Introduction Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges.

Estradiol and progesterone bind to their respective receptors in the hypothalamus and hippocampus to influence a variety of behavioral and physiological functions, including reproduction and cognition. Work from our lab and others has shown that the nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and SRC-2, are essential for efficient estrogen receptor (ER) and progestin receptor (PR) transcriptional activity in brain and for hormone-dependent behaviors. While the expression of SRC-1 in brain has been studied extensively, little is known about the expression of SRC-2 in brain. In the present studies, we found that SRC-2 was highly expressed throughout the hippocampus, amygdala and hypothalamus, including the medial preoptic area (MPOA), ventral medial nucleus (VMN), arcuate nucleus (ARC), bed nucleus of the stria terminalis, supraoptic nucleus and suprachiasmatic nucleus. In order for coactivators to function with steroid receptors, they must be expressed in the same cells. Indeed, SRC-2 and ERα were coexpressed in many cells in the MPOA, VMN and ARC, all brain regions known to be involved in female reproductive behavior and physiology. While in vitro studies indicate that SRC-2 physically associates with ER and PR, very little is known about receptor-coactivator interactions in brain. Therefore, we used pull-down assays to test the hypotheses that SRC-2 from hypothalamic and hippocampal tissue physically associate with ER and PR subtypes in a ligand-dependent manner. SRC-2 from both brain regions interacted with ERα bound to agonist, but not in the absence of ligand or in the presence of the selective ER modulator, tamoxifen. Analysis by mass spectrometry confirmed these ligand-dependent interactions between ERα and SRC-2 from brain. In dramatic contrast, SRC-2 from brain showed little to no interaction with ERβ. Interestingly, SRC-2 from both brain regions interacted with PR-B, but not PR-A, in a ligand-dependent manner. Taken together, these findings reveal that SRC-2 is expressed in brain regions known to mediate a variety of steroid-dependent functions. Furthermore, SRC-2 is expressed in many ERα containing cells in the hypothalamus. Finally, SRC-2 from brain interacts with ER and PR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain.

BackgroundThe absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.Methods/DesignSentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.DiscussionIn addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improves maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.

ObjectiveTo describe the characteristics and chief complaints of adults seeking emergency care at two Cambodian provincial referral hospitals.MethodsAdults aged 18 years or older who presented without an appointment at two public referral hospitals were enrolled in an observational study. Clinical and demographic data were collected and factors associated with hospital admission were identified. Patients were followed up 48 hours and 14 days after presentation.FindingsIn total, 1295 hospital presentations were documented. We were able to follow up 85% (1098) of patients at 48 hours and 77% (993) at 14 days. The patients’ mean age was 42 years and 64% (823) were females. Most arrived by motorbike (722) or taxi or tuk-tuk (312). Most common chief complaints were abdominal pain (36%; 468), respiratory problems (15%; 196) and headache (13%; 174). Of the 1050 patients with recorded vital signs, 280 had abnormal values, excluding temperature, on arrival. Performed diagnostic tests were recorded for 539 patients: 1.2% (15) of patients had electrocardiography and 14% (175) had diagnostic imaging. Subsequently, 783 (60%) patients were admitted and 166 of these underwent surgery. Significant predictors of admission included symptom onset within 3 days before presentation, abnormal vital signs and fever. By 14-day follow-up, 3.9% (39/993) of patients had died and 19% (192/993) remained functionally impaired.ConclusionIn emergency admissions in two public hospitals in Cambodia, there is high admission-to-death ratio and limited application of diagnostic techniques. We identified ways to improve procedures, including better documentation of vital signs and increased use of diagnostic techniques.

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Objective Provider‐performed endocervical sampling (PPES) in the diagnosis of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) may be difficult to perform in a busy emergency department (ED) due to patient preference, availability of the pelvic examination room, or provider availability. Our objective was to assess if self‐obtained vaginal swabs (SOVS) were noninferior to PPES in the ED diagnosis of NG/CT using a rapid nucleic acid amplification test (NAAT). Methods We conducted a prospective observational cohort study in a single ED. Participants were adult female English‐ and Spanish‐speaking patients in whom the ED provider felt that NG/CT testing was warranted. Each patient had SOVS and PPES performed. For SOVS, a research associate reviewed a one‐page handout describing the procedure but gave no other assistance. Patients answered survey questions regarding acceptability of SOVS and symptomatology. We established a minimum sensitivity of 90% for SOVS to be considered clinically noninferior to standard PPES. Results A total of 533 patients completed enrollment and answered survey questions, 515 of whom had laboratory results for both SOVS and PPES. There were 86 patients with a positive result: 29 with NG, 47 with CT, and 10 with coinfection. SOVS had a sensitivity of 95% (95% confidence interval = 88% to 99%) for the detection of NG/CT when compared to PPES. SOVS were felt to be an acceptable collection method in 93% of patients and 75% preferred SOVS to PPES. Conclusion SOVS are noninferior to PPES in NG/CT diagnosis using a rapid NAAT in ED patients and surveys indicate high patient acceptability.

BackgroundEmergency medicine is a young specialty in many low- and middle-income countries (LMICs). Although many patients seeking emergency or acute care are children, little information is available about the needs and current treatment of this group in LMICs. In this observational study, we sought to describe characteristics, chief complaints, management, and outcomes of children presenting for unscheduled visits to two Cambodian public hospitals.MethodsChildren enrolled in the study presented without appointment for treatment at one of two Cambodian public referral hospitals during a 4-week period in 2012. Researchers used standardized questionnaires and hospital records to collect demographic and clinical data. Patients were followed up at 48 h and 14 days after initial presentation. Multivariate logistic regression identified factors associated with hospital admission.ResultsThis study included 867 unscheduled visits. Mean patient age was 5.7 years (standard deviation 4.8 years). Of the 35 different presenting complaints, fever (63%), respiratory problems (25%), and skin complaints (24%) were most common. The majority of patients were admitted (51%), while 1% were transferred to another facility. Seven patients (1%) died within 14 days. Follow-up rates were 83% at 48 h and 75% at 14 days. Predictors of admission included transfer or referral from another health provider, seeking prior care for the presenting problem, low socioeconomic status, onset of symptoms within 24 h of seeking care, abnormal vital signs or temperature, and chief complaint of abdominal pain or fever.ConclusionsWhile the admission rate in this study was high, mortality was low. More effective identification and management of children who can be treated and released may free up scarce inpatient resources for children who warrant admission.Electronic supplementary materialThe online version of this article (10.1186/s12245-018-0172-0) contains supplementary material, which is available to authorized users.

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