Multiplex PCR for bacterial, viral and protozoal pathogens in persistent diarrhoea or persistent abdominal pain in Côte d'Ivoire, Mali and Nepal.

In contrast to acute diarrhoea, the aetiology of persistent digestive disorders (≥ 14 days) is poorly understood in low-resource settings and conventional diagnostic approaches lack accuracy. In this multi-country study, we compared multiplex real-time PCR for enteric bacterial, parasitic and viral pathogens in stool samples from symptomatic patients and matched asymptomatic controls in Côte d'Ivoire, Mali and Nepal. Among 1826 stool samples, the prevalence of most pathogens was highest in Mali, being up to threefold higher than in Côte d'Ivoire and up to tenfold higher than in Nepal. In all settings, the most prevalent bacteria were EAEC (13.0-39.9%) and Campylobacter spp. (3.9-35.3%). Giardia intestinalis was the predominant intestinal protozoon (2.9-20.5%), and adenovirus 40/41 was the most frequently observed viral pathogen (6.3-25.1%). Significantly different prevalences between symptomatic and asymptomatic individuals were observed for Campylobacter, EIEC and ETEC in the two African sites, and for norovirus in Nepal. Multiple species pathogen infection was common in Côte d'Ivoire and Mali, but rarely found in Nepal. We observed that molecular testing detected multiple enteric pathogens and showed low discriminatory accuracy to distinguish between symptomatic and asymptomatic individuals. Yet, multiplex PCR allowed for direct comparison between different countries and revealed considerable setting-specificity.

Interventional treatments.

In migraine, when patients have failed medication management or are unable to be treated with systemic medications, minimally invasive interventions can be options used to provide pain relief. The type of intervention depends on the pain location, associated clinical features, clinical context, medical comorbidities, and response to prior injections. Interventions can vary from bedside peripheral nerve blocks to fluoroscopically guided interventions. Growing evidence is supporting the use of interventions in migraine, and judicious use can improve clinical outcomes.

Major histocompatibility complex (MHC) gene frequency in acquired dermal macular hyperpigmentation: a case control study.

BACKGROUND: Human leukocyte antigen (HLA) allele frequencies have a known association with the pathogenesis of various autoimmune diseases. METHODS: We recruited 31 Indian patients of acquired dermal macular hyperpigmentation (ADMH) and 60 unrelated, age-and-gender-matched healthy controls. After history and clinical examination, 5 ml of blood in EDTA vials was collected. These samples were subjected to DNA extraction and the expression of HLA A, B, C, DR, DQ-A, and DQ-B was studied. RESULTS: There was a predominance of females with a gender ratio of 23 : 8 and the most common phototype was Fitzpatrick type IV (83.9%). There was a significant association of HLA A*03:01 (OR: 5.8, CI: 1.7-17.0, P = 0.005), HLA B*07:02 (OR: 5.3, CI: 1.9-14.6, P = 0.003), HLA C*07:02 (OR: 4.3, CI: 1.8-9.6, P = 0.001), HLA DRB1*10:01 (OR: 7.6, CI: 1.7-38.00, P = 0.022), and HLA DRB1*15:02 (OR: 31.0, CI: 4.4-341.8, P < 0.001) with patients compared to controls, whereas HLA DQB*03:01 was less associated with patients compared to controls (OR: 0.2, CI: 0.0-0.6, P = 0.009). CONCLUSION: Patients with ADMH are more likely to have the HLA A*03:01, HLA B 07*02, HLA C*07:02, HLA DRB1*10:01, HLA DRB1*15:02 and less likely to have the HLA DQB*03:01 allele. Larger cohort studies may thus be conducted studying these specific alleles.

The Key Areas and Unmet Need of Mentorship Programs in Indian Dermatology: A Survey Based Analysis.

Background: Mentorship programs for dermatologists have been in vogue in the West for many years, but have been on a hiatus in India. Recently, there is renewed interest, and mentorship programs are gaining momentum across the country to guide and nurture young dermatologists to attain their full potential. However, what constitutes an ideal mentorship program is still an enigma. Materials and Methods: We developed a multiple-choice questionnaire (Google-form), enquiring post graduates and dermatologists about their general opinion of mentorship, its key areas and what constituted an ideal mentorship-program. These were distributed via email and WhatsApp and responses were collected over a month's period. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) for Windows. Results: We received 202 responses and majority of the respondents were private practitioners (32.2%) and post graduate students (29.7%). Respondents felt that mentorship should be undertaken at the beginning of postgraduation (37.1%) or just after its completion (23.8%), and should focus on academic and research related issues (55.0%). Communication (95.5%) was an important factor for the program to be successful, and on an average, must be of seven weeks duration, with a mentor : mentee ratio of 1:2. We found a significant association between the designation of the respondent and their perceived ideal time for a mentorship program (P<0.001, Chi Square Test), seeking of mentorship beyond the program duration (P<0.01, Chi Square Test) and the type of mentorship program (P=0.01, Chi square test). Conclusion: Our survey concluded that a well-planned short mentorship program of six to eight weeks duration with a low mentee to mentor ratio with an informal style of mentoring in the formative years of one's career would be suitable in the Indian Dermatology scenario. Communication and availability emerged as important elements for a successful mentor mentee relationship. The positive effects of a well-planned mentorship program extend beyond its duration and enrich both the mentor and mentee.

The ongoing risk of Leishmania donovani transmission in eastern Nepal: an entomological investigation during the elimination era.

BACKGROUND: Visceral leishmaniasis (VL), a life-threatening neglected tropical disease, is targeted for elimination from Nepal by the year 2026. The national VL elimination program is still confronted with many challenges including the increasingly widespread distribution of the disease over the country, local resurgence and the questionable efficacy of the key vector control activities. In this study, we assessed the status and risk of Leishmania donovani transmission based on entomological indicators including seasonality, natural Leishmania infection rate and feeding behavior of vector sand flies, Phlebotomus argentipes, in three districts that had received disease control interventions in the past several years in the context of the disease elimination effort. METHODS: We selected two epidemiologically contrasting settings in each survey district, one village with and one without reported VL cases in recent years. Adult sand flies were collected using CDC light traps and mouth aspirators in each village for 12 consecutive months from July 2017 to June 2018. Leishmania infection was assessed in gravid sand flies targeting the small-subunit ribosomal RNA gene of the parasite (SSU-rRNA) and further sequenced for species identification. A segment (~ 350 bp) of the vertebrate cytochrome b (cytb) gene was amplified from blood-fed P. argentipes from dwellings shared by both humans and cattle and sequenced to identify the preferred host. RESULTS: Vector abundance varied among districts and village types and peaks were observed in June, July and September to November. The estimated Leishmania infection rate in vector sand flies was 2.2% (1.1%-3.7% at 95% credible interval) and 0.6% (0.2%-1.3% at 95% credible interval) in VL and non-VL villages respectively. The common source of blood meal was humans in both VL (52.7%) and non-VL (74.2%) villages followed by cattle. CONCLUSIONS: Our findings highlight the risk of ongoing L. donovani transmission not only in villages with VL cases but also in villages not reporting the presence of the disease over the past several years within the districts having disease elimination efforts, emphasize the remaining threats of VL re-emergence and inform the national program for critical evaluation of disease elimination strategies in Nepal.

Quantitative assessment of painful diabetic peripheral neuropathy after high-frequency spinal cord stimulation: a pilot study.

OBJECTIVE: Randomized trials have demonstrated efficacy of spinal cord stimulation (SCS) for treatment of painful diabetic neuropathy (PDN). Preliminary data suggested that treatment of PDN with high-frequency SCS resulted in improvements on neurological examination. The purpose of the present study was to explore whether patients with PDN treated with high-frequency SCS would have improvements in lower-extremity peripheral nerve function. DESIGN: Prospective cohort study in an outpatient clinical practice at a tertiary care center. METHODS: Patients with PDN were treated with high-frequency SCS and followed up for 12 months after SCS implantation with clinical outcomes assessments of pain intensity, neuropathic symptoms, and neurological function. Small-fiber sudomotor function was assessed with the quantitative sudomotor axon reflex test (QSART), and large-fiber function was assessed with nerve conduction studies (NCS). Lower-extremity perfusion was assessed with laser Doppler flowmetry. RESULTS: Nine patients completed 12-month follow-up visits and were observed to have improvements in lower-extremity pain, weakness, and positive sensory symptoms. Neuropathy impairment scores were improved, and 2 patients had recovery of sensory responses on NCS. A reduction in sweat volume on QSART was observed in the proximal leg but not at other sites. No significant differences were noted in lower-extremity perfusion or NCS as compared with baseline. CONCLUSIONS: The improvement in pain relief was concordant with improvement in neuropathy symptoms. The findings from this study provide encouraging preliminary data in support of the hypothesis of a positive effect of SCS on peripheral neuropathy, but the findings are based on small numbers and require further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03769675.

Prescribing practices of tranexamic acid for melasma: Delphi consensus from the Pigmentary Disorders Society.

Introduction There is ambiguity regarding usage of tranexamic acid for melasma in India, be it in its pre-administration evaluation, administration route, dosing or monitoring. Hence, we conducted this study to understand various tranexamic-acid prescribing patterns and provide practical guidelines. Materials and methods A Google-form-based questionnaire (25-questions) was prepared based on the key areas identified by experts from the Pigmentary Disorders Society, India and circulated to practicing dermatologists across the country. In rounds 2 and 3, the questionnaire was re-presented to the same group of experts and their opinions were sought. The results of the practitioners' survey were denoted graphically alongside, to guide them. Consensus was deemed when at least 80% of respondents chose an option. Results The members agreed that history pertaining to risk factors for thromboembolism, cardiovascular and menstrual disorders should be sought in patients being started on oral tranexamic-acid. Baseline coagulation profile should be ordered in all patients prior to tranexamic-acid and more exhaustive investigations such as complete blood count, liver function test, protein C and S in patients with high risk of thromboembolism. The preferred oral dose was 250 mg orally twice daily, which can be used alone or in combination with topical hydroquinone, kojic acid and sunscreen. Repeated dosing of tranexamic-acid may be required for those relapsing with melasma following initial tranexamic-acid discontinuation. Coagulation profile should ideally be repeated at three monthly intervals during follow-up, especially in patients with clinically higher risk of thromboembolism. Treatment can be stopped abruptly post improvement and no tapering is required. Limitation This study is limited by the fact that open-ended questions were limited to the first general survey round. Conclusion Oral tranexamic-acid provides a valuable treatment option for melasma. Frequent courses of therapy may be required to sustain results and a vigilant watch is recommended for hypercoagulable states during the course of therapy.

Consensus Practice Guidelines on Postdural Puncture Headache From a Multisociety, International Working Group: A Summary Report.

Importance: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective: To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review: With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings: After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance: Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

Evidence-based clinical practice guidelines on postdural puncture headache: a consensus report from a multisociety international working group.

INTRODUCTION: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis or management of this condition is, however, currently lacking. This multisociety guidance aims to fill this void and provide practitioners with comprehensive information and patient-centric recommendations to prevent, diagnose and manage patients with PDPH. METHODS: Based on input from committee members and stakeholders, the committee cochairs developed 10 review questions deemed important for the prevention, diagnosis and management of PDPH. A literature search for each question was performed in MEDLINE (Ovid) on 2 March 2022. The results from each search were imported into separate Covidence projects for deduplication and screening, followed by data extraction. Additional relevant clinical trials, systematic reviews and research studies published through March 2022 were also considered for the development of guidelines and shared with contributors. Each group submitted a structured narrative review along with recommendations graded according to the US Preventative Services Task Force grading of evidence. The interim draft was shared electronically, with each collaborator requested to vote anonymously on each recommendation using two rounds of a modified Delphi approach. RESULTS: Based on contemporary evidence and consensus, the multidisciplinary panel generated 50 recommendations to provide guidance regarding risk factors, prevention, diagnosis and management of PDPH, along with their strength and certainty of evidence. After two rounds of voting, we achieved a high level of consensus for all statements and recommendations. Several recommendations had moderate-to-low certainty of evidence. CONCLUSIONS: These clinical practice guidelines for PDPH provide a framework to improve identification, evaluation and delivery of evidence-based care by physicians performing neuraxial procedures to improve the quality of care and align with patients' interests. Uncertainty remains regarding best practice for the majority of management approaches for PDPH due to the paucity of evidence. Additionally, opportunities for future research are identified.

Spina bifida occulta with the persistent spinous process in living: A three-dimensionally reconstructed sacrum from computed tomographic imaging.

Background: Here we aim to report the persistent spinous process in the 'pan sacral type' of spina bifida occulta in an asymptomatic male and discuss its clinical significance. The presence of this type of dorsal wall defect with a bony spur attached to it has never been described in the literature to the best of our knowledge after extensive literature search. Our work presents the first anatomic description where the spinous and paraspinous cleft are seen in a sacrum of a live subject. Case Report: During a morphometric study of the sacra, normal subject computed tomography imaging (CT) was procured from the Department of Radio-diagnosis. A three-dimensional (3D) image of the sacrum was created using Dicom to Print and Geomagic freeform plus software. A complete dorsal wall defect was observed in a 3D reconstructed sacrum of an adult male. The sacral canal was converted into a groove with a bony spur hanging in the centre. The longitudinal bony spur attached to the lamina was the persistent spinous process. Conclusion: Such congenital defects are clinically significant for the anaesthetist during caudal epidural block and for orthopaedic surgeons before any surgical procedure. It may be misdiagnosed as an abnormal bony injury on CT. Thus, it is essential to ensure that patients with congenital anomalies are not treated unnecessarily for spinal fractures.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

Incremental diagnostic yield and clinical outcomes of lateral decubitus CT myelogram immediately following negative lateral decubitus digital subtraction myelogram.

INTRODUCTION: Spontaneous intracranial hypotension (SIH) caused by a spinal cerebrospinal fluid (CSF) leak classically presents with orthostatic headache. Digital subtraction myelography (DSM) has a well-established diagnostic yield in the absence of extradural spinal collection. At our institution, DSM is followed by lateral decubitus CT myelogram (LDCTM) in the same decubitus position to increase diagnostic yield of the combined study. We evaluated the incremental diagnostic yield of LDCTM following negative DSM and reviewed patient outcomes. METHODS: Retrospective review of consecutive DSMs with subsequent LDCTM from April 2019 to March 2021 was performed. Combined reports were reviewed, and studies with positive DSMs were excluded. Of the exams with negative DSM, only studies with LDCTM reports identifying potential leak site were included. Interventions and follow-up clinical notes were reviewed to assess symptoms improvement following treatment. RESULTS: Of the 83 patients with negative DSMs, 11 (13.2%) had positive leak findings on LDCTMs, and 21 (25.3%) were equivocal. Of 11 positive LDCTMs, 6 leaks were nerve sheath tears (NSTs) and 5 were CSF-venous fistulas (CVFs). 10/11 (90.9%) had intervention and follow-up, with 9/10 (90%) having positive clinical outcome. Of the 21 equivocal LDCTM patients (19 CVFs and 2 NSTs), 15 (71.4%) had interventions and follow-up, with 3/15 (20.0%) with positive clinical outcomes. CONCLUSION: LDCTM following negative DSM has an incremental diagnostic yield up to 38.6%, with up to 14.5% of positive patient outcomes following treatment. LDCTM should be considered after DSM to maximize diagnostic yield of the combined exam.

Long term outcomes of occipital nerve stimulation.

Background: Occipital nerve stimulation (ONS) has been investigated as a potential treatment for disabling headaches and has shown promise for disorders such as chronic migraine and cluster headache. Long term outcomes stratified by headache subtype have had limited exploration, and literature on outcomes of this neuromodulatory intervention spanning 2 or more years is scarce. Measures: We performed a narrative review on long term outcomes with ONS for treatment of headache disorders. We surveyed the available literature for studies that have outcomes for 24 months or greater to see if there is a habituation in response over time. Review of the literature revealed evidence in treatment of occipital neuralgia, chronic migraine, cluster headache, cervicogenic headache, short lasting unilateral neuralgiform headache attacks (SUNHA) and paroxysmal hemicrania. While the term "response" varied per individual study, a total of 17 studies showed outcomes in ONS with long term sustained responses (as defined per this review) in the majority of patients with specific headache types 177/311 (56%). Only 7 studies in total (3 cluster, 1 occipital neuralgia, 1 cervicogenic headache, 1 SUNHA, 1 paroxysmal hemicrania) provided both short-term and long-term responses up to 24 months to ONS. In cluster headache, the majority of patients (64%) were long term responders (as defined per this review) and only a minority of patients 12/62 (19%) had loss of efficacy (e.g., habituation). There was a high number 313/439 (71%) of adverse events per total number of patients in the studies including lead migration, requirements of revision surgery, allergy to surgical materials, infection and intolerable paresthesias. Conclusions: With the evidence available, the response to ONS was sustained in the majority of patients with cluster headache with low rates of loss of efficacy in this patient population. There was a high percent of adverse events per number of patients in long term follow-up and likely related to the off-label use of leads typically used for spinal cord stimulation. Further longitudinal assessments of outcomes in occipital nerve stimulation with devices labelled for use in peripheral nerve stimulation are needed to evaluate the extent of habituation to treatment in headache.

Morphometry and morphological analysis of carotico-clinoid foramen: an anatomical study with clinical implications.

BACKGROUND: The dural fold between anterior and middle clinoid processes on mineralisation leads to the formation of caroticoclinoid foramen (CCF). Different morphology of this foramen presents with different clinical features. The present study reports the frequency of CCF in the population of Bihar, while providing an account of assimilated information from previous literature regarding the association of caroticoclinoid ligament ossification with age and human genetics. MATERIALS AND METHODS: The study was conducted on 100 adult dry human skulls of unknown age and sex, and 50 lateral view radiographs of the head. RESULTS: Of the 100 dry skull bones, 9 presented with different forms of CCF. Bilateral complete foramina were noticed in 2 (2%) skull bones, while the incomplete foramina were observed bilaterally in 3 (3%) and unilaterally in 4 (4%) skulls. The lateral view radiograph data (n = 50) presented with a bilateral foramen in one subject and unilateral complete CCF in two different subjects. On measurements of the diameters of the complete CCF the mean values observed were 4.06 mm and 4.51 mm on the right side, while that on the left side were 5.15 mm and 4.14 mm. For the incomplete foramina, the mean values for the vertical diameter were 4.48 mm on the right and 4.19 mm on the left side, respectively. CONCLUSIONS: The frequency of CCF in the present study population of Bihar was much lesser than that of previously studied populations. However, the variation in frequency of different morphological types of CCF was observed to be the same across populations. The variations in CCF's metric data could help in predicting the morphological changes it causes to the clinoidal segment of the internal carotid artery, as well as in distinguishing its varieties.