Optimal Dose of Spinal Bupivacaine on Maternal and Fetal Outcomes in Parturients Undergoing Combined Technique for Labor Analgesia: A Randomized Double Blinded Prospective Study

Study Objectives: Maternal hypotension and fetal bradycardia (FB) are recognized complications of combined spinal epidural. Our purpose was to ascertain which of 3 common doses of spinal bupivacaine results in optimal analgesia with minimal side effects, assuming the lowest dose fills all criteria. Design: Prospective, randomized clinical trial. Setting: Labor and Delivery Unit of 514-bed urban teaching hospital. Patients, Interventions and Measurements: Patients were assigned to receive an intrathecal dose of 20 mcg of fentanyl with either 2.5 mg, 1.66 mg, or 1.25 mg of isobaric bupivacaine. Visual Analog Scale (VAS) Pain Score, fetal heart rate (FHR), maternal blood pressure (BP), number of hypotensive episodes, doses of vasopressors, nitroglycerin and mode of delivery were recorded at various time points. Main results: 164 patients were enrolled: 66 receiving 1.25 mg, 50 in the 1.66 mg group and 48 in the 2.5 mg. At 6 and 10 minutes, we recorded in the 1.66 mg group: 4.7% and 4.6%, 18.9% and 23.9% fewer hypotensive episodes compared with the 1.25 mg and the 2.5 mg groups respectively and significantly more hypotensive episodes in the 2.5 mg group (p = 0.025 and 0.019 respectively). There was no statistical difference in vasopressors use, mode of delivery or FB. The VAS decreased equally by an average of 7–10 points among all groups. Conclusion: The 1.66 mg spinal dose was associated with the least hypotensive episodes and equivalent pain relief as the 2.5 mg. The 1.25 mg and 1.66 mg doses allowed for adequate BP and FHR stability. Clinical Trial: Study registered on the ClinicalTrial.gov website under the NCT number NCT02159807

What information and the extent of information research participants need in informed consent forms: a multi-country survey

Background: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. Methods: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). Results: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be \u27moderately important\u27 to \u27very important\u27 for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). Conclusions: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF

Calcium-Dependent Hyperexcitability in Human Stem Cell–Derived Rett Syndrome Neuronal Networks

Background: Mutations in MECP2 predominantly cause Rett syndrome and can be modeled in vitro using human stem cell–derived neurons. Patients with Rett syndrome have signs of cortical hyperexcitability, such as seizures. Human stem cell–derived MECP2 null excitatory neurons have smaller soma size and reduced synaptic connectivity but are also hyperexcitable due to higher input resistance. Paradoxically, networks of MECP2 null neurons show a decrease in the frequency of network bursts consistent with a hypoconnectivity phenotype. Here, we examine this issue. Methods: We reanalyzed multielectrode array data from 3 isogenic MECP2 cell line pairs recorded over 6 weeks (n = 144). We used a custom burst detection algorithm to analyze network events and isolated a phenomenon that we termed reverberating super bursts (RSBs). To probe potential mechanisms of RSBs, we conducted pharmacological manipulations using bicuculline, EGTA-AM, and DMSO on 1 cell line (n = 34). Results: RSBs, often misidentified as single long-duration bursts, consisted of a large-amplitude initial burst followed by several high-frequency, low-amplitude minibursts. Our analysis revealed that MECP2 null networks exhibited increased frequency of RSBs, which produced increased bursts compared with isogenic controls. Bicuculline or DMSO treatment did not affect RSBs. EGTA-AM selectively eliminated RSBs and rescued network burst dynamics. Conclusions: During early development, MECP2 null neurons are hyperexcitable and produce hyperexcitable networks. This may predispose them to the emergence of hypersynchronic states that potentially translate into seizures. Network hyperexcitability depends on asynchronous neurotransmitter release that is likely driven by presynaptic Ca2+ and can be rescued by EGTA-AM to restore typical network dynamics

Melioidosis in northern Sri Lanka: filling the gap in the map

No abstract availabl