Localised erythema nodosum leprosum-A rare entity managed with thalidomide.

Leprosy is caused by Mycobacterium leprae. The condition primarily affects the skin and peripheral nerves. There are two types of leprosy reactions, Type 1 and Type 2 or erythema nodosum leprosum (ENL). ENL is a severe multi-system, immune-mediated complication of lepromatous leprosy. It is characterised by widespread painful cutaneous nodules, fever and peripheral oedema. This report discusses the unusual case of a 29-year-old woman who developed a localised form of ENL which required thalidomide to induce remission.

Use of Injectable Platelet-Rich Fibrin Accompanied by Bone Graft in Socket Endurance: A Radiographic and Histological Study.

Background Ridge preservation became a crucial dental health issue and strategy to keep away from ridge defacement after post-tooth loss. The recent scientific evolution of platelet-rich fibrin (PRF) comprises a parenteral formulation of PRF. The combined allograft for socket preservation gives benefits. In this study, bone allografts, demineralized freeze-dried bone allografts (DFDBA) and freeze-dried bone allografts (FDBA) are used in a 30:70 ratio alone or in combination with injectable PRF (I-PRF) for socket preservation. Methods This study is a radiographic and histological examination conducted on 60 participants aged between 19-65 years. Participating patients agreed voluntarily that they would not bear any fixed prosthesis for the next nine months and plan for implanted teeth placement, including multi-rooted mandibular molars denticles. Both groups received atraumatic extraction; then, the socket was preserved with bone allograft alone in the control group and bone allograft mixed with I-PRF, forming sticky bone, in the experimental group. Clinical, radiological, and histological assessments were taken at the inception stage, three months, six months, and nine months. A multivariate regression model and a generalized estimating equation (GEE) model were used to analyse the effects of these changes on outcomes. Results In all the parameters, the test group indicated a good amount of bone growth with increasing intervals of time for bone height radiographically with statistically significant difference present (p<0.05) and histologically after nine months when socket site grafted with bone graft in combination with I-PRF. Conclusion This study's results demonstrated that I-PRF possesses the potential to regenerate and heal in the tooth-extracted socket. This study further recommends the implementation of I-PRF in safeguarding and conserving the raised rim of the tooth. Future research should take place on the osteogenic capability of I-PRF in more comprehensive ridge accession surgical procedures and additional expanding and improving capacities in periodontal reconstruction.

Findings of Epstein-Barr Virus Large B-Cell Lymphoma in a Patient With a History of Rectal Adenocarcinoma: A Case Report.

Colorectal adenocarcinoma is the neoplastic proliferation of glandular tissue in the distal gastrointestinal system and can be managed using surgical resection, novel chemotherapeutic regimens, and radiation therapy. Epstein-Barr virus (EBV) is a common double-stranded DNA virus that has the potential to transform B-cells into lymphoproliferative disorders given the presence of particular conditions such as immunocompromised and chronic inflammatory states. Colorectal cancer is one of the most common malignancies worldwide; however, the additional finding of EBV-positive lymphoma in a patient with a history of colorectal malignancy is uncommon, and this phenomenon has not been thoroughly explored. This report investigates the association between rectal adenocarcinoma and EBV-positive large B-cell lymphoma in an 87-year-old Caucasian male residing in the United States and explores possible causes for this occurrence.

Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

AIMS: We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). METHODS AND RESULTS: We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. CONCLUSION: In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Evaluating Strategies to Promote Effective, Multidisciplinary Team Collaboration in School Mental Health.

Multidisciplinary teams of school- and community-employed mental health, health, and educational staff work together in schools to offer a full continuum of mental health promotion, prevention, early intervention, and treatment services and supports. Intentional teaming structures and practices are essential to ensure teams deliver effective, coordinated services and supports. The current study investigated the extent to which continuous quality improvement strategies improved school mental health team performance during a 15-month national learning collaborative for 24 school district teams. All teams significantly improved their average teaming performance from baseline to the end of the collaborative (t(20) = -5.20, p < .001). Plan-Do-Study-Act (PDSA) cycles allowed teams to rapidly evaluate specific quality improvement changes to improve their performance. Teams with the most improvement focused on increasing multidisciplinary team membership, avoiding duplication and promoting efficiency, and connecting to community mental health providers/resources.

Gingival Crevicular Blood Glucose as a Novel Method for Screening Diabetes Mellitus in Periodontally Compromised Patients.

INTRODUCTION: Patients with periodontitis are significantly more likely to have undetected diabetes mellitus (DM). Self­monitoring devices like glucometers provide a simple method for rapid monitoring of the glucose level in blood by utilizing a blood sample from the finger, but this method requires puncturing to obtain blood. Bleeding from the gingival sulcus, obtained during oral hygiene examination, can be utilized for screening DM patients. Therefore, this study was performed with the aim of determining the efficacy of gingival crevicular blood as a non-invasive screening method for DM patients, as well as correlating and comparing gingival crevicular blood glucose (GCBG) levels with finger capillary blood glucose (FCBG) and fasting blood glucose (FBG) among non-diabetic and diabetic group patients. METHODS: In this cross-sectional comparative study, a total of 120 participants having moderate to severe gingivitis/periodontitis with an age range of 40 to 65 years were divided into two groups on the basis of FBG range taken from an antecubital vein: non-diabetic (≤126, n=60) and diabetic (≥126, n=60) groups. Blood oozing during the routine periodontal examination from the periodontal pocket was recorded using a test strip of a glucose self-monitoring device (AccuSure®Simple) as GCBG. Concomitantly FCBG was collected from the fingertip. These three parameters were statistically analyzed using the Student's t-test and the one-way ANOVA test and correlated with Pearson's correlation coefficient for both groups. RESULTS: The mean and standard deviation for the three parameters GCBG, FBG, and FCBG were 93.78±12.03, 89.98±13.22, and 93.08±15.56, respectively, for the non-diabetic group and 154.52±45.05, 159±47.00, and 162.23±50.60 subsequently for the diabetic group. Comparing glucose level parameters among the non-diabetic and diabetic groups suggests a significant difference with the p-value <0.001*(inter-group). ANOVA test was done for both groups suggesting no significant difference among these three methods of measuring blood glucose level, where the p-value found was 0.272 for the non-diabetic and 0.665 for the diabetic group (intra-group comparison). Pearson's correlation values suggested a good positive correlation for the non-diabetic group, with parameters GCBG and FBG (r=0.864), GCBG and FCBG (r=0.936), and FBG and FCBG (r=0.837). The diabetic group's Pearson's correlation suggested a highly significant positive correlation between three different methods in which GCBG and FBG (r=0.978), GCBG and FBG (r=0.977), and FBG and FCBG (r= 0.982). CONCLUSION: Blood oozing from the periodontal pocket during routine oral hygiene examination can be utilized by dental healthcare professionals to screen pre-diabetic patients which can be used as a simple and less invasive method for DM patients.

A small-molecule PI3Kα activator for cardioprotection and neuroregeneration.

Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1-5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling. 1938 allosterically activates PI3Kα through a distinct mechanism by enhancing multiple steps of the PI3Kα catalytic cycle and causes both local and global conformational changes in the PI3Kα structure. This compound is selective for PI3Kα over other PI3K isoforms and multiple protein and lipid kinases. It transiently activates PI3K signalling in all rodent and human cells tested, resulting in cellular responses such as proliferation and neurite outgrowth. In rodent models, acute treatment with 1938 provides cardioprotection from ischaemia-reperfusion injury and, after local administration, enhances nerve regeneration following nerve crush. This study identifies a chemical tool to directly probe the PI3Kα signalling pathway and a new approach to modulate PI3K activity, widening the therapeutic potential of targeting these enzymes through short-term activation for tissue protection and regeneration. Our findings illustrate the potential of activating kinases for therapeutic benefit, a currently largely untapped area of drug development.

Prognosis of pulmonary arterial hypertension patients with pericardial effusion before and after initiation of parenteral prostacyclin therapy.

Few studies have evaluated the effects of pulmonary arterial hypertension therapies on pericardial effusion. We evaluated hemodynamics, echocardiograms, and outcomes for 119 parenteral prostanoid-treated patients. We discovered an increased frequency of pericardial effusions posttreatment, and that a moderate-large pericardial effusion at initiation, but not at 1st follow-up, was significantly associated with mortality.

Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity.

N-Acyl indolines 4 are potent, non-covalent Notum inhibitors developed from a covalent virtual screening hit 2a. The lead compounds were simple to synthesise, achieved excellent potency in a biochemical Notum-OPTS assay and restored Wnt signalling in a cell-based TCF/LEF reporter assay. Multiple high resolution X-ray structures established a common binding mode of these inhibitors with the indoline bound centred in the palmiteolate pocket with key interactions being aromatic stacking and a water mediated hydrogen bond to the oxyanion hole. These N-acyl indolines 4 will be useful tools for use in vitro studies to investigate the role of Notum in disease models, especially when paired with a structurally related covalent inhibitor (e.g. 4w and 2a). Overall, this study highlights the designed switch from covalent to non-covalent Notum inhibitors and so illustrates a complementary approach for hit generation and target inhibition.

Perforated Emphysematous Cholecystitis: A Race Against Time.

Emphysematous cholecystitis is a rare infection of the gallbladder that stems from acute cholecystitis. It can rapidly progress and perforate the gallbladder, which would require urgent surgical intervention. A perforated gallbladder can be diagnosed using an abdominal computed tomography by confirming the presence of air in the gallbladder lumen with adjacent extraluminal air. The causes of ruptured emphysematous cholecystitis include, but are not limited to, diabetes, atherosclerotic changes in blood vessels, and infection with Clostridium perfringens, Escherichia coli, and Klebsiella spp., and is usually present in diabetic men. We report on a 57-year-old female who developed gall bladder perforation with an overflow of gallstones into the peritoneum without a history of diabetes or atherosclerotic disease. Due to the vast availability of computerized tomography and early surgical intervention, the rate of mortality due to perforated emphysematous cholecystitis has decreased over the last few decades.

Analysis of serum microRNA-122 in a randomized controlled trial of N-acetylcysteine for treatment of antituberculosis drug-induced liver injury.

AIM: Serum microRNA-122 (miR-122) is a novel biomarker for drug-induced liver injury, with good sensitivity in the early diagnosis of paracetamol-induced liver injury. We describe miR-122 concentrations in participants with antituberculosis drug-induced liver injury (AT-DILI). We explored the relationship between miR-122 and alanine aminotransferase (ALT) concentrations and the effect of N-acetylcysteine (NAC) on miR-122 concentrations. METHODS: We included participants from a randomized placebo-controlled trial of intravenous NAC in AT-DILI. ALT and miR-122 concentrations were quantified before and after infusion of NAC/placebo. We assessed correlations between ALT and miR-122 concentrations and described changes in ALT and miR-122 concentrations between sampling occasions. RESULTS: We included 45 participants; mean age (± standard deviation) 38 (±10) years, 58% female and 91% HIV positive. The median (interquartile range) time between pre- and post-infusion biomarker specimens was 68 h (47-77 h). The median pre-infusion ALT and miR-122 concentrations were 420 U/L (238-580) and 0.58 pM (0.18-1.47), respectively. Pre-infusion ALT and miR-122 concentrations were correlated (Spearman's ρ = .54, P = .0001). Median fold-changes in ALT and miR-122 concentrations between sampling were 0.56 (0.43-0.69) and 0.75 (0.23-1.53), respectively, and were similar in the NAC and placebo groups (P = .40 and P = .68 respectively). CONCLUSIONS: miR-122 concentrations in our participants with AT-DILI were considerably higher than previously reported in healthy volunteers and in patients on antituberculosis therapy without liver injury. We did not detect an effect of NAC on miR-122 concentrations. Further research is needed to determine the utility of miR-122 in the diagnosis and management of AT-DILI.

Pre-Hematopoietic Stem Cell Transplantation Rituximab for Epstein-Barr Virus and Post-Lymphoproliferative Disorder Prophylaxis in Alemtuzumab Recipients.

Epstein-Barr virus (EBV) reactivation and EBV-related post-transplantation lymphoproliferative disorder (PTLD) are often fatal complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of EBV reactivation may be mitigated by depletion of B cells with rituximab. Starting in January 2020, allo-HSCT recipients undergoing T-cell depletion with alemtuzumab received 1 dose of rituximab before transplantation. The objective of this study was to evaluate the cumulative incidence of EBV reactivation and EBV-PTLD in recipients of allo-HSCT and in vivo T-cell depletion with alemtuzumab who received pre-HSCT rituximab compared to patients who did not. This was a single-center retrospective analysis of adult patients who consecutively received an HLA-identical allo-HSCT between January 2019 and May 2021 and in vivo T-cell depletion with alemtuzumab. Patients were included in the rituximab cohort if they received rituximab within 6 months before their transplantation. The primary endpoint was incidence of EBV reactivation at day 180 among those receiving pre-HSCT rituximab versus those not receiving rituximab. Secondary endpoints included cumulative incidence of EBV-PTLD at 1 year, time to engraftment, immune reconstitution, and incidence of infections and acute graft-versus-host disease (aGVHD) at day 180. Eighty-six consecutive patients who received an allo-HSCT with alemtuzumab T-cell depletion were reviewed; 43 patients who received pre-HSCT rituximab after our protocol modification were compared to 43 patients who did not receive pre-HSCT rituximab before this change. Median age was 57 (interquartile range [IQR] 40-69) years, and the majority of patients had acute myeloid leukemia or myelodysplastic syndrome. Baseline characteristics were similar between the cohorts. EBV reactivation at day 180 occurred in 23 (53%) patients without prior rituximab exposure versus 0 patients with pre-HSCT rituximab exposure (P < .0001). Similarly, 6 patients without prior rituximab exposure developed PTLD at 1 year compared to no cases of PTLD among patients receiving pre-HSCT rituximab. There was no difference in neutrophil engraftment, incidence of infections, or aGVHD at day 180 between the 2 cohorts. There was a delay in time to platelet engraftment in the rituximab cohort (median 16 [IQR 15-20] days versus 15 [IQR 14-17] days; P = .04). Administration of pre-HSCT rituximab before allo-HSCT in patients receiving T-cell depletion with alemtuzumab was associated with a significant decrease in the risk for EBV reactivation and EBV-PTLD, without increasing aGVHD or infection rates.

The epidemiology and outcomes of prolonged trauma care (EpiC) study: methodology of a prospective multicenter observational study in the Western Cape of South Africa.

BACKGROUND: Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the "Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)" study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa. METHODS: The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient's clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure). DISCUSSION: This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system. TRIAL REGISTRATION: Not applicable as this study is not a clinical trial.

Optimizing Implementation of Preventive Chemotherapy against Soil-Transmitted Helminthiasis and Intestinal Schistosomiasis Using High-Resolution Data: Field-Based Experiences from Côte d'Ivoire.

BACKGROUND: Despite efforts to control neglected tropical diseases (NTDs) using preventive chemotherapy (PC), soil-transmitted helminthiases and schistosomiasis remain widely prevalent in sub-Saharan Africa. The current PC regimen in endemic settings is defined based on health district-level prevalence. This work aims to highlight the need for high-resolution data when elimination, rather than morbidity control, is the targeted goal. METHODOLOGY: Cross-sectional parasitological surveys were conducted from July to August 2019 and from September to October 2019, respectively, across the entire Dabou and Jacqueville health districts in southern Côte d'Ivoire. From every village, 60 school-aged children (6-15 years) were randomly selected and invited to provide one fresh stool sample, whereof duplicate Kato-Katz thick smears were prepared and read by two independent technicians. PRINCIPAL FINDINGS: 4338 school-aged children from 77 villages were screened from the Dabou (n = 2174; 50.12%, 39 villages) and Jacqueville (n = 2164; 49.88%, 38 villages) health districts. The prevalence of any soil-transmitted helminth (STH) infection was 12.47% and 11.09% in the Dabou and Jacqueville health districts, respectively. Species-specific district-level prevalence remained below 10%, varying between 0.51% (hookworm in Jacqueville) and 9.06% (Trichuris trichiura in Dabou). However, when considering sub-districts or villages only, several STH infection hotspots (five sub-districts with ≥20% and four villages with more than 50% infected) were observed. Schistosoma mansoni infection was found in less than 1% of the examined children in each health district. CONCLUSIONS/SIGNIFICANCE: We conclude that keeping health district-level prevalence as a reference for PC implementation leaves many high-risk sub-districts or villages requiring PC (≥20% prevalence) untreated. To avoid maintaining those high-risk villages as STH reservoirs by skipping control interventions and jeopardizing the successes already achieved in STH control through PC during the past two decades, precision mapping is required. Further investigation is needed to assess cost-efficient approaches to implement small-scale disease surveillance.

Biphasic Calcium Phosphate Versus Demineralized Freeze-Dried Bone Allograft in the Treatment of Periodontal Disease: A Clinical and Radiographical Evaluation.

 Aim The study aimed to clinically and radiographically evaluate the effect of biphasic calcium phosphate (BCP) versus demineralized freeze-dried bone allograft (DFDBA) in treating periodontal disease. Method The study consisted of 44 patients. The sites were randomly assigned to receive one of two treatment modalities (BCP at site 1 and demineralized freeze-dried bone at site 2) by a computerized method. All the clinical data were measured with the help of a University of North Carolina-15 (UNC-15) probe at the baseline, three months, and six months postoperatively. Radiovisiographs were taken using a Rinn XCP® (Dentsply/Rinn Corp, Elgin, IL) system and an oral grid using the paralleling technique. A manual calculation of the defect area was undertaken at the end of six months and was compared with the other groups. Result The linear bone growth recorded for site 1 at the end of six months was 3.8 ± 1.14 mm, and site 2 was 4.6 ± 1.07 mm. The intergroup comparison showed more remarkable linear bone growth in site 2, which was statistically insignificant, with a mean difference of 0.8 ± 1.23 mm and a p-value of 0.07. Conclusion Improvements were observed on all the documented parameters. However, the sites treated with DFDBA showed better periodontal regeneration.

Identifying Gingival Pigmentation Patterns and Skin Color and Its Co-relation With Serum Ferritin Levels in Thalassemic Patients.

BACKGROUND: Patients with ß-thalassemia major (ß-TM), a genetic issue due to hemoglobin (Hb) synthesis disorder, require life-long erythrocyte transfusion. The purpose of this study is to evaluate and compare gingival pigmentation and skin color with serum ferritin levels of patients with ß-TM, using the Dummett's oral pigmentation index (DOPI) and Fitzpatrick skin scale, respectively. METHODS: A total of 100 patients were monitored at a thalassemia care center. Each patient's gingival pigmentation and skin color were matched with DOPI and the skin scale under natural light. Serum ferritin levels, the interval of blood transfusions, and iron chelation medications were studied. A gingival pigmentation score and skin color type were compared with the serum ferritin. RESULTS: A significant correlation was found between age, serum ferritin, pigmentation score, and skin color, which means as serum ferritin level increases, gingival pigmentation score increases, and skin color darkens. CONCLUSION: This study evaluated the correlation between gingival pigmentation and skin color with serum ferritin levels and established gingival pigmentation as a sign of iron deposition in ß-TM patients. This is the simplest and least invasive method for evaluating serum ferritin level parameters in ß-TM patients.

The Role of Neuromodulation in Chronic Pelvic Pain: A Review Article.

BACKGROUND: Chronic pelvic pain (CPP) is a complex, heterogeneous condition affecting both female and male patients with significant effects on quality of life. Chronic pelvic pain is a prevalent but often underdiagnosed condition due to the variation in patient presentation, a gap in communication among specialties, under-reporting of the syndrome, and lack of standardized diagnostic criteria with a subsequent delay in diagnosis. The mechanism of CPP is complex due to multifactorial etiologies of pain and its vast anatomy and innervation. Potential causes of pelvic pain include the nerves, muscles, bone, or organs of the reproductive, gastrointestinal, urological, musculoskeletal, vascular, neurological, and psychological systems. OBJECTIVES: The objective of this article is to review the anatomy of the pelvis, share current lead placement locations, and discuss the current evidence for neuromodulation in the management of chronic pelvic pain. STUDY DESIGN: This is a narrative review of current literature on neuromodulation for chronic pelvic pain. SETTING: A database review. METHODS: A PubMed search was performed to gather literature on neuromodulation for chronic pelvic pain. RESULTS: Traditionally, pelvic pain has been managed with conservative therapies such as physical therapy, pharmacological agents, trigger point injections, botulinum toxin injections, ganglion impar blocks, caudal epidural steroid injections, or superior and inferior hypogastric blocks, but with the evolution of the neuromodulation, there are new advances to incorporate this modality in the management of chronic pelvic pain. LIMITATIONS: This review article possesses limitations and includes published data, excluding case reports. For this reason, some applications of neuromodulation for chronic pelvic pain may be missed. CONCLUSIONS: Neuromodulation may include spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. Specifically, neuromodulation utilizes electrical stimulation or pharmacological agents to modulate a nerve and alter pain signals. Currently used locations for lead placement include intracranial, spinal cord, dorsal root ganglion, sacral nerve roots, or at a peripheral nerve. As the field of pelvic pain continues to evolve, continued evidence for neuromodulatory interventions is needed.

Efficacy of drugs against clonorchiasis and opisthorchiasis: a systematic review and network meta-analysis.

BACKGROUND: Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three most important human liver fluke species in the Opisthorchiidae family, infecting approximately 25 million people worldwide. Drug treatment is needed to control morbidity and is also useful in lowering transmission. Several drugs used in various regimens are available to treat these infections, but their comparative efficacy is uncertain. We aimed to compare the efficacy in terms of cure rate and egg reduction rate of currently registered drugs against human liver fluke infection. METHODS: We conducted a systematic review using readily available electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, KoreaMed, China National Knowledge Infrastructure, and Wanfang Data) without language restrictions from inception until June 29, 2021. Clinical trials with pairwise comparison of drugs (praziquantel, albendazole, mebendazole, tribendimidine, or combinations of these drugs) against C sinensis, O viverrini, and O felineus were eligible, including trials comparing these drugs or their combinations with placebo. We compared efficacy in terms of cure rate by network meta-analysis. We conducted mixed binomial regression analyses for each species to derive predicted median cure rates for each drug regimen. The models included treatment and infection intensity as fixed factors, year of publication as covariate, and random effects of the different studies assumed to be normally distributed. We also assessed the quality of the included studies. This study was registered with PROSPERO (CRD42018109232). FINDINGS: Overall, 26 trials from 25 studies were included, of which 18 involved C sinensis, seven studied O viverrini, and one focused on O felineus. These trials included a total of 3340 participants. The two long-term treatment courses against C sinensis infection using 400 mg of albendazole (400 mg twice a day for 5 days and 400 mg twice a day for 7 days) resulted in cure rates of 100%, while two other multiple-dose regimens of albendazole resulted in high predicted cure rates: 300 mg twice a day for 5 days (93·9% [95% CI 49·6-99·6]) and 400 mg twice a day for 3 days (91·0% [50·9-99·0]). The WHO-recommended praziquantel regimen (25 mg/kg three times a day for 2 days) also showed a high predicted cure rate (98·5% [85·4-99·9]) in C sinensis infection, and predicted cure rates were above 90% for several other multiple-dose praziquantel regimens, including 20 mg/kg three times a day for 3 days (97·6% [74·7-99·8]), 14 mg/kg three times a day for 5 days (93·9% [44·8-99·7]), and 20 mg/kg twice a day for 3 days (91·0% [50·9-99·0]). In O viverrini infection, the regimen of 50 mg/kg and 25 mg/kg of praziquantel given in a single day showed the highest predicted cure rate (93·8% [85·7-97·5]), while a single dose of 50 mg/kg praziquantel also resulted in a high predicted cure rate (92·1% [64·9-98·6]). The single dose of 400 mg tribendimidine showed a high predicted cure rate of 89·8% (77·5-95·8). A low quality of evidence was demonstrated in most studies, especially those published before 2000. Selection bias due to poor random sequence generation and allocation concealment was high, and performance and detection biases were frequently unreported. INTERPRETATION: Praziquantel shows high efficacy against clonorchiasis and opisthorchiasis. Tribendimidine might serve as a treatment alternative and warrants further investigation. Although albendazole is efficacious when long treatment schedules (5 days or 7 days) are applied, limited size of studies and high risk of bias affect the interpretation of results. More high-quality studies are needed to promote the establishment of treatment guidelines for human liver fluke infection. FUNDING: Fourth Round of Three-Year Public Health Action Plan (2015-2017; Shanghai, China) and Swiss National Science Foundation.

Prolonged casualty care: Extrapolating civilian data to the military context.

BACKGROUND: Civilian and military populations alike are increasingly faced with undesirable situations in which prehospital and definitive care times will be delayed. The Western Cape of South Africa has some similarities in capabilities, injury profiles, resource limitations, and system configuration to US military prolonged casualty care (PCC) settings. This study provides an initial description of civilians in the Western Cape who experience PCC and compares the PCC and non-PCC populations. METHODS: We conducted a 6-month analysis of an ongoing, prospective, large-scale epidemiologic study of prolonged trauma care in the Western Cape (Epidemiology and Outcomes of Prolonged Trauma Care [EpiC]). We define PCC as ≥10 hours from injury to arrival at definitive care. We describe patient characteristics, critical interventions, key times, and outcomes as they may relate to military PCC and compare these using χ 2 and Wilcoxon tests. We estimated the associations between PCC status and the primary and secondary outcomes using logistic regression models. RESULTS: Of 995 patients, 146 experienced PCC. The PCC group, compared with non-PCC, were more critically injured (66% vs. 51%), received more critical interventions (36% vs. 29%), and had a greater proportionate mortality (5% vs. 3%), longer hospital stays (3 vs. 1 day), and higher Sequential Organ Failure Assessment scores (5 vs. 3). The odds of 7-day mortality and a Sequential Organ Failure Assessment score of ≥5 were 1.6 (odds ratio, 1.59; 95% confidence interval, 0.68-3.74) and 3.6 (odds ratio, 3.69; 95% confidence interval, 2.11-6.42) times higher, respectively, in PCC versus non-PCC patients. CONCLUSION: The EpiC study enrolled critically injured patients with PCC who received resuscitative interventions. Prolonged casualty care patients had worse outcomes than non-PCC. The EpiC study will be a useful platform to provide ongoing data for PCC relevant analyses, for future PCC-focused interventional studies, and to develop PCC protocols and algorithms. Findings will be relevant to the Western Cape, South Africa, other LMICs, and military populations experiencing prolonged care. LEVEL OF EVIDENCE: Therapeutic/care management; Level IV.