Treatment sequence network meta-analysis in Crohn’s disease: a methodological case study

Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.

Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.

Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.

Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.     

Relative Accuracy of Fine-Needle Aspiration and Frozen Section in the Diagnosis of Well-Differentiated Thyroid Cancer

The need for and extent of thyroid surgery for a thyroid nodule is usually primarily based on fine-needle aspiration (FNA) and frozen section diagnosis. The relative role of these modalities in 66 patients who had undergone FNA and subsequent thyroidectomy with frozen section was investigated. Cases that demonstrated discordance between FNA and frozen section (n = 22; 33%) were identified, and all slides were re-reviewed by a cytopathologist using current established cytologic criteria. A change in diagnosis was made in 13 cases with an increase in accuracy of FNA from 71% to 88%. The accuracy of frozen section (92%) did not change appreciably with re-review (94%). The accuracy of FNA and frozen section combined was found to be 98%. The rate of discordance decreased from 33% to 13% with re-review. When strict histologic and cytologic criteria are applied, FNA and frozen section are accurate and complementary methods that help in determining the operative management of thyroid masses. However, when FNA yields a diagnosis of “follicular neoplasm,” frozen section is unlikely to change this diagnosis.     

Assessing decision-making capacity in elderly patients: the gynecologist's role

To obtain informed consent, a physician must be able to assess a patient's capacity to consent to treatment. She must be able to understand the information, appreciate how it applies to her situation, rationally process it to make reasonable choices, and express herself. Medicine and law no longer view capacity as dichotomous (fully capable or absolutely not). Patients may be able to make some choices but not others. There is a legal point at which decision-making capacity should be transferred from a patient to a surrogate, but the patient need not be henceforth excluded from the decision-making process.     

Management of cervical intraepithelial neoplasia 2 in adolescent and young women

STUDY OBJECTIVE: To evaluate regression rates among adolescents (aged < or =21) with cervical intraepithelial neoplasia (CIN) 2 managed expectantly and to determine factors associated with disease regression. DESIGN: Cohort study using a colposcopic database of 2,996 women seen between August 1999 and November 2005. SETTING: Colposcopy clinic in urban, tertiary care medical center. PARTICIPANTS: Adolescents with CIN 2. Routine management consisted of two options: immediate treatment or repeat colposcopic evaluation in 6 months. MAIN OUTCOME MEASURES: For those managed conservatively, regression was defined either as a subsequent normal colposcopy and/or biopsy and at least 2 smears read as negative for epithelial abnormality or at least 3 consecutive negative smears if repeat colposcopy was not performed. Demographic information, including age, was assessed to determine possible associations with disease regression. RESULTS: Of the 93 adolescents, 53 (57%) elected to undergo immediate treatment with a diagnostic excisional procedure, and 40 (43%) chose management with colposcopic follow-up. Of those treated, high-grade disease (CIN 2+) was found in 40 (75%). Of the 36 young women followed conservatively (4 were lost to follow-up), regression after a median follow-up time of 378 days was documented in 14 (39%). Of the 22 adolescents not fulfilling our criteria for regression, only 3 had evidence of CIN 2 or worse during follow-up. The remaining 19 had either CIN 1 or mildly abnormal cytologic results. Kaplan-Meier survival estimates indicated younger age (< or =16 years) tended to be associated with decreased time to regression. CONCLUSION: Based on significant regression of CIN 2 among adolescent women, primary management in this population should consist of cytologic and colposcopic follow-up.     

The Effect of Integrating Family Planning with a Maternal and Newborn Health Program on Postpartum Contraceptive Use and Optimal Birth Spacing in Rural Bangladesh

Meeting postpartum contraceptive need remains a major challenge in developing countries, where the majority of women deliver at home. Using a quasi‐experimental trial design, we examine the effect of integrating family planning (FP) with a community‐based maternal and newborn health (MNH) program on improving postpartum contraceptive use and reducing short birth intervals <24 months. In this two‐arm trial, community health workers (CHWs) provided integrated FP counseling and services during home visits along with their outreach MNH activities in the intervention arm, but provided only MNH services in the control arm. The contraceptive prevalence rate (CPR) in the intervention arm was 15 percent higher than in the control arm at 12 months, and the difference in CPRs remained statistically significant throughout the 24 months of observation. The short birth interval of less than 24 months was significantly lower in the intervention arm. The study demonstrates that it is feasible and effective to integrate FP services into a community‐based MNH care program for improving postpartum contraceptive use and lengthening birth intervals.     

Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer—A Literature Review

Background: Approximately 75% of breast cancer (BC) is associated with luminal differentiation expressing endocrine receptors (ER). For ER+ HER2− tumors, adjuvant endocrine therapy (ET) is the cornerstone treatment. Although relapse events steadily continue, the ET benefits translate to dramatically lengthen life expectancy with bearable side-effects. This review of ER+ HER2− female BC outlines suitable adjuvant treatment strategies to help guide clinical decision making around appropriate therapy. Methods: A literature search was conducted in Embase, Medline, and the Cochrane Libraries, using ER+ HER−, ET BC keywords. Results: In low-risk patients: five years of ET is the standard option. While Tamoxifen remains the preferred selection for premenopausal women, AI is the choice for postmenopausal patients. In the high-risk category: ET plus/minus OFS with two years of Abemaciclib is recommended. Although extended ET for a total of ten years is an alternative, the optimal AI duration is undetermined; nevertheless an additional two to three years beyond the initial five years may be sufficient. In this postmenopausal group, bisphosphonate is endorsed. Conclusions: Classifying the risk category assists in deciding the treatment route and its optimal duration. Tailoring the breadth of ET hinges on a wide array of factors to be appraised for each individualized case, including weighing its benefits and harms.     

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes,Australia

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.     

Assessment of left ventricular mechanical dyssynchrony by phase analysis of ECG-gated SPECT myocardial perfusion imaging

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset-of-mechanical contraction phase. Once the onset-of-mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.     

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (−90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (−45%), and other organs saw similar decreases: lung (−70%), heart (−43%), and liver (−37%). Deceased donors recovered dropped from 260 to 163 (−45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (−67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.     

Summer Research Training for Medical Students: Impact on Research Self‐Efficacy

There is a well‐documented shortage of physician researchers, and numerous training programs have been launched to facilitate development of new physician scientists. Short‐term research training programs are the most practical form of research exposure for most medical students, and the summer between their first and second years of medical school is generally the longest period they can devote solely to research. The goal of short‐term training programs is to whet the students’ appetite for research and spark their interest in the field. Relatively little research has been done to test the effectiveness of short‐term research training programs. In an effort to examine short‐term effects of three different NIH‐funded summer research training programs for medical students, we assessed the trainees’ (N = 75) research self‐efficacy prior to and after the programs using an 11‐item scale. These hands‐on training programs combined experiential, didactic, and mentoring elements. The students demonstrated a significant increase in their self‐efficacy for research. Trainees’ gender, ranking of their school, type of research, and specific content of research project did not predict improvement. Effect sizes for different types of items on the scale varied, with the largest gain seen in research methodology and communication of study findings.