Abanti Sanyal

Randomized open-label trial of dextromethorphan in Rett syndrome

Objective: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. Methods: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist–Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Results: Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Conclusions: Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. Classification of evidence: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.

Nipple-Sparing Mastectomy Improves Long-Term Nipple But Not Skin Sensation After Breast Reconstruction: Quantification of Long-Term Sensation in Nipple Sparing Versus Non-nipple Sparing Mastectomy

Background Changes in breast sensation after reconstruction are expected. Return of breast sensation after reconstruction and whether nipple-sparing mastectomy offers a substantial benefit in terms of sensation has been inconsistently documented in the literature. We conducted the current study using the pressure-specified sensory device to quantify postoperative breast sensation in patients undergoing nipple-sparing versus non–nipple-sparing mastectomy. Methods Consecutive adult women who underwent nipple-sparing (NSM) and non-NSM (NNSM) and were at least 18 months postreconstruction were included. Breast measurements were taken in 4 quadrants (upper/lower lateral, upper/lower medial) and nipple. Averaged skin cutaneous thresholds [(UL+LL+UM+LM)/4] and nipple sensation between NSM and NNSM were compared as the primary outcome measure. A generalized estimating equations model was used; univariate and multivariate variable analyses were done when appropriate. Results Forty-four patients (74 breasts) were examined (53 NNSM vs 21 NSM). The groups were further subdivided into autologous versus implant-based reconstruction. Averaged cutaneous skin thresholds for quadrants were better for the NSM, 51.8(±24.5) g/mm2 versus NNSM, 56.5(±25.7) g/mm2, although this difference was not statistically significant. However, NSM breasts measured higher nipple or nipple area sensitivity, 44.5(±30.8) g/mm2 versus NNSM, 83.8(±27.4) g/mm2 (P < 0.001). In a multivariate regression analysis, a predictor of decreased sensation was the number of revision surgeries, especially after third revision. Conclusions Breast sensation is decreased after reconstruction in both NSM and NNSM, but nipple sensation or nipple area is better preserved in NSM breasts. Number of revision surgeries (>3) was a predictor of decreased sensation.

Vision Preference Value Scale and Patient Preferences in Choosing Therapy for Symptomatic Vitreomacular Interface Abnormality

Importance While symptomatic vitreomacular interface abnormalities (VIAs) are common, assessment of vision preference values and treatment preferences of these may guide treatment recommendations by physicians and influence third-party payers. Objective To determine preference values that individuals with VIA assign to their visual state and preferences of potential treatments. Design, Setting, and Participants In this cross-sectional one-time questionnaire study conducted between December 2015 and January 2017, 213 patients from tertiary care referral centers in Thailand, the United Kingdom, and the United States were studied. Patients with symptomatic VIA diagnosed within 1 year of data collection, visual acuity less than 20/20 OU, and symptoms ascribed to VIAs were included. Data were analyzed from January 2017 to November 2017. Main Outcomes and Measures The primary end points were overall mean preference value that individuals with VIA assigned to their visual state and patients’ preferences for potential treatments. Preference values were graded on a scale from 0 to 1, with 0 indicating death and 1 indicating perfect health with perfect vision. Results Of the 213 included patients, 139 (65.3%) were women, and the mean (SD) age was 65.6 (7.7) years. Diagnoses included epiretinal membrane (n = 100 [46.9%]), macular hole (n = 99 [46.5%]), and vitreomacular traction (n = 14 [6.6%]). The mean (SD) vision preference value was 0.76 (0.15), without differences identified among the 3 VIA types. More participants were enthusiastic about vitrectomy (150 [71.1%]) compared with intravitreal injection (120 [56.9%]) (difference, 14.2%; 95% CI, 5.16-23.3; P = .002). Adjusted analyses showed enthusiasm for vitrectomy was associated with fellow eye visual acuity (odds ratio, 10.99; 95% CI, 2.01-59.97; P = .006) and better-seeing eye visual acuity (odds ratio, 0.03; 95% CI, 0.001-0.66; P = .03). Overall enthusiasm for treatment was associated with fellow eye visual acuity (odds ratio, 7.22; 95% CI, 1.29-40.40; P = .02). Overall, most participants (171 [81.0%]) were enthusiastic about surgery, injection, or both. Conclusions and Relevance Study participants reported similar preference values among 3 types of VIAs. The data suggest that most patients with these conditions would be enthusiastic about undergoing vitrectomy or an injection to treat it, likely because of the condition’s effect on visual functioning, although there may be a slight preference for vitrectomy at this time.

Postpartum family planning integration with maternal, newborn and child health services: A cross-sectional analysis of client flow patterns in India and Kenya

Objectives Maternal, newborn and child health (MNCH) services represent opportunities to integrate postpartum family planning (PPFP). Objectives were to determine levels of MNCH–family planning (FP) integration and associations between integration, client characteristics and service delivery factors in facilities that received programmatic PPFP support. Design and setting Cross-sectional client flow assessment conducted during May–July 2014, over 5 days at 10 purposively selected public sector facilities in India (4 hospitals) and Kenya (2 hospitals and 4 health centres). Participants 2158 client visits tracked (1294 India; 864 Kenya). Women aged 18 or older accessing services while pregnant and/or with a child under 2 years. Interventions PPFP/postpartum intrauterine device—Bihar, India (2012–2013); Jharkhand, India (2009–2014); Embu, Kenya (2006–2010). Maternal, infant and young child nutrition/FP integration—Bondo, Kenya (2011–2014). Primary outcome measures Proportion of visits where clients received integrated MNCH–FP services, client characteristics as predictors of MNCH–FP integration and MNCH–FP integration as predictor of length of time spent at facility. Results Levels of MNCH–FP integration varied widely across facilities (5.3% to 63.0%), as did proportion of clients receiving MNCH–FP integrated services by service area. Clients travelling 30–59 min were half as likely to receive integrated services versus those travelling under 30 min (OR 0.5, 95% CI 0.4 to 0.7, P<0.001). Clients receiving MNCH–FP services (vs MNCH services only) spent an average of 10.5 min longer at the facility (95% CI −0.1 to 21.9, not statistically significant). Conclusions Findings suggest importance of focused programmatic support for integration by MNCH service area. FP integration was highest in areas receiving specific support. Integration does not seem to impose an undue burden on clients in terms of time spent at the facility. Clients living furthest from facilities are least likely to receive integrated services.

Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype

Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with MECP2 mutations underwent baseline neurological evaluation (KKI‐RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study. Mean QTc of the cohort was 422.6 msec, which did not exceed the normal values for age. 7/100 patients (7%) had QTc prolongation (>450 msec). There was a trend for increasing QTc with age and clinical severity (P = 0.09). No patients with R106C, R106W, R133C, R168*, R270*, R294*, R306C, R306H, and R306P mutations demonstrated QTc prolongation. There was a relatively high proportion of QTc prolongation in patients with R255* mutations (2/8, 25%) and large deletions (1/4, 25%). The overall presence of QTc prolongation did not correlate with mutation category (P = 0.52). Our findings demonstrate that in RTT, the prevalence of QTc prolongation is lower than previously reported. Hence, all RTT patients warrant baseline ECG; if QTc is prolonged, then cardiac followup is warranted. If initial QTc is normal, then annual ECGs, particularly in younger patients, may not be necessary. However, larger sample sizes are needed to solidify the association between QTc and age and clinical severity. The biological and clinical significance of mild QTc prolongation above the normative data remains undetermined.

NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of Normal Pressure Hydrocephalus.

Introduction: Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests. Material and Methods: Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication. Results: The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007). Conclusions: LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes.

Smartphone Use and the Perception of Professionalism Among Medical Students and Surgical Faculty

OBJECTIVE To understand the perception of professionalism surrounding smartphone use (wards/educational activities) among medical students and surgical faculty. DESIGN A prospective cohort study was conducted using an electronic survey and distributed to third- and fourth-year medical students, obstetrics/gynecology, and surgery faculty members. Five cases were randomly presented; participants were asked to review and rate the clinicians behavior on a 5-point Likert scale. SETTING The study was completed at The Johns Hopkins University School of Medicine, a tertiary care institution, in the departments of gyn/ob and surgery. PARTICIPANTS A total of 123 medical students (51% response rate) from the class of 2015/2016 along with 73 surgical faculty in the departments of gyn/ob and surgery completed the study. Of the surgical faculty, 48% were ob/gyn (54% response rate) and 52% were surgery (21% response rate). Of note, when quarrying the department of surgery all surgical faculty were included, however, only those with direct student interaction were asked to complete the survey leading to the lower response rate. RESULTS In 3 of 5 scenarios, students and faculty had significant differences in perception of professionalism (p<0.05). Faculty were more likely to find behaviors unprofessional compared to students. The acceptability of certain behaviors was significantly correlated in some case scenarios with how participants reported using their smartphones. Personal use of technology appears to influence the perception of acceptable behavior in certain scenarios.

Diagnostic Assessment of Adult Hydrocephalus Log compared to standard normal pressure hydrocephalus diagnostic tools

Median age at presentation was 76 (71-80) years old. TUG (p 0.05). LP log improvement was associated with surgical indication OR: 24.5 95%CI (2.4248.12) (p=0.007). Conclusions LP log showed a higher sensitivity and diagnostic accuracy detecting clinical differences in NPH than the current diagnostic approach. Our next step is to conduct a cross-validation analysis of the diagnostic and prognostic accuracy of this new tool.