NSAIDs do not reduce severity among post-ERCP pancreatitis patients.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most studied chemoprophylaxis for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). While previous systematic reviews have shown NSAIDs reduce PEP, their impact on moderate to severe PEP (MSPEP) is unclear. We conducted a systematic review and meta-analysis to understand the impact of NSAIDs on MSPEP among patients who developed PEP. We later surveyed physicians' understanding of that impact. DESIGN: A systematic search for randomized trials using NSAIDs for PEP prevention was conducted. Pooled-prevalence and Odds-ratio of PEP, MSPEP were compared between treated vs. control groups. Analysis was performed using R software. Random-effects model was used for all variables. Physicians were surveyed via email before and after reviewing our results. RESULTS: 7688 patients in 25 trials were included. PEP was significantly reduced to 0.598 (95%CI, 0.47-0.76) in the NSAIDs group. Overall burden of MSPEP was reduced among all patients undergoing ERCP: OR 0.59 (95%CI, 0.42-0.83). However, NSAIDs didn't affect the proportion of MSPEP among those who developed PEP (p = 0.658). Rectal Indomethacin and diclofenac reduced PEP but not MSPEP. Efficacy didn't vary by risk, timing of administration, or bias-risk. Survey revealed a change in the impression of the effect of NSAIDs on MSPEP after reviewing our results. CONCLUSIONS: Rectal diclofenac or indomethacin before or after ERCP reduce the overall burden of MSPEP by reducing the pool of PEP from which it can arise. However, the proportion of MSPEP among patients who developed PEP is unaffected. Therefore, NSAIDs prevent initiation of PEP, but do not affect severity among those that develop PEP. Alternative modalities are needed to reduce MSPEP among patients who develop PEP.

An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP).

BACKGROUND: Although rectal administration of nonsteroidal anti-inflammatory drugs is recommended as the standard pharmacologic modality to prevent postendoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP), vigorous periprocedural hydration (vHR) with lactated Ringer's solution (LR) is emerging as an effective prophylaxis modality for PEP. There has been no head-to-head comparison between these 2. STUDY: This was a single-center, randomized, open-label, noninferiority, parallel-assigned, equal allocation, controlled clinical trial in a tertiary care hospital. Consecutive adults referred for ERCP, satisfying predefined inclusion criteria, underwent simple randomization and blinded allocation into 2 groups. Those allocated to vHR received intravenous LR at 3 mL/kg/h during procedure, 20 ml/kg bolus immediately afterward, and then at 3 mL/kg/h for another 8 hours. Those randomized to rectal Indomethacin received only per-rectal 100 mg suppository immediately post-ERCP. Assuming PEP of 9% in Indomethacin arm and noninferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5%. Primary outcome was incidence of PEP, within 1 week, as defined by Cotton's criteria. All analysis were done by intention-to-treat. RESULTS: Between October, 2017 to February, 2018, 521 patients were assessed. In all, 352 were enrolled, 178 randomized to vHR, and 174 to per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between 2 groups. PEP occurred in 6 (1.7%) overall, with 1 (0.6%) in hydration arm, and 5 (2.9%) in indomethacin arm; an absolute risk reduction of 2.3% (95% confidence interval: 0.9%-3.5%) and odds ratio of 0.19 (95% confidence interval: 0.02-1.65). Three patients developed severe PEP, all receiving indomethacin. CONCLUSIONS: vHR with LR is noninferior to postprocedure per-rectal Indomethacin for PEP prevention (ClinicalTrials.govID:NCT03629600).

Combination Topical Epinephrine and Non-steroidal Inflammatory Drugs in the Prevention of Post-ERCP Pancreatitis: A Systematic Review.

BACKGROUND: The utility of combination rectal NSAID and topical epinephrine (EI) or rectal NSAID and normal saline (SI) sprayed on duodenal papilla in the prevention of post-ERCP pancreatitis (PEP) has been studied but results have been conflicting. AIMS: To evaluate the benefit of using combination prophylaxis in preventing PEP. METHODS: A literature search was performed using Scopus, PubMed/MEDLINE, and Cochrane databases in May 2021. Randomized controlled trials (RCTs) involving adults patients who underwent ERCP and received EI versus SI were eligible for inclusion. The pooled effect was expressed as odds ratio (OR) to assess the rate of PEP, severity of PEP, and specific adverse events. The results were pooled using Reviewer Manager 5.4 software. RESULTS: Six RCTs involving 4016 patients were included in the final analysis. The EI group did not demonstrate any significant benefit over SI group in preventing PEP (OR = 1.00, 95% CI [0.68, 1.45], P = 0.98), irrespective of gender or the epinephrine concentration used. The tests for subgroup differences were not statistically significant with P-values of 0.66 and 0.28, respectively. The addition of topical epinephrine to rectal NSAID did not improve the rate of moderate to severe PEP (OR = 0.94, P = 0.86) or PEP in high-risk patients (OR = 1.14, 95%, P = 0.73). The rates of infection, including cholangitis and sepsis (OR = 0.63, P = 0.07), gastrointestinal bleeding (OR = 1.25, P = 0.56) and procedure-related death (OR = 0.71, P = 0.59) were similar between both groups. CONCLUSION: The addition of topical epinephrine did not demonstrate any benefit over rectal NSAID alone in preventing PEP or reducing other procedure-related adverse events.

A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States.

BACKGROUND & AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. METHODS: We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). RESULTS: Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). CONCLUSIONS: Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. METHODS: We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. RESULTS: The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. CONCLUSIONS: Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.

Emerging Therapies to Prevent Post-ERCP Pancreatitis.

PURPOSE OF REVIEW: The aim of this review is to evaluate emerging, novel therapies for the prevention of post-ERCP pancreatitis. RECENT FINDINGS: Rectal indomethacin reduces the risk of pancreatitis in low- and average-risk patients, who comprise the majority of patients undergoing ERCP. An 8-h protocol of aggressive lactated Ringer's reduces the risk of pancreatitis in average-risk patients. Sublingual nitrate may provide additional benefit to rectal NSAIDs in preventing PEP. A tacrolimus trough > 2.5 ng/mL was recently shown to be associated with a lower risk of PEP in liver transplant patients undergoing ERCP. Routine usage of rectal indomethacin in all patients undergoing ERCP reduces the risk of PEP. Pancreatic-duct stents reduce the risk of PEP in high-risk patients. There is emerging data that aggressive hydration with lactated Ringer's and nitrates may further reduce PEP. Tacrolimus is a promising potential agent to prevent PEP but needs further clinical study.

Adherence to the referral advice after introduction of rectal artesunate for pre-referral treatment of severe malaria at the community level: a noninferiority trial in the Democratic Republic of the Congo.

BACKGROUND: The Democratic Republic of the Congo adopted the strategy of using, at the community level, a dose of rectal artesunate as a pre-referral treatment for severe malaria amongst children under 5 years who could not quickly reach a health care facility and take oral medication. However, the adherence to referral advice after the integration of this strategy and the acceptability of the strategy were unknown. METHODS: To assess adherence by the mothers/caretakers of children under 5 years to referral advice provided by the community health workers after pre-referral treatment of severe malaria with rectal artesunate, the authors conducted a noninferiority community trial with a pre- and post-intervention design in 63 (pre-intervention) and 51 (post-intervention) community care sites in 4 provinces (Kasaï-Oriental, Kasaï-Central, Lomami, Lualaba) from August 2014 through June 2016. The pre- and post-intervention surveys targets 387 mothers of children under 5 years and 63 community health workers and 346 mothers and 41 community health workers, respectively. A 15% margin was considered for noninferiority analyses due to the expected decrease in adherence to referral advice after the introduction of the new intervention. RESULTS: The mothers acknowledged that the rectal route was often used (60.7%), and medicines given rectally were considered more effective (63.6%) and easy to administer (69.7%). The acceptability of pre-referral rectal artesunate was relatively high: 79.4% (95% CI 75.4-83.3) among mothers, 90.3% (95% CI 82.3-96.8) among community health workers, and 97.8% (95% CI 93.3-100) among nurses. Adherence to referral advice at post-intervention [84.3% (95% CI 80.6-88.1)] was non-inferior to pre-intervention adherence [94.1% (95% CI 91.7-96.4)]. CONCLUSIONS: The integration of pre-referral rectal artesunate for severe malaria into the community care site in the DR Congo is feasible and acceptable. It positively affected adherence to referral advice. However, more health education is needed for parents of children under 5 years and community health workers.

Household costs and time to treatment for children with severe febrile illness in rural Burkina Faso: the role of rectal artesunate.

BACKGROUND: Community health workers (CHWs) were trained to identify children with malaria who could not take oral medication, treat them with rectal artesunate (RA) and refer them to the closest healthcare facility to complete management. However, many children with such symptoms did not seek CHWs' care. The hypothesis was that the cost of referral to a health facility was a deterrent. The goal of this study was to compare the out-of-pocket costs and time to seek treatment for children who sought CHW care (and received RA) versus those who did not. METHODS: Children with symptoms of severe malaria receiving RA at CHWs and children with comparable disease symptoms who did not go to a CHW were identified and their parents were interviewed. Household out-of-pocket costs per illness episode and speed of treatment were evaluated and compared between RA-treated children vs. non-RA treated children and by central nervous symptoms (CNS: repeated convulsions, altered consciousness or coma). RESULTS: Among children with CNS symptoms, costs of RA-treated children were similar to those of non-RA treated children ($5.83 vs. $4.65; p = 0.52), despite higher transport costs ($2.74 vs. $0.91; p < 0.0001). However, among children without CNS symptoms, costs of RA-treated children were higher than the costs of non-RA treated children with similar symptoms ($5.62 vs. $2.59; p = 0.0001), and the main driver of the cost difference was transport. After illness onset, CNS children reached CHWs for RA an average of 9.0 h vs. 16.1 h for non-RA treated children reaching first treatment [difference 7.1 h (95% CI - 1.8 to 16.1), p = 0.11]. For non-CNS patients the average time to CHW-delivered RA treatment was 12.2 h vs. 20.1 h for those reaching first treatment [difference 7.9 h (95% CI 0.2-15.6), p = 0.04]. More non-RA treated children developed CNS symptoms before arrival at the health centre but the difference was not statistically significant (6% vs. 4%; p = 0.58). CONCLUSIONS: Community health worker-delivered RA does not affect the total out-of-pocket costs when used in children with CNS symptoms, but is associated with higher total out-of-pocket costs when used in children with less severe symptoms. RA-treated children sought treatment more quickly.

Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men.

Oral pre-exposure prophylaxis (PrEP) can prevent HIV transmission. Yet, some may prefer not to take systemic daily medication. MTN-017 was a 3-period, phase 2 safety and acceptability study of microbicide gel applied rectally either daily or before and after receptive anal intercourse (RAI), compared to daily oral tablet. At baseline, cisgender men and transgender women who reported RAI (N = 187) rated the daily oral regimen higher in overall liking, ease of use, and likelihood of future use than the gel regimens. After trying all three, 28% liked daily oral the least. Gel did not affect sexual enjoyment (88%) or improved it (7-8%). Most partners had no reaction to gel use. Ease of gel use improved significantly between the first and the last few times of daily use. A rectal gel used before and after RAI may constitute an attractive alternative to daily tablet. Experience with product use may increase acceptability.

Rectal NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in unselected patients: Systematic review and meta-analysis.

BACKGROUND AND AIM: Efficacy of rectal non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prophylaxis in unselected patients remained controversial. The aim of the present study was to evaluate the efficacy of rectal NSAIDs in the prevention of PEP in unselected patients. METHODS: An electronic literature search in the Cochrane Library, Embase, and PubMed was carried out for randomized controlled trials comparing rectal indomethacin or diclofenac with placebo in the prevention of PEP in unselected patients. Cochrane risk of bias tool was used to evaluate methodological quality. The data were carried out in forest plots using fixed-effect methods, and random-effect methods were used when heterogeneity was significant. RESULTS: A total of nine trials were included in our final analysis. Rectal NSAIDs were effective to reduce the incidence of PEP in unselected patients (RR, 0.61; 95% CI, 0.46-0.79), especially for moderate-to-severe PEP (RR, 0.37; 95% CI, 0.17-0.79). Both indomethacin (RR, 0.67; 95% CI, 0.50-0.88) and diclofenac (RR, 0.29; 95% CI, 0.12-0.69) were significantly efficacious. Rectal NSAIDs given pre-ERCP showed significant efficacy (RR, 0.53; 95% CI, 0.39-0.71), whether when given within 30 min pre-ERCP (RR, 0.62; 95% CI, 0.42-0.92) or not (RR, 0.43; 95% CI, 0.28-0.67). CONCLUSION: Rectal NSAIDs are effective in the prevention of PEP in unselected patients.

Curative effect of Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease.

This paper aims to analyze the curative effect of Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease. 97 patients with chronic pelvic inflammatory disease admitted to our hospital from June 2015 to June 2016 were selected and randomly divided into observation group and control group. Patients in control group were treated with Kangfuxiaoyan suppository and patients in the observation group were treated with Jin'gangteng capsule combined with kangfuxiaoyan suppository treatment. The curative effect between the two groups was compared. The scores of symptoms and signs in the observation group after treatment were lower than those in the control group. The total effective rate of the observation group was higher than that of the control group, and there was significant difference between the two groups, P<0.05. Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease can improve the treatment efficiency and promote the rapid and effective relief of clinical symptoms and signs.

Compliance With Malaria Rapid Diagnostic Testing by Community Health Workers in 3 Malaria-Endemic Countries of Sub-Saharan Africa: An Observational Study.

BACKGROUND: The World Health Organization recommends that all malaria management be based on parasitological identification. We monitored performance of trained community health workers (CHWs) in adhering to this recommendation to restrict artemisinin-based combination therapies (ACTs) to positive rapid diagnostic test (RDT)-confirmed cases in children in 3 malaria-endemic sub-Saharan African countries. METHODS: In 33 villages in Burkina Faso, 45 villages in Nigeria, and 84 villages in Uganda, 265 CHWs were trained over a minimum of 3 days to diagnose malaria using RDTs (prepare, read, record results, and inform the patient about results) and treat RDT-confirmed uncomplicated malaria cases with ACTs. In Nigeria, CHWs were also taught to obtain a thick blood smear. Spent RDT kits and prepared blood slides were collected and interpreted independently in Burkina Faso and Nigeria to confirm CHWs' diagnoses. Interviews were held with 12 of 17 CHWs who prescribed ACTs for patients with RDT-negative test results, and with 16 of 29 caregivers to determine factors related to noncompliance. RESULTS: Of 12 656 patients treated with ACTs in the participating countries (5365 in Burkina Faso, 1648 in Nigeria, and 5643 in Uganda), 29 patients (8 from Burkina Faso, 17 from Nigeria, 4 from Uganda) were RDT negative. The small number of RDT-negative ACT-treated cases limits statistical analysis. Only a few CHWs were involved, and they were more likely to be traders rather than farmers (odds ratio [OR], 6.15; 95% confidence interval [CI], 2.09-18.07; P = .0004). RDT-negative children who were treated with ACTs had a significantly higher probability of residing in a village other than that of the CHW (OR, 3.85; 95% CI, 1.59-9.30; P = .0018). Parental pressure was identified in interviews with parents. CONCLUSIONS: Noncompliance with results of RDT tests is relatively rare when CHWs are trained and well supervised. CLINICAL TRIALS REGISTRATION: ISRCTN13858170.

Training Community Health Workers to Manage Uncomplicated and Severe Malaria: Experience From 3 Rural Malaria-Endemic Areas in Sub-Saharan Africa.

BACKGROUND: Use of community health workers (CHWs) to increase access to diagnosis and treatment of malaria is recommended by the World Health Organization. The present article reports on training and performance of CHWs in applying these recommendations. METHODS: Two hundred seventy-nine CHWs were trained for 3-5 days in Burkina Faso, Nigeria, and Uganda, and 19 were certified to diagnose and treat only uncomplicated malaria and 235 to diagnose and treat both uncomplicated and severe malaria. Almost 1 year after training, 220 CHWs were assessed using standard checklists using facility staff responses as the reference standard. RESULTS: Training models were slightly different in the 3 countries, but the same topics were covered. The main challenges noticed were the low level of education in rural areas and the involvement of health staff in the supervision process. Overall performance was 98% (with 99% in taking history, 95% in measuring temperature, 85% for measuring respiratory rates, 98% for diagnosis, 98% for classification, and 99% for prescribing treatment). Young, single, new CHWs performed better than their older, married, more experienced counterparts. CONCLUSIONS: Training CHWs for community-based diagnosis and treatment of uncomplicated and severe malaria is possible with basic and refresher training and close supervision of CHWs' performance. CLINICAL TRIALS REGISTRATION: ISRCTRS13858170.

Compliance With Referral Advice After Treatment With Prereferral Rectal Artesunate: A Study in 3 Sub-Saharan African Countries.

BACKGROUND: Children aged <5 years were enrolled in a large study in 3 countries of sub-Saharan Africa because they had danger signs preventing them from being able to take oral medications. We examined compliance and factors associated with compliance with referral advice for those who were treated with rectal artesunate. METHODS: Patient demographic data, speed of accessing treatment after danger signs were recognized, clinical symptoms, malaria microscopy, treatment-seeking behavior, and compliance with referral advice were obtained from case record forms of 179 children treated with prereferral rectal artesunate in a multicountry study. We held focus group discussions and key informant interviews with parents, community health workers (CHWs), and facility staff to understand the factors that deterred or facilitated compliance with referral advice. RESULTS: There was a very high level of compliance (90%) among patients treated with prereferral rectal artesunate. Age, symptoms at baseline (prostration, impaired consciousness, convulsions, coma), and malaria status were not related to referral compliance in the analysis. CONCLUSIONS: Teaching CHWs to diagnose and treat young children with prereferral rectal artesunate is feasible in remote communities of Africa, and high compliance with referral advice can be achieved.

Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial.

BACKGROUND: If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS: Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS: Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS: Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION: ISRCTN58046240.

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Pre-referral rectal artesunate for severe malaria.

BACKGROUND: Severe or complicated malaria is a medical emergency and people die as a result of delays in starting treatment. Most patients need parenteral treatment, and in primary healthcare facilities, where intravenous therapy is not available but intramuscular injections can be given, intramuscular quinine, artesunate, and artemether have been used before transporting patients to hospital.However, in rural settings with limited access to health care, intramuscular injections may also be unavailable. In these situations, rectal artesunate given prior to transfer to hospital by volunteers with little medical training, may be a feasible option. OBJECTIVES: To evaluate the effects of pre-referral treatment with rectal artesunate on mortality and morbidity in people with severe malaria. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE and LILACS up to 21 May 2014. We also searched the WHO clinical trial registry platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials. SELECTION CRITERIA: Individual or cluster-randomized controlled trials comparing pre-referral rectal artesunate with placebo or injectable antimalarials in children and children with severe malaria. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for potentially eligible trials, and extracted data from the included trials. Dichotomous outcomes were summarized using risk ratios (RR) and presented with 95% confidence intervals (95% CI). Where data allowed, we conducted subgroup analyses by age, trial region and whether participants were included in the trial analysis. We assessed the quality of evidence for the most important outcomes using the GRADE approach. MAIN RESULTS: One trial met the inclusion criteria; a placebo-controlled trial of 17,826 children and adults living in rural villages in Ghana and Tanzania (Africa) and Bangladesh (Asia). Villagers with no previous medical training were trained to recognize the symptoms of severe malaria, administer rectal artesunate and refer patients to hospital. The trained villagers were supervised during the trial period. In the African sites only children aged 6 to 72 months were enrolled, whereas in Bangladesh, older children and adults were also enrolled.In young children (aged 6 to 72 months) there were fewer deaths following rectal artesunate than with placebo (RR 0.74; 95% CI 0.59 to 0.93; one trial; 8050 participants; moderate quality evidence), while in older children and adults there were more deaths in those given rectal artesunate (RR 2.21; 95% CI 1.18 to 4.15; one trial; 4018 participants; low quality evidence).In Africa, only 56% of participants reached a secondary healthcare facility within six hours compared to over 90% in Asia. There were no differences between the intervention and control groups in the proportion of participants reaching a healthcare facility within six hours (RR 0.99; 95% CI 0.98 to 1.01; 12,068 participants), or in the proportion with parasitaemia (RR 1.00; 95% CI 0.98 to 1.02; 17,826 participants), or with coma or convulsions on arrival (RR 1.01; 95% CI 0.90 to 1.14; 12,068 participants).There are no existing trials that compare rectal versus intramuscular artesunate. AUTHORS' CONCLUSIONS: In rural areas without access to injectable antimalarials rectal artesunate provided before transfer to a referral facility probably reduces mortality in severely ill young children compared to referral without treatment. However, the unexpected finding of possible higher mortality in older children and adults has to be taken into account in forming any national or local policies about pre-referral rectal artesunate.

Rectal nonsteroidal anti-inflammatory drugs are superior to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a network meta-analysis.

BACKGROUND & AIMS: Placement of pancreatic duct (PD) stents prevents pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). There is evidence that rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) also prevents post-ERCP pancreatitis, but the 2 approaches alone have not been compared directly. We conducted a network meta-analysis to indirectly compare the efficacies of these procedures. METHODS: PubMed and Embase were searched by 2 independent reviewers to identify full-length clinical studies, published in English, investigating use of PD stent placement and rectal NSAIDs to prevent post-ERCP pancreatitis. We identified 29 studies (22 of PD stents and 7 of NSAIDs). We used network meta-analysis to compare rates of post-ERCP pancreatitis among patients who received only rectal NSAIDs, only PD stents, or both. RESULTS: Placement of PD stents and rectal administration of NSAIDs were each superior to placebo in preventing post-ERCP pancreatitis. The combination of rectal NSAIDs and stents was not superior to either approach alone. Pooled results showed that rectal NSAIDs alone were superior to PD stents alone in preventing post-ERCP pancreatitis (odds ratio, 0.48; 95% confidence interval, 0.26-0.87). CONCLUSIONS: Based on a network meta-analysis, rectal NSAIDs alone are superior to PD stents alone in preventing post-ERCP pancreatitis, and should be considered first-line therapy for selected patients. However, these findings were limited by the small number of studies assessed (only 29 studies), potential publication bias, and the indirect nature of the comparison. High-quality, randomized, controlled trials are needed to compare these 2 interventions and confirm these findings.

Randomized clinical trial of subcutaneous versus interfascial bupivacaine for pain control after midline laparotomy.

BACKGROUND: Although patient-controlled analgesia for pain management after abdominal surgery is common, efforts to find alternative effective methods to control postoperative pain are continuing. The aim of this study was to compare postoperative pain levels following intermittent regional administration of bupivacaine via a catheter placed in the rectus sheath or subcutaneously at abdominal surgery through midline incisions. METHODS: Consecutive patients undergoing elective midline laparotomy were assigned randomly to a group with two catheters placed over the fascia (suprafascial group) before surgical wound closure or to a group with catheters placed between the two sheaths of each rectus muscle (interfascial group). Pain levels were determined every 12 h, both at rest and with movement, by means of a standard visual analogue scale (VAS) for 72 h after surgery. The amounts of administered opioid were recorded. RESULTS: Sixty patients were enrolled in the study (30 patients in each group).The median VAS score 36 h after surgery, both at rest and with movement, was significantly lower in the interfascial group than in the suprafascial group (P<0·050). Repeated-measures ANOVA also showed a significant difference in the postoperative VAS scores (P<0·007). The amount of self-administered morphine was significantly lower in the interfascial group, overall (P = 0·001) as well as on postoperative day 1 (P = 0·001) and day 2 (P = 0·016). Bowel sounds returned more quickly in the interfascial group (P = 0·040). CONCLUSION: Locoregional catheter administration of bupivacaine following midline laparotomy is more effective when the catheter is placed in the rectus sheath compared with suprafascial delivery. REGISTRATION NUMBER: IRCT138810142982N1 (http://www.irct.ir).