Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

Exploring malaria prediction models in Togo: a time series forecasting by health district and target group.

OBJECTIVES: Integrating malaria prediction models into malaria control strategies can help to anticipate the response to seasonal epidemics. This study aimed to explore the possibility of using routine malaria data and satellite-derived climate data to forecast malaria cases in Togo. METHODS: Generalised additive (mixed) models were developed to forecast the monthly number of malaria cases in 40 health districts and three target groups. Routinely collected malaria data from 2013 to 2016 and meteorological and vegetation data with a time lag of 1 or 2 months were used for model training, while the year 2017 was used for model testing. Two methods for selecting lagged meteorological and environmental variables were compared: a first method based on statistical approach ('SA') and a second method based on biological reasoning ('BR'). Both methods were applied to obtain a model per target group and health district and a mixed model per target group and health region with the health district as a random effect. The predictive skills of the four models were compared for each health district and target group. RESULTS: The most selected predictors in the models per district for the 'SA' method were the normalised difference vegetation index, minimum temperature and mean temperature. The 'SA' method provided the most accurate models for the training period, except for some health districts in children ≥5 years old and adults and in pregnant women. The most accurate models for the testing period varied by health district and target group, provided either by the 'SA' method or the 'BR' method. Despite the development of models with four different approaches, the number of malaria cases was inaccurately forecasted. CONCLUSIONS: These models cannot be used as such in malaria control activities in Togo. The use of finer spatial and temporal scales and non-environmental data could improve malaria prediction.

Marine Antimicrobial Peptides: An Emerging Nightmare to the Life-Threatening Pathogens.

The emergence of multidrug-resistant pathogens due to improper usage of conventional antibiotics has created a global health crisis. Alternatives to antibiotics being an urgent need, the scientific community is forced to search for new antimicrobials. This exploration has led to the discovery of antimicrobial peptides, a group of small peptides occurring in different phyla such as Porifera, Cnidaria, Annelida, Arthropoda, Mollusca, Echinodermata, and Chordata, as a component of their innate immune system. The marine environment, possessing immense diversity of organisms, is undoubtedly one of the richest sources of unique potential antimicrobial peptides. The distinctiveness of marine antimicrobial peptides lies in their broad-spectrum activity, mechanism of action, less cytotoxicity, and high stability, which form the benchmark for developing a potential therapeutic. This review aims to (1) synthesise the available information on the distinctive antimicrobial peptides discovered from marine organisms, particularly over the last decade, and (2) discuss the distinctiveness of marine antimicrobial peptides and their prospects.

Early switch to oral antibiotic therapy in patients with low-risk neutropenic sepsis (EASI-SWITCH): a randomized non-inferiority trial.

OBJECTIVES: To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. METHODS: This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12-24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. RESULTS: There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, -∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, -∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2-3] vs. 3 days [IQR 2-4]; p 0.002). DISCUSSION: Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population.

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

Dialectical Behavior Therapy in Juvenile Correctional and Detention Facilities: A Scoping Review.

Dialectical behavior therapy (DBT) has shown preliminary success in the treatment of youth in forensic settings. However, the implementation of DBT varies considerably from facility to facility. A scoping review was conducted to detail DBT intervention protocols in juvenile correctional and detention facilities. We described eight works' treatment setting, study design, youth characteristics, staff training, DBT approach, DBT skills modules, and main findings. All works involved DBT skills sessions, but few incorporated other DBT components such as individual therapy or skills coaching. Outcomes included reducing problematic behaviors such as aggression, improving mental health, and largely positive feedback regarding the DBT intervention from youth and staff. Our results consolidate the existing literature regarding DBT intervention in forensic settings for youth and inform future implementation and research of DBT in such facilities.

Preventing HIV Among Adolescent Boys and Young Men Through PEPFAR-Supported Voluntary Medical Male Circumcision in 15 Sub-Saharan African Countries, 2018-2021.

Voluntary medical male circumcision (VMMC) is an HIV prevention intervention that has predominantly targeted adolescent and young men, aged 10-24 years. In 2020, the age eligibility for VMMC shifted from 10 to 15 years of age. This report describes the VMMC client age distribution from 2018 to 2021, at the site, national, and regional levels, among 15 countries in southern and eastern Africa. Overall, in 2018 and 2019, the highest proportion of VMMCs were performed among 10-14-year-olds (45.6% and 41.2%, respectively). In 2020 and 2021, the 15-19-year age group accounted for the highest proportion (37.2% and 50.4%, respectively) of VMMCs performed across all age groups. Similarly, in 2021 at the site level, 68.1% of VMMC sites conducted the majority of circumcisions among men aged 15-24 years. This analysis highlights that adolescent boys and young men are the primary recipients of VMMC receiving an important lifetime reduction in HIV risk.

Disclosure of HIV status and adherence to antiretroviral treatment in children and adolescents from Lomé and Abidjan.

Introduction: in Africa, the proportion of minors with AIDS is ever increasing and adherence to treatment protocols is still suboptimal. The study investigated the conditions of HIV status disclosure and adherence to treatment in patients < 19 in two West African cities. Methods: in 2016, thirteen health professionals and four parents filled out questionnaires to identify problems and solutions relative to disclosure of HIV status and adherence to treatment in 208 children and adolescents seen at University Hospitals in Abidjan (Ivory Coast) and Lomé (Togo). Results: medians (extrema) of patients´ ages at start and end of status disclosure process were 10 (8-13) and 15 (13-17.5) years. In 61% of cases, disclosure was made individually after preparation sessions. The main difficulties were: parents´ disapproval, skipped visits, and rarity of psychologists. The solutions proposed were: recruiting more full-time psychologists, improving personnel training, and promoting patients´ "clubs". One out of three respondents was not satisfied with patients´ adherence to treatments. The major reasons were: intake frequencies, frequent omissions, school constraints, adverse effects, and lack of perceived effect. Nevertheless, 94% of the respondents confirmed the existence of support groups, interviews with psychologists, and home visits. To improve adherence, the respondents proposed increasing the number of support groups, sustaining reminder phone calls and home visits, and supporting therapeutic mentoring. Conclusion: despite persisting disclosure and adherence problems, appropriate measures already put into practice still need to be taken further, especially through engaging psychologists, training counsellors, and promoting therapeutic support groups.

3Rs implementation in veterinary vaccine batch-release testing: Current state-of-the-art and future opportunities. A webinar and workshop report.

Regulatory authorities require veterinary batch-release testing to confirm vaccine potency and safety, but these tests have traditionally relied on large numbers of laboratory animals. Advances in vaccine research and development offer increasing opportunities to replace in vivo testing, and some stakeholders have made significant progress in incorporating 3Rs elements in quality control strategies. A three-part event series entitled "3Rs Implementation in Veterinary Vaccine Batch-Release Testing: Current state-of-the-art and future opportunities" was jointly organized by the Animal-Free Safety Assessment Collaboration, HealthforAnimals, and the International Alliance of Biological Standardization. Two webinars and a workshop aimed to outline the state-of-the-art non-animal approaches for veterinary batch-release testing. The events included information on the state of the deletion of obsolete safety testing and the current initiatives implemented by European, North American, and Asian-Pacific stakeholders on 3Rs implementation and regulatory acceptance. The events contributed to a better understanding of the barriers to 3Rs implementation. Participants highlighted the need for open communication, continued collaboration between stakeholders, and international harmonization of regulatory requirements to help accelerate acceptance. Despite the challenges, the countries represented at this three-part event have shared their commitments to advancing the acceptance of alternative methods.

E-nursing homes: transforming access to nurses in nursing homes in response to the staffing crisis.

The UK is facing a nationwide staffing crisis within adult social care, due to difficulties in recruiting and retaining registered nurses. Current interpretation of legislation means nursing homes must always have the physical presence of a registered nurse on duty within the home. With the shortage of registered nurses increasing, reliance on agency workers is commonplace, a practice impacting service cost and continuity of care. Lack of innovation to tackle this issue means the question of how to transform service delivery to combat staffing shortages is open for debate. The potential for technology to augment the provision of care was highlighted during the COVID-19 pandemic. In this article the authors present one possible solution focused on the provision of digital nursing care within nursing homes. Anticipated benefits include enhanced accessibility of nursing roles, reduced risk of viral spread and opportunities for upskilling staff. However, challenges include the current interpretation of legislation.

Stem cell activation during distraction enterogenesis in the murine colon.

PURPOSE: Short bowel syndrome (SBS) is a devastating disease. We have proposed spring-mediated distraction enterogenesis for intestinal lengthening. Colonic lengthening is a potential treatment option for SBS to enhance fluid absorption capacity. We hypothesized that intraluminal spring-mediated colonic lengthening is associated with stem cell proliferation. METHODS: C57BL/6 mice underwent placement of a gelatin-encapsulated compressed or uncompressed nitinol spring in a cecal segment. Animals were given clear liquid diet until postoperative day (POD) 7, followed by regular diet until POD 14. Cecal lengths were measured at euthanasia, and tissue was formalin fixed for histological processing. For Lgr5-GFP mice, immunohistochemistry against GFP was performed to localize Lgr5+ cells within crypts. RESULTS: Significant cecal lengthening with compressed springs and shortening with uncompressed springs were observed on POD 7 and 14. Mucosa of the compressed spring group was significantly thicker on POD 14. The density of Lgr5+ cells within the crypts in the compressed spring groups was higher than that in the uncompressed spring groups on both POD 7 and 14. CONCLUSION: Expandable springs can be used to lengthen the colon in the mouse model. Colonic lengthening was associated with gradual mucosal thickening and correlated with an increased density of stem cells within the crypts.

Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.

Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 (KRASG12) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12 mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAF mutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (n = 800 patients) and found that KRASG12 mutations (n = 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P = 0.0031, adjusted interaction P = 0.015). For patients with KRASG12 mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (n = 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73-1.20; P = 0.85). In contrast, patients with KRASG13 mutant tumors showed significantly improved OS with FTD/TPI versus placebo (n = 60; HR = 0.29; 95% CI = 0.15-0.55; P < 0.001). In isogenic cell lines and patient-derived organoids, KRASG12 mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12 mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies.

SCOT: Tumor Sidedness and the Influence of Adjuvant Chemotherapy Duration on Disease Free Survival (DFS).

AIM: Patients with loco-regional right-sided colorectal tumors have a worse overall survival (OS). Here we investigate the difference in disease free survival (DFS) between colorectal patients with right and left sided tumors in the SCOT study. METHODS: The SCOT study showed 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) is non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. We divided the cohort into patients with left and right sided tumors, and evaluated the effect on DFS and the principle 3 versus 6-months analysis. RESULTS: 6088 patients with Stage III/high risk Stage II colorectal cancers were randomized between 27th March 2008 and 29th November 2013 from 244 centers internationally. In February 2017 (3-years FU) information on sidedness was available for 3309 patients (1238 R-sided, 2071 L-sided). Patients with right-sided tumors had a significantly worse DFS (3-year DFS right: 73.3% (se = 1.3%), left: 80.2% (se = 0.9%) HR 1.423 (95% CI 1.237-1.637; P < .0001). Adjusting for T and N-stage reduced the HR to 1.230 (95% CI 1.066-1.420, P = .005). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR 1.024 [0.831-1.261], L: HR 0.944 [0.783-1.139]). Test for heterogeneity, P = .571. Further sub-set analysis was limited due to cohort size. CONCLUSIONS: This is the first study to show that unselected patients with right-sided tumors had a worse DFS compared to left-sided tumors. Tumor sidedness did not impact upon the 3-months versus 6-months comparison in SCOT.

Using Bayesian Evidence Synthesis Methods to Incorporate Real-World Evidence in Surrogate Endpoint Evaluation.

OBJECTIVE: Traditionally, validation of surrogate endpoints has been carried out using randomized controlled trial (RCT) data. However, RCT data may be too limited to validate surrogate endpoints. In this article, we sought to improve the validation of surrogate endpoints with the inclusion of real-world evidence (RWE). METHODS: We use data from comparative RWE (cRWE) and single-arm RWE (sRWE) to supplement RCT evidence for the evaluation of progression-free survival (PFS) as a surrogate endpoint to overall survival (OS) in metastatic colorectal cancer (mCRC). Treatment effect estimates from RCTs, cRWE, and matched sRWE, comparing antiangiogenic treatments with chemotherapy, were used to inform surrogacy patterns and predictions of the treatment effect on OS from the treatment effect on PFS. RESULTS: Seven RCTs, 4 cRWE studies, and 2 matched sRWE studies were identified. The addition of RWE to RCTs reduced the uncertainty around the estimates of the parameters for the surrogate relationship. The addition of RWE to RCTs also improved the accuracy and precision of predictions of the treatment effect on OS obtained using data on the observed effect on PFS. CONCLUSION: The addition of RWE to RCT data improved the precision of the parameters describing the surrogate relationship between treatment effects on PFS and OS and the predicted clinical benefit of antiangiogenic therapies in mCRC. HIGHLIGHTS: Regulatory agencies increasingly rely on surrogate endpoints when making licensing decisions, and for the decisions to be robust, surrogate endpoints need to be validated. In the era of precision medicine, when surrogacy patterns may depend on the drug's mechanism of action and trials of targeted therapies may be small, data from randomized controlled trials may be limited.Real-world evidence (RWE) is increasingly used at different stages of the drug development process. When used to enhance the evidence base for surrogate endpoint evaluation, RWE can improve inferences about the strength of surrogate relationships and the precision of predicted treatment effect on the final clinical outcome based on the observed effect on the surrogate endpoint in a new trial.Careful selection of RWE is needed to reduce risk of bias.

Long-term safety of intraluminal spring-mediated bowel lengthening.

PURPOSE: The purpose of the study is to examine the long-term safety of an endoluminal bowel lengthening device prior to its use in the first human trial. In addition, device performance and natural passage will be evaluated. METHODS: Endoluminal lengthening springs were surgically placed into the jejunum of Yucatan minipigs using the Eclipse XL1 device. A matching internal control segment of jejunum was marked at the time of operation. Weekly weights and fluoroscopic studies were obtained to evaluate spring deployment and position until devices passed. Animals were euthanized at 28, 60, 90, and 180 days. At necropsy, length measurements were recorded, and histopathologic analysis was performed. RESULTS: There were no bowel obstructions or overt perforations attributable to the device. All surviving animals gained weight and were clinically thriving. All devices passed out of the rectum by 180 days. Bowel lengthening was seen in all experimental segments, and minimal fibrosis was observed by 180 days. CONCLUSION: Jejunal lengthening persisted after device had passed through the intestinal tract after 180 days. Early histopathologic changes of the jejunum during distraction enterogenesis normalized over time.

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer. METHODS: Studies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English. RESULTS: Thirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49-10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type. DISCUSSION: Here we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical. PROTOCOL REGISTRATION: The protocol for this review is registered on PROSPERO (CRD42021261569).

Effectiveness of seasonal malaria chemoprevention in three regions of Togo: a population-based longitudinal study from 2013 to 2020.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended seasonal malaria chemoprevention (SMC) in areas of high seasonal transmission. Though implemented since 2013, the effectiveness of SMC in Togo was never evaluated. METHODS: This study concerned routine data from 2013 to 2020 mass SMC campaigns for children under five in all health facilities of three Regions of Togo. Treatment coverage, reasons for non-treatment, and SMC-attributable adverse reactions were analysed per year and treatment round. Random effect logistic models estimated SMC effectiveness per health district, year, and treatment round. RESULTS: The overall coverage was 98% (7,971,877 doses for 8,129,668 children). Contraindication was the main reason for non-administration. Over the study period, confirmed malaria cases decreased from 11,269 (1st round of 2016) to 1395 (4th round of 2020). Only 2,398 adverse reactions were reported (prevalence: 3/10,000), but no severe Lyell syndrome or Stevens-Johnson-type skin reaction. Compared to 2016, malaria prevalence decrease was estimated at 22.6% in 2017 (p < 0.001) and 75% in 2020 (p < 0.001). SMC effectiveness ranged from 76.6% (2nd round) to 96.2% (4th round) comparison with the 1st round. CONCLUSIONS: SMC reduced significantly malaria cases among children under five. The results reassure all actors and call for effort intensification to reach the WHO goals for 2030.

Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020.

Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic.

The effect of spring diameter on porcine ileal distraction enterogenesis.

PURPOSE: Spring-mediated distraction enterogenesis has proven to be successful for intestinal lengthening. We aimed to evaluate the effect of spring diameter mismatch on intestinal adaptation. METHODS: Juvenile mini-Yucatan pigs underwent placement of compressed nitinol springs with diameter of 10, 11, or 12 mm into the ileal lumen. Pigs were euthanized on postoperative day 7. The lengths, histology, total area of blood vessels, and enteric ganglia were evaluated. RESULTS: All spring groups exhibited significant ileal lengthening. Across the different diameters, spring-expanded segments were similar in terms of ileal lengthening, crypt height, muscular thickness, blood vessels, and enteric ganglia area. CONCLUSION: Spring-mediated distraction enterogenesis is successful in the porcine ileum. A smaller diameter spring is as effective as a larger diameter spring in lengthening the ileum. Springs of varying diameters result in comparable structural changes in the ileum.