphs must (1) contain a main idea, (2) be structurally coherent, and (3) maintain a sense of unity around the idea.³ Once authors master the composition of a strong paragraph, the development of the manuscript comes naturally. Here are seven tips—four on content development and three on form—for compiling a manuscript worthy of publication and personal pride.

1. Start strong. Everyone understands the importance of grabbing a reader’s attention right out of the gate, right? A strong topic sentence does more than introduce the subject; it sets the tone for those that follow. A short sentence at the beginning of a paragraph establishes an understanding that a discussion will follow—and offers a preview of what the discussion will entail. But writers need not be limited; a topic sentence can take the form of a question or be placed later in the paragraph. Less experienced authors may prefer to open the paragraph with the topic sentence, however, as this allows for a quick assessment of whether the subsequent sentences follow logically. In other words, start simple—there is room to grow as you gain confidence with writing.

2. Use the MEAL plan. A paragraph should extend from the topic sentence. Collectively, the paragraph’s sentences should follow the steps outlined in the “MEAL plan,” a valuable resource conceptualized by the Duke University Thompson Writing Program.⁴ The “M” stands for the main topic; “E,” for the evidence that supports or refutes the topic sentence; “A,” for analysis and its importance; and “L,” for the link back to the larger claim (ie, the overall topic of the paper).

Using the MEAL approach is relatively straightforward. Picture yourself as the sender of a message; the reader is your recipient. You need to convey the information to your reader so that he or she understands it.

Limiting the number of words in a sentence and the number of sentences in a paragraph may help. Exceedingly long sentences are cumbersome and threaten to muddle the author’s message. They also pose the risk for improper noun/verb agreement, irregular punctuation, and hindered readability. (But then, what are editors for?)

A paragraph presents a well-formulated argument; one that contains only two sentences is unlikely to support the author’s assertion. Novice writers, however, often go to the other extreme, which dilutes the point. As a rule of thumb, if you can speak the entire paragraph with a single breath, the length is adequate. Reading your work aloud also helps identify hidden hazards.

3. Make connections. The result would be confusing and nonsensical. Similarly, you wouldn’t conclude your paragraph before you’ve started it. Imagine if you tried to clean out a wound after applying a dressing. The key to a good paragraph is cohesion.

If you’re scratching your head at the previous paragraph, you take my next point: All sentences within a paragraph should have a natural flow. In a well-developed paragraph, each sentence directly relates to the one before and the one after; they work together to convey your point. If the topic sentence contains an assertion, the following sentences provide supporting evidence. In medical writing, this evidence comes from citations to published literature.

If you are using the MEAL plan, you have an outline for how to support your topic sentence in a logical manner. You can then link sentences by capitalizing on words or phrases to form bridges that carry the reader through the paragraph.⁵ These links are created through repetition of key words or through parallel grammatical forms.

4. Pump the brakes. No one likes an abrupt stop. When you’re winding down on a paragraph, you need to signal to the reader that you’re going to shift gears. The last sentence of a paragraph should serve as a natural transition to the next paragraph.⁶ Equally important is the transition line at the beginning of the next paragraph.

Regardless of where the transition occurs, the goal remains to help the reader follow your logic. A subsequent paragraph can extend or refute the argument that has been presented, or it can introduce an entirely new point. No matter what, you want the reader to be prepared for a change in focus and to stay with you through your transition to a new perspective or subtopic.

On the other hand, if the argument is exhausted—it stops. When your discussion is complete, the transition to the next paragraph is very different (eg, “In summary…”). This is an appropriate time to move to a new paragraph and new section.

Speaking of a new section, let’s switch our focus to form.

5. Take action. There are two types of “voice” in communication: active, in which the subject is taking some form of action (eg, You are reading this article), and passive, in which the action is performed upon the subject (eg, This article is being read by you). Active voice is preferred for several reasons—namely, clarity and space. An active sentence identifies who is doing what. The same conclusion may be reached through a passive sentence, with some effort on the reader’s part—but active sentences tend to be more concise. They also convey a sense of immediacy, hopefully drawing the reader into your article.

6. Punctuate like a pro. Punctuation is important! It provides structure, improving clarity and comprehension. Can you fathom the confusion that would occur if an author misused (or failed to use) appropriate punctuation?

Thankfully, rules regarding punctuation have not changed much over the past century. One notable exception is use of the serial (or “Oxford”) comma, which incites passionate debate among both amateur and professional linguists.⁷ (For the record, this publication uses the Oxford comma. Just ask the editors: Karen, Ann, and Amy.)

A full review of punctuation is beyond the scope of this article; however, be it known that the most problematic marks—the ones to double-check in your own writing—are the apostrophe (plural or singular possessive use), the semi-colon, the comma (or lack of), and quotation marks.⁸ To improve your punctuation, obtain a basic grammar handbook or search online.

7. Don’t volley with verbs. Verb tense should remain consistent throughout the paragraph.⁹ Paragraphs with multiple verb tenses bounce the reader’s mind back and forth. It’s like watching a ping pong match, but less enjoyable.

To check for consistency, print the manuscript and mix the order of the pages. Circle the verbs. Look at the circled words and assess the tense of each. Then, repair the damage.

It is easier to identify these types of problems with a manuscript when you’re reading the pages out of order. Editors will tell you that it is difficult to focus on particulars when you are distracted by the content of the paper. Out-of-order pages are harder to read for “sense,” so you can focus on tense, voice, and punctuation.

In conclusion, I hope I’ve helped you see that writing is a process—some say a craft—but it is one that anyone can tackle with the right mindset and preparation. Most authors have a key message; they may just need help expressing it. Starting with small elements, such as the paragraph, helps the author deliver the message clearly.

Unproven treatments for so-called chronic Lyme disease can cause serious, even fatal, complications, according to five case reports published in the Morbidity and Mortality Weekly Report.

“Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks,” the authors wrote.

Chronic Lyme disease is a nonspecific diagnosis that has no consistent definition. Some clinicians use this label for patients who have a variety of debilitating conditions such as fatigue, generalized pain, and neurologic symptoms, even in the absence of laboratory evidence of Borrelia burgdorferi infection, objective signs of infection, or a history of tick exposure. People who support this diagnosis mistakenly believe that B. burgdorferi can cause longstanding disabling symptoms even when standard testing for the organism is negative, when the truth is that tests for the organism become more sensitive the longer the infection persists, according to Natalie S. Marzec, MD, a resident in preventive medicine at the University of Colorado, Aurora, and her associates.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves,

Unproven treatments for so-called chronic Lyme disease can cause serious, even fatal, complications, according to five case reports published in the Morbidity and Mortality Weekly Report.

“Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks,” the authors wrote.

Chronic Lyme disease is a nonspecific diagnosis that has no consistent definition. Some clinicians use this label for patients who have a variety of debilitating conditions such as fatigue, generalized pain, and neurologic symptoms, even in the absence of laboratory evidence of Borrelia burgdorferi infection, objective signs of infection, or a history of tick exposure. People who support this diagnosis mistakenly believe that B. burgdorferi can cause longstanding disabling symptoms even when standard testing for the organism is negative, when the truth is that tests for the organism become more sensitive the longer the infection persists, according to Natalie S. Marzec, MD, a resident in preventive medicine at the University of Colorado, Aurora, and her associates.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves,

Unproven treatments for so-called chronic Lyme disease can cause serious, even fatal, complications, according to five case reports published in the Morbidity and Mortality Weekly Report.

“Patients, clinicians, and public health practitioners should be aware that treatments for chronic Lyme disease can carry serious risks,” the authors wrote.

Chronic Lyme disease is a nonspecific diagnosis that has no consistent definition. Some clinicians use this label for patients who have a variety of debilitating conditions such as fatigue, generalized pain, and neurologic symptoms, even in the absence of laboratory evidence of Borrelia burgdorferi infection, objective signs of infection, or a history of tick exposure. People who support this diagnosis mistakenly believe that B. burgdorferi can cause longstanding disabling symptoms even when standard testing for the organism is negative, when the truth is that tests for the organism become more sensitive the longer the infection persists, according to Natalie S. Marzec, MD, a resident in preventive medicine at the University of Colorado, Aurora, and her associates.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves,

MADRID  – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.

Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.

Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o

In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).

Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.

Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.

[email protected]
On Twitter @Alz_gal

MADRID  – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.

Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.

Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o

In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).

Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.

Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.

[email protected]
On Twitter @Alz_gal

MADRID  – To date, an adalimumab biosimilar has proven itself in a large, phase III trial of patients with psoriasis, including a subset with mild to moderate psoriatic arthritis (PsA).
The biosimilar, known as CHS-1420, cleared psoriatic plaques and improved health-related quality of life just as well as adalimumab after 12 weeks of treatment, Barbara Finck, MD, said at the European Congress of Rheumatology. It also suppressed high-sensitivity C-reactive protein (CRP) as well as the originator molecule, she said.

Dr. Finck, the chief medical officer of Coherus Biosciences, the developer of CHS-1420, reported results from the first 16-week phase of the 48-week study. Data are still to come on a 6-week period during which half those taking adalimumab switched to CHS-1420 in a blinded fashion, and 26 weeks of open-label CHS-1420 for all patients.
The study’s primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) Two additional endpoints were evaluated in patients with PsA: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and changes in CRP.

Dr. Finck bemoaned the lack of the clinical rheumatologic endpoint, tender and swollen joint count. “I advocated for this but was unable to convince our dermatology colleagues” to conduct this exam, she said. “I think we have a ways to go to educate our colleagues in this regard.”
The study comprised 545 patients with mild to moderate psoriasis; of these, 127 had PsA. They received subcutaneous injections of either CHS-1420 or adalimumab at identical doses (80 mg at week 1, followed by 40 mg every other week). They were a mean of 44 years o

In the entire study population, treatment with CHS-1420 and adalimumab followed almost identical response curves. By week 4, 22% of the CHS-1420 group and 20% of the adalimumab group had reached a PASI75 response. By week 8, those numbers were 57% and 61%, respectively, and by week 12, they were 69% and 72% – not significantly different.
Response was similar in the subgroup of PsA patients: By week 12, 82% of the CHS-1420 group and 77% of the adalimumab group had reached a PASI 75. PsA patients also responded equally well to both medications on the HAQ-DI by week 12. At baseline, the mean HAQ-DI was about 1 in each group. At 12 weeks, it was reduced by about half a point in both groups. High-sensitivity CRP decreased similarly in the CHS-1420 and adalimumab groups as well (reductions of 8.9 mg/L and 6.3 mg/L, respectively).

Adalimumab, a tumor necrosis factor blocker, is a highly immunogenic molecule, and as such, many patients developed antibodies to both it and to CHS-1420. By week 12, 84% of both treatment groups had developed anti-drug antibodies and 32%, neutralizing antibodies. Among those with PsA, 82% taking CHS-1420 and 88% of those taking adalimumab developed antidrug antibodies. Neutralizing antibodies developed in 33% and 30%, respectively. Neither of these differences was statistically significant.

Other adverse events were similar, Dr. Finck noted. These included nasopharyngitis (9% of both groups), upper respiratory tract infection (6%), injection site reaction (4%), headache (3%), and worsening of psoriasis (1% for CHS-1420, and 3% for adalimumab).
If the switching study data are similarly positive, Coherus expects to file a Biologics License Application with the Food and Drug Administration in early 2018, Dr. Finck said.

[email protected]
On Twitter @Alz_gal

Illustration: Kimberly Martens for OBG Management

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Etiology

Endometriomas are extensively described in the literature, and their origin is the subject of several theories. In 1921, Sampson noted luteal membrane and ovarian epithelial tissues within endometriomas and was the first to indicate that endometriomas may result from the invasion of functional cysts by endometrial tissue.^2,4,5 In 1979, Czernobilsky and Morris⁶ found endometrial and oviduct-like epithelium in ovarian endometriosis and concluded that ovarian tissue may be a common histologic precursor. Several other authors subsequently have reported finding different types of tissue within ovarian endometriomas, and not all of these chocolate cysts showed histologic evidence of endometriosis.^4,7,8

Read about the classification of endometriomas

Disease classification

Our classification system identifies 2 types of endometriomas on the basis of their etiologies and characteristics. Type I, which arise from endometrial tissue implanted on the ovarian surface, are also called true endometriomas. Invagination of cortex and subsequent hemorrhage from endometrial tissue result in cyst formation. Endometrial tissue (endometrial stroma and glands) is histologically present in all type I endometriomas.^1,4,9 These endometriomas usually are small (<5 cm in diameter) and have a densely adherent fibrous capsule.⁴ Often, there is no clear plane between cyst wall and ovarian stroma.³

Type II endometriomas arise from functional cysts involved in or invaded by cortical or pelvic side-wall endometrial implants or by type I endometriomas. Type II endometriomas are subclassified by the extent of endometrial implant involvement in the cyst wall. Type IIA endometriomas are hemorrhagic cysts with less than 10% of endometrial tissue within the cyst wall. Similar to the functional cysts from which they originate, type IIA endometriomas have a cyst wall that is separated easily from ovarian tissue during surgery.^4,7,9 Although type II endometriomas tend to be larger than their type I counterparts, in some cases they are identified at an early stage of 2 to 5 cm. Endometriomas larger than 5 cm are almost always type II.⁴

Type IIB and IIC endometriomas have endometrial implants and fibrosis within their cyst walls, with progressively more endometrial invasion in type IIC endometriomas (>50%) than in type IIB (10% to 50%). Consequently, type IIB cysts are relatively easy to dissect from ovarian tissue, except adjacent to an endometriotic area where the cyst densely adheres to the ovarian stroma. In type IIC, endometrial tissue more extensively penetrates the capsule, making dissection of diseased tissue from the ovarian stroma more difficult; in fact, separating type IIC cyst wall from ovarian stroma can be as challenging as excising a type I endometrioma.⁷ In most cases, a type IIC cyst is attached by adhesions and fibrosis to the pelvic side wall or uterus and ruptures during mobilization (TABLE).

Related article:
Imaging the endometrioma and mature cystic teratoma

Presentation and diagnosis

Almost all patients with an endometrioma concurrently have peritoneal endometriosis, which is characterized by dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, and, in some cases, gastrointestinal or genitourinary dysfunction.¹ Pelvic examination may reveal an adnexal mass that is an endometrioma, or an endometrioma may appear on imaging obtained in a pelvic pain or infertility work-up. Given its 73% sensitivity, 94% specificity, safety, and low cost, transvaginal ultrasonography is the preferred imaging modality for endometrioma.³ The characteristic ultrasonographic appearance is that of a round, homogeneous, fluid-filled mass with low-level echoes.¹ Magnetic resonance imaging is appropriate when a more sensitive imaging modality is indicated, as for a patient with risk factors for malignancy.^3,10–12

Read about the surgical management of endometriomas

Surgical management

Indications for surgical excision of endometriomas include pelvic pain, infertility, and prevention and diagnosis of malignancy. Endometriomas may be excised prior to use of assisted reproductive technology.^13–15 Medical therapy, such as oral contraceptives, can be used to reduce the size of endometriomas but does not improve fertility.³ Certain ovarian cancers are more common in women with endometriosis, and ovarian tumors are thought to develop in about 1% of ovarian endometriosis cases.^1,12 Therefore, endometrioma excision may reduce the risk of malignancy. As with other ovarian cysts, large endometriomas may be excised to reduce the risks of rupture and torsion.

Don't miss the video that accompanies this article!

---

To watch the authors perform laparoscopic excision of type I and type II endometriomas, click here

 

Approach

Laparoscopy is the preferred approach for endometrioma excision. Controversy exists regarding the ideal procedure: complete excision (with stripping of the cyst capsule) or drainage and ablation of the cyst wall. Compared with drainage and ablation, excision reduces recurrence of endometriomas; relieves dysmenorrhea, dyspareunia, pelvic pain, and other symptoms; and improves fertility.^13,16 The recurrence rate may be as low as 5.8% with complete excision but is 90% with simple transvaginal aspiration.^17,18 If not performed properly, however, cyst capsule stripping may damage nearby ovarian stroma and decrease the ovarian reserve.¹⁴ Some authors have advocated combining excision and ablation—performing cystectomy until there is no longer a clear plane between capsule and ovarian stroma and then ablating any remaining endometrial tissue.⁸

With type I and IIC endometriomas, we have seen the endometrial cyst wall infiltrating the ovarian stroma so deeply there is not always a definable plane. By contrast, type IIA and IIB endometriomas typically have a plane between the cyst wall and the ovarian cortex. In type II endometriomas, endometrial implants on the ovarian cortex infiltrate the plane of the cyst wall such that the juxtaposing lipomatous follicular cyst detaches with minimal intraoperative traction. Portions of type II endometriomas containing fibrosis and adhesions may become more difficult to peel off the cyst wall. For most endometriomas, at least 1 spot is difficult to peel off the ovary, and extra care must be taken at the hilum of ovary to avoid excising healthy ovarian cortex.^4,5,7,8

Our surgical approach accounts for the described variations in type I and II endometriomas. Endometrial contents often spill as the endometrioma is dissected off neighboring structures. When possible, endometriomas should be aspirated and irrigated prior to cystectomy to avoid seeding the pelvis and abdomen with spilled endometriotic contents. We use hydrodissection, the injection of dilute vasopressin with a laparoscopic needle, to create a plane between cyst wall and ovarian stroma and strip the cyst capsule with laparoscopic graspers. Type I endometriomas adhere densely to the ovary. Given the presence of fibrosis and adhesions, the cyst is excised in a piecemeal fashion. Care is taken to remove any endometrial implants from the ovary while preserving as much of the ovarian tissue as possible.¹

Type II endometriomas are larger cysts originating from the invasion of endometrial implants or type I endometrioma into functional cysts. The difficulty of capsule excision varies according to the extent of endometrial invasion. Type IIA endometriomas contain less than 10% endometrial tissue within the cyst capsule. Thus, the standard ovarian cystectomy stripping technique is successful in removing more than 90% of the cyst capsule. Special care is taken in stripping the residual small portion that involves the endometrial glands and stroma and adheres densely to the ovary.

The larger proportion of endometrial tissue present in type IIB and IIC endometriomas degrades the plane between the cyst capsule and the ovarian stroma, making excision more difficult. Similar to the type I excision, a piecemeal approach is often necessary. If complete stripping of the cyst capsule would result in extensive loss of healthy ovarian tissue, then electrocautery, plasma energy, or laser ablation can be selectively used to destroy focal areas of endometrial invasion. Complete ablation may be difficult, as the endometrioma wall can be up to 5 mm thick.¹⁹ For these thick-walled endometriomas, we recommend excision (vs ablation), which lowers the risk of endometrioma recurrence.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options
 

Conclusion

Endometriomas, common adnexal masses in women affected by endometriosis, may exacerbate pelvic pain and impair fertility. Gynecologists should be prepared to excise endometriomas completely and exercise care in preserving as much of the ovarian stroma as possible. We classify endometriomas into 2 types: type I, which develop from invagination of endometrial implants in the ovarian cortex, and type II, which stem from invasion of functional cysts by endometrial implants or type I endometrioma. This distinction guides surgical management. We hope this article and its accompanying video will be helpful in guiding laparoscopic excision of type I and II endometriomas.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Etiology

Endometriomas are extensively described in the literature, and their origin is the subject of several theories. In 1921, Sampson noted luteal membrane and ovarian epithelial tissues within endometriomas and was the first to indicate that endometriomas may result from the invasion of functional cysts by endometrial tissue.^2,4,5 In 1979, Czernobilsky and Morris⁶ found endometrial and oviduct-like epithelium in ovarian endometriosis and concluded that ovarian tissue may be a common histologic precursor. Several other authors subsequently have reported finding different types of tissue within ovarian endometriomas, and not all of these chocolate cysts showed histologic evidence of endometriosis.^4,7,8

Read about the classification of endometriomas

Disease classification

Our classification system identifies 2 types of endometriomas on the basis of their etiologies and characteristics. Type I, which arise from endometrial tissue implanted on the ovarian surface, are also called true endometriomas. Invagination of cortex and subsequent hemorrhage from endometrial tissue result in cyst formation. Endometrial tissue (endometrial stroma and glands) is histologically present in all type I endometriomas.^1,4,9 These endometriomas usually are small (<5 cm in diameter) and have a densely adherent fibrous capsule.⁴ Often, there is no clear plane between cyst wall and ovarian stroma.³

Type II endometriomas arise from functional cysts involved in or invaded by cortical or pelvic side-wall endometrial implants or by type I endometriomas. Type II endometriomas are subclassified by the extent of endometrial implant involvement in the cyst wall. Type IIA endometriomas are hemorrhagic cysts with less than 10% of endometrial tissue within the cyst wall. Similar to the functional cysts from which they originate, type IIA endometriomas have a cyst wall that is separated easily from ovarian tissue during surgery.^4,7,9 Although type II endometriomas tend to be larger than their type I counterparts, in some cases they are identified at an early stage of 2 to 5 cm. Endometriomas larger than 5 cm are almost always type II.⁴

Type IIB and IIC endometriomas have endometrial implants and fibrosis within their cyst walls, with progressively more endometrial invasion in type IIC endometriomas (>50%) than in type IIB (10% to 50%). Consequently, type IIB cysts are relatively easy to dissect from ovarian tissue, except adjacent to an endometriotic area where the cyst densely adheres to the ovarian stroma. In type IIC, endometrial tissue more extensively penetrates the capsule, making dissection of diseased tissue from the ovarian stroma more difficult; in fact, separating type IIC cyst wall from ovarian stroma can be as challenging as excising a type I endometrioma.⁷ In most cases, a type IIC cyst is attached by adhesions and fibrosis to the pelvic side wall or uterus and ruptures during mobilization (TABLE).

Related article:
Imaging the endometrioma and mature cystic teratoma

Presentation and diagnosis

Almost all patients with an endometrioma concurrently have peritoneal endometriosis, which is characterized by dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, and, in some cases, gastrointestinal or genitourinary dysfunction.¹ Pelvic examination may reveal an adnexal mass that is an endometrioma, or an endometrioma may appear on imaging obtained in a pelvic pain or infertility work-up. Given its 73% sensitivity, 94% specificity, safety, and low cost, transvaginal ultrasonography is the preferred imaging modality for endometrioma.³ The characteristic ultrasonographic appearance is that of a round, homogeneous, fluid-filled mass with low-level echoes.¹ Magnetic resonance imaging is appropriate when a more sensitive imaging modality is indicated, as for a patient with risk factors for malignancy.^3,10–12

Read about the surgical management of endometriomas

Surgical management

Indications for surgical excision of endometriomas include pelvic pain, infertility, and prevention and diagnosis of malignancy. Endometriomas may be excised prior to use of assisted reproductive technology.^13–15 Medical therapy, such as oral contraceptives, can be used to reduce the size of endometriomas but does not improve fertility.³ Certain ovarian cancers are more common in women with endometriosis, and ovarian tumors are thought to develop in about 1% of ovarian endometriosis cases.^1,12 Therefore, endometrioma excision may reduce the risk of malignancy. As with other ovarian cysts, large endometriomas may be excised to reduce the risks of rupture and torsion.

Don't miss the video that accompanies this article!

---

To watch the authors perform laparoscopic excision of type I and type II endometriomas, click here

 

Approach

Laparoscopy is the preferred approach for endometrioma excision. Controversy exists regarding the ideal procedure: complete excision (with stripping of the cyst capsule) or drainage and ablation of the cyst wall. Compared with drainage and ablation, excision reduces recurrence of endometriomas; relieves dysmenorrhea, dyspareunia, pelvic pain, and other symptoms; and improves fertility.^13,16 The recurrence rate may be as low as 5.8% with complete excision but is 90% with simple transvaginal aspiration.^17,18 If not performed properly, however, cyst capsule stripping may damage nearby ovarian stroma and decrease the ovarian reserve.¹⁴ Some authors have advocated combining excision and ablation—performing cystectomy until there is no longer a clear plane between capsule and ovarian stroma and then ablating any remaining endometrial tissue.⁸

With type I and IIC endometriomas, we have seen the endometrial cyst wall infiltrating the ovarian stroma so deeply there is not always a definable plane. By contrast, type IIA and IIB endometriomas typically have a plane between the cyst wall and the ovarian cortex. In type II endometriomas, endometrial implants on the ovarian cortex infiltrate the plane of the cyst wall such that the juxtaposing lipomatous follicular cyst detaches with minimal intraoperative traction. Portions of type II endometriomas containing fibrosis and adhesions may become more difficult to peel off the cyst wall. For most endometriomas, at least 1 spot is difficult to peel off the ovary, and extra care must be taken at the hilum of ovary to avoid excising healthy ovarian cortex.^4,5,7,8

Our surgical approach accounts for the described variations in type I and II endometriomas. Endometrial contents often spill as the endometrioma is dissected off neighboring structures. When possible, endometriomas should be aspirated and irrigated prior to cystectomy to avoid seeding the pelvis and abdomen with spilled endometriotic contents. We use hydrodissection, the injection of dilute vasopressin with a laparoscopic needle, to create a plane between cyst wall and ovarian stroma and strip the cyst capsule with laparoscopic graspers. Type I endometriomas adhere densely to the ovary. Given the presence of fibrosis and adhesions, the cyst is excised in a piecemeal fashion. Care is taken to remove any endometrial implants from the ovary while preserving as much of the ovarian tissue as possible.¹

Type II endometriomas are larger cysts originating from the invasion of endometrial implants or type I endometrioma into functional cysts. The difficulty of capsule excision varies according to the extent of endometrial invasion. Type IIA endometriomas contain less than 10% endometrial tissue within the cyst capsule. Thus, the standard ovarian cystectomy stripping technique is successful in removing more than 90% of the cyst capsule. Special care is taken in stripping the residual small portion that involves the endometrial glands and stroma and adheres densely to the ovary.

The larger proportion of endometrial tissue present in type IIB and IIC endometriomas degrades the plane between the cyst capsule and the ovarian stroma, making excision more difficult. Similar to the type I excision, a piecemeal approach is often necessary. If complete stripping of the cyst capsule would result in extensive loss of healthy ovarian tissue, then electrocautery, plasma energy, or laser ablation can be selectively used to destroy focal areas of endometrial invasion. Complete ablation may be difficult, as the endometrioma wall can be up to 5 mm thick.¹⁹ For these thick-walled endometriomas, we recommend excision (vs ablation), which lowers the risk of endometrioma recurrence.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options
 

Conclusion

Endometriomas, common adnexal masses in women affected by endometriosis, may exacerbate pelvic pain and impair fertility. Gynecologists should be prepared to excise endometriomas completely and exercise care in preserving as much of the ovarian stroma as possible. We classify endometriomas into 2 types: type I, which develop from invagination of endometrial implants in the ovarian cortex, and type II, which stem from invasion of functional cysts by endometrial implants or type I endometrioma. This distinction guides surgical management. We hope this article and its accompanying video will be helpful in guiding laparoscopic excision of type I and II endometriomas.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Related article:
Endometriosis: Expert answers to 7 crucial questions on diagnosis

Etiology

Endometriomas are extensively described in the literature, and their origin is the subject of several theories. In 1921, Sampson noted luteal membrane and ovarian epithelial tissues within endometriomas and was the first to indicate that endometriomas may result from the invasion of functional cysts by endometrial tissue.^2,4,5 In 1979, Czernobilsky and Morris⁶ found endometrial and oviduct-like epithelium in ovarian endometriosis and concluded that ovarian tissue may be a common histologic precursor. Several other authors subsequently have reported finding different types of tissue within ovarian endometriomas, and not all of these chocolate cysts showed histologic evidence of endometriosis.^4,7,8

Read about the classification of endometriomas

Disease classification

Our classification system identifies 2 types of endometriomas on the basis of their etiologies and characteristics. Type I, which arise from endometrial tissue implanted on the ovarian surface, are also called true endometriomas. Invagination of cortex and subsequent hemorrhage from endometrial tissue result in cyst formation. Endometrial tissue (endometrial stroma and glands) is histologically present in all type I endometriomas.^1,4,9 These endometriomas usually are small (<5 cm in diameter) and have a densely adherent fibrous capsule.⁴ Often, there is no clear plane between cyst wall and ovarian stroma.³

Type II endometriomas arise from functional cysts involved in or invaded by cortical or pelvic side-wall endometrial implants or by type I endometriomas. Type II endometriomas are subclassified by the extent of endometrial implant involvement in the cyst wall. Type IIA endometriomas are hemorrhagic cysts with less than 10% of endometrial tissue within the cyst wall. Similar to the functional cysts from which they originate, type IIA endometriomas have a cyst wall that is separated easily from ovarian tissue during surgery.^4,7,9 Although type II endometriomas tend to be larger than their type I counterparts, in some cases they are identified at an early stage of 2 to 5 cm. Endometriomas larger than 5 cm are almost always type II.⁴

Type IIB and IIC endometriomas have endometrial implants and fibrosis within their cyst walls, with progressively more endometrial invasion in type IIC endometriomas (>50%) than in type IIB (10% to 50%). Consequently, type IIB cysts are relatively easy to dissect from ovarian tissue, except adjacent to an endometriotic area where the cyst densely adheres to the ovarian stroma. In type IIC, endometrial tissue more extensively penetrates the capsule, making dissection of diseased tissue from the ovarian stroma more difficult; in fact, separating type IIC cyst wall from ovarian stroma can be as challenging as excising a type I endometrioma.⁷ In most cases, a type IIC cyst is attached by adhesions and fibrosis to the pelvic side wall or uterus and ruptures during mobilization (TABLE).

Related article:
Imaging the endometrioma and mature cystic teratoma

Presentation and diagnosis

Almost all patients with an endometrioma concurrently have peritoneal endometriosis, which is characterized by dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, and, in some cases, gastrointestinal or genitourinary dysfunction.¹ Pelvic examination may reveal an adnexal mass that is an endometrioma, or an endometrioma may appear on imaging obtained in a pelvic pain or infertility work-up. Given its 73% sensitivity, 94% specificity, safety, and low cost, transvaginal ultrasonography is the preferred imaging modality for endometrioma.³ The characteristic ultrasonographic appearance is that of a round, homogeneous, fluid-filled mass with low-level echoes.¹ Magnetic resonance imaging is appropriate when a more sensitive imaging modality is indicated, as for a patient with risk factors for malignancy.^3,10–12

Read about the surgical management of endometriomas

Surgical management

Indications for surgical excision of endometriomas include pelvic pain, infertility, and prevention and diagnosis of malignancy. Endometriomas may be excised prior to use of assisted reproductive technology.^13–15 Medical therapy, such as oral contraceptives, can be used to reduce the size of endometriomas but does not improve fertility.³ Certain ovarian cancers are more common in women with endometriosis, and ovarian tumors are thought to develop in about 1% of ovarian endometriosis cases.^1,12 Therefore, endometrioma excision may reduce the risk of malignancy. As with other ovarian cysts, large endometriomas may be excised to reduce the risks of rupture and torsion.

Don't miss the video that accompanies this article!

---

To watch the authors perform laparoscopic excision of type I and type II endometriomas, click here

 

Approach

Laparoscopy is the preferred approach for endometrioma excision. Controversy exists regarding the ideal procedure: complete excision (with stripping of the cyst capsule) or drainage and ablation of the cyst wall. Compared with drainage and ablation, excision reduces recurrence of endometriomas; relieves dysmenorrhea, dyspareunia, pelvic pain, and other symptoms; and improves fertility.^13,16 The recurrence rate may be as low as 5.8% with complete excision but is 90% with simple transvaginal aspiration.^17,18 If not performed properly, however, cyst capsule stripping may damage nearby ovarian stroma and decrease the ovarian reserve.¹⁴ Some authors have advocated combining excision and ablation—performing cystectomy until there is no longer a clear plane between capsule and ovarian stroma and then ablating any remaining endometrial tissue.⁸

With type I and IIC endometriomas, we have seen the endometrial cyst wall infiltrating the ovarian stroma so deeply there is not always a definable plane. By contrast, type IIA and IIB endometriomas typically have a plane between the cyst wall and the ovarian cortex. In type II endometriomas, endometrial implants on the ovarian cortex infiltrate the plane of the cyst wall such that the juxtaposing lipomatous follicular cyst detaches with minimal intraoperative traction. Portions of type II endometriomas containing fibrosis and adhesions may become more difficult to peel off the cyst wall. For most endometriomas, at least 1 spot is difficult to peel off the ovary, and extra care must be taken at the hilum of ovary to avoid excising healthy ovarian cortex.^4,5,7,8

Our surgical approach accounts for the described variations in type I and II endometriomas. Endometrial contents often spill as the endometrioma is dissected off neighboring structures. When possible, endometriomas should be aspirated and irrigated prior to cystectomy to avoid seeding the pelvis and abdomen with spilled endometriotic contents. We use hydrodissection, the injection of dilute vasopressin with a laparoscopic needle, to create a plane between cyst wall and ovarian stroma and strip the cyst capsule with laparoscopic graspers. Type I endometriomas adhere densely to the ovary. Given the presence of fibrosis and adhesions, the cyst is excised in a piecemeal fashion. Care is taken to remove any endometrial implants from the ovary while preserving as much of the ovarian tissue as possible.¹

Type II endometriomas are larger cysts originating from the invasion of endometrial implants or type I endometrioma into functional cysts. The difficulty of capsule excision varies according to the extent of endometrial invasion. Type IIA endometriomas contain less than 10% endometrial tissue within the cyst capsule. Thus, the standard ovarian cystectomy stripping technique is successful in removing more than 90% of the cyst capsule. Special care is taken in stripping the residual small portion that involves the endometrial glands and stroma and adheres densely to the ovary.

The larger proportion of endometrial tissue present in type IIB and IIC endometriomas degrades the plane between the cyst capsule and the ovarian stroma, making excision more difficult. Similar to the type I excision, a piecemeal approach is often necessary. If complete stripping of the cyst capsule would result in extensive loss of healthy ovarian tissue, then electrocautery, plasma energy, or laser ablation can be selectively used to destroy focal areas of endometrial invasion. Complete ablation may be difficult, as the endometrioma wall can be up to 5 mm thick.¹⁹ For these thick-walled endometriomas, we recommend excision (vs ablation), which lowers the risk of endometrioma recurrence.

Related article:
Endometriosis and pain: Expert answers to 6 questions targeting your management options
 

Conclusion

Endometriomas, common adnexal masses in women affected by endometriosis, may exacerbate pelvic pain and impair fertility. Gynecologists should be prepared to excise endometriomas completely and exercise care in preserving as much of the ovarian stroma as possible. We classify endometriomas into 2 types: type I, which develop from invagination of endometrial implants in the ovarian cortex, and type II, which stem from invasion of functional cysts by endometrial implants or type I endometrioma. This distinction guides surgical management. We hope this article and its accompanying video will be helpful in guiding laparoscopic excision of type I and II endometriomas.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

If you are a busy primary care physician, wouldn’t you like to get some quick confirmation that your patient with a fever and runny nose has a viral upper respiratory infection? If there were a test or a simple physical finding that could give you the answer while the patient was still in the office, you could dispense a quick dose of reassurance and send him or her on their way. It would probably help you inch a bit closer to relieving the congestion in your waiting room.

I am sure most of you realize that relying on the patient’s temperature or the color of his or her nasal mucus is not going to give you that reliable and swift answer you would like. There have been rapid diagnostic tests for influenza on the market for several years, but I have not been aware of a similar test for rhinovirus. But I recently came across a study that offers some hope that such a test might become a reality in the future (EBioMedicine. 2017 Mar;17:172-81). In the study, researchers at Duke University and elsewhere identified a group of proteins in mucus that can confirm – with 86% accuracy – that the patient is infected with a cold or flu virus. They anticipate that this discovery could be adapted into a rapid test that could be performed in the doctor’s office.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are a busy primary care physician, wouldn’t you like to get some quick confirmation that your patient with a fever and runny nose has a viral upper respiratory infection? If there were a test or a simple physical finding that could give you the answer while the patient was still in the office, you could dispense a quick dose of reassurance and send him or her on their way. It would probably help you inch a bit closer to relieving the congestion in your waiting room.

I am sure most of you realize that relying on the patient’s temperature or the color of his or her nasal mucus is not going to give you that reliable and swift answer you would like. There have been rapid diagnostic tests for influenza on the market for several years, but I have not been aware of a similar test for rhinovirus. But I recently came across a study that offers some hope that such a test might become a reality in the future (EBioMedicine. 2017 Mar;17:172-81). In the study, researchers at Duke University and elsewhere identified a group of proteins in mucus that can confirm – with 86% accuracy – that the patient is infected with a cold or flu virus. They anticipate that this discovery could be adapted into a rapid test that could be performed in the doctor’s office.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you are a busy primary care physician, wouldn’t you like to get some quick confirmation that your patient with a fever and runny nose has a viral upper respiratory infection? If there were a test or a simple physical finding that could give you the answer while the patient was still in the office, you could dispense a quick dose of reassurance and send him or her on their way. It would probably help you inch a bit closer to relieving the congestion in your waiting room.

I am sure most of you realize that relying on the patient’s temperature or the color of his or her nasal mucus is not going to give you that reliable and swift answer you would like. There have been rapid diagnostic tests for influenza on the market for several years, but I have not been aware of a similar test for rhinovirus. But I recently came across a study that offers some hope that such a test might become a reality in the future (EBioMedicine. 2017 Mar;17:172-81). In the study, researchers at Duke University and elsewhere identified a group of proteins in mucus that can confirm – with 86% accuracy – that the patient is infected with a cold or flu virus. They anticipate that this discovery could be adapted into a rapid test that could be performed in the doctor’s office.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bacterial vaginosis (BV) is caused by a complex change in vaginal bacterial flora, with a reduction in lactobacilli (which help maintain an acidic environment) and an increase in anaerobic gram-negative organisms including Gardnerella vaginalis species and Bacteroides, Prevotella, and Mobiluncus genera. Infection with G vaginalis is thought to trigger a cascade of changes in vaginal flora that leads to BV.¹

Photo: CDC/ M. Rein

BV is present in 30% to 50% of sexually active women, and of these women 50% to 75% have an abnormal vaginal discharge, which is gray, thin, and homogeneous and may have a fishy odor.² In addition to causing an abnormal vaginal discharge, BV is a cause of postpartum fever, posthysterectomy vaginal cuff cellulitis, and postabortion infection, and it increases the risk of acquiring HIV, herpes simplex type 2, gonorrhea, chlamydia, and trichomoniasis infection.³

When using microscopy and the Amsel criteria, the diagnosis of BV is made when at least 3 of the following 4 criteria are present:  

1. homogeneous, thin, gray discharge  
2. vaginal pH >4.5  
3. positive whiff-amine test when applying a drop of 10% KOH to a sample of the vaginal discharge  
4. clue cells detected with microscopy on a saline wet mount.  

If microscopy is not available, the Affirm VPIII test (BD Diagnostic Systems, Franklin Lakes, New Jersey) for DNA sequences of G vaginalis has high sensitivity and specificity.⁴ The OSOM BVBlue test (Sekisui Diagnostics, Lexington, Massachusetts), a Clinical Laboratory Improvement Amendments-waived point of service test, measures vaginal sialidase, which is produced by Gardnerella and other pathogens associated with BV.⁵ BV may be detected in routine cervical cytology testing and, if the patient is symptomatic, treatment is recommended.

Initial treatment of BV. The Centers for Disease Control and Prevention (CDC) has recommended 3 treatment regimens for BV and 4 alternative treatment options (TABLE).⁶ In addition to antimicrobial treatment, the CDC recommends that women with BV use condoms with sexual intercourse. The CDC also advises that clinicians should con-sider testing women with BV for HIV and other sexually transmitted infections.

Related article:
Successful treatment of chronic vaginitis

Treatment of recurrent BV

A major problem with BV is that, although initial treatment is successful in about 80% of cases, up to 50% of women will have a recurrence of BV within 12 months of initial treatment.² Preliminary studies suggest that for women with 3 or more episodes of BV, the regimens below may be effective.  

Regimen 1
Following the completion of a CDC-recommended treatment regimen (see TABLE), prescribe metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 6 months.⁷

In a prospective randomized trial examining this regimen, following initial treatment with a 10-day metronidazole vaginal gel regimen 112 women were randomly assigned to chronic suppressive therapy with metronidazole vaginal gel 0.75%, one full applicator, twice weekly for 16 weeks or a placebo. During the treatment period, recurrent BV was diagnosed in 26% of the women taking metronidazole gel and 59% of the women taking placebo.⁷ This regimen may be complicated by secondary vaginal candidiasis, which may be treated with a vaginal or oral antifungal agent. 

Regimen 2
Initiate a 21-day course of vaginal boric acid capsules 600 mg once daily at bedtime and simultaneously prescribe a standard CDC treatment regimen (see TABLE). At the completion of the vaginal boric acid treatment initiate metronidazole vaginal gel 0.75% twice weekly for 6 months.⁸

NOTE: Boric acid can cause death if consumed orally.⁹ Boric acid capsules should be stored securely to ensure that they are not accidentally taken orally. Boric acid poisoning may present with vomiting, fever, skin rash, neutropenia, thrombocytopenia, metabolic acidosis, and renal failure.¹⁰ Boric acid should not be used by pregnant women because it is a teratogen.¹¹

The bacterial organisms responsible for BV reside in a self-produced matrix, referred to as a biofilm, that protect the organisms from antimicrobial agents.¹² Boric acid may prevent the formation of a biofilm and increase the effectiveness of anti-microbial treatment.

Regimen 3
Following the completion of a standard treatment regimen (see TABLE), prescribe oral metronidazole 2 g and fluconazole 150 mg administered once every month.¹³

In a randomized clinical trial, 310 female sex workers were randomly assigned to monthly treatment with oral metronidazole 2 g plus fluconazole 150 mg or placebo for up to 12 months.¹³ In the treatment and placebo groups episodes of BV were 199 and 326 per 100 person-years, respectively (hazard ratio, 0.55; 95% confidence interval, 0.49-0.63; P<.001). In Canada, a vaginal ovule containing both a high dose of metronidazole (500 mg) and nystatin (10,000 IU) is available and could be used intermittently to prevent recurrence.¹⁴

Treatment of partners

The CDC does not recommend treatment of the partners of women with BV because there are no definitive data to support such a recommendation. However, the 6 published clinical trials testing the utility of treating sex partners of women with BV have significant methodologic flaws, including underpowered studies and suboptimal antibiotic treatment regimens.¹⁵ Hence, whether partners should be treated remains an open question. Many experts believe that, in most cases, BV is a sexually transmitted disease.^16,17 For women who have sex with women, the rate of BV concordance among partners is high. If one woman has diagnosed BV and symptoms are present in her partner, treatment of the partner is reasonable. For women with BV who have sex with men, sexual intercourse influences disease activity, and consistent use of condoms may reduce the rate of recurrence.¹⁸ Male circumcision may reduce the risk of BV in female partners.¹⁹

Related article:
Bacterial vaginosis: Meet patients' needs with effective diagnosis and treatment

Over-the-counter treatments

In women with BV it is thought that the vaginal administration of lactic acid can help restore the normal acidic pH of the vagina, encourage the growth of lactobacilli, and suppress the growth of the bacteria that cause BV.²⁰ Many products containing lactic acid in a formulation for vaginal use are available (among them Luvena and Gynofit gel).

Lactobacilli play an important role in maintaining vaginal health. Lactobacillus rhamnosus and Lactobacillus reuteri are available for purchase as supplements for oral administration. It is thought that oral administration of lactobacilli can help improve the vaginal microbiome. In one clinical trial, 125 women with BV were randomly assigned to receive the combination of 1 week of metronidazole plus oral Lactobacillus twice daily for 30 days or metronidazole plus placebo.²¹ Resolution of symptoms was reported as 88% and 40% in the metronidazole-lactobacilli and metronidazole-placebo groups, respectively.²¹ By contrast, one systematic review of probiotic treatment of BV concluded that there is insufficient evidence to recommend for or against probiotic treatment of BV.²² Patients with recurrent BV commonly report that they believe a probiotic was helpful in resolving their symptoms.

On the horizon

In one trial, a single 2-g oral dose of secnidazole was as effective as a 7-day course of oral metronidazole 500 mg twice daily.²³ In a small dose-finding study, a single dose of either secnidazole 1 g or 2 g was equally effective in treating BV.²⁴ An effective single-dose treatment of BV would likely improve patient adherence with therapy. Symbiomix is preparing for FDA review of this medication (secnidazole, Solosec) for use in the United States.

BV is a prevalent problem and often adversely impacts a woman's quality of life and love relationships. BV recurrence is very common. Many women report that their BV was resistant to intermittet treatment and recurred, repetitively  over many years. The 3 treatment options presented in this editorial may help to suppress the recurrence rate and improve symptoms.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.

After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.

Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.

In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.

BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.

After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.

Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.

In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.

BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.

After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.

Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.

In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.

SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.

“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.

The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.

SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.

“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.

The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.

SAN DIEGO – Based on their analysis of a cohort of more than half a million people, Swedish researchers now believe that mildly elevated fasting plasma glucose and triglyceride levels could indicate an increased risk for type 2 diabetes a quarter-century before diagnosis.

“Previous studies have shown that risk factors for type 2 diabetes, including obesity and elevated fasting glucose, may be present up to 10 years before disease onset. Our study extends this period to more than 20 years before diagnosis,” said the study’s lead author Håkan Malmström, PhD, an epidemiologist with the Karolinska Institute, Stockholm. “Even small elevations in subjects over time early in life may be important to recognize, in particular for people who are overweight or obese.” The study findings were presented in an oral presentation at the scientific sessions of the American Diabetes Association.

The researchers identified 47,997 new type 2 diabetes cases in a Swedish cohort of 537,119 people tracked from 1985-2012. For each case, they compared risk factors from clinical examinations performed from 1985-1996 with those of five matched controls.