Non-adherence to ivermectin in onchocerciasis-endemic communities with persistent infection in the Bono Region of Ghana: a mixed-methods study.

BACKGROUND: The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection. METHODS: In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged ≥ 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted. RESULTS: A total of 510 people participated in the study [median age: 32, interquartile range 30 (20‒50) years]; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake. CONCLUSIONS: A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.

Standardised Competency-Based Training of Medical Doctors and Associate Clinicians in Inguinal Repair with Mesh in Sierra Leone.

INTRODUCTION: In low-income settings, there is a high unmet need for hernia surgery, and most procedures are performed with tissue repair techniques. In preparation for a randomized clinical trial, medical doctors and associate clinicians received a short-course competency-based training on inguinal hernia repair with mesh under local anaesthesia. The aim of this study was to evaluate feasibility, safety and effectiveness of the training. METHODS: All trainees received a one-day theoretical module on mesh hernia repair under local anaesthesia followed by hands-on training. Performance was assessed using the American College of Surgeon's Groin Hernia Operative Performance Rating System. Patients were followed up two weeks and one year after surgery. Outcomes of the patients operated on during the training trial were compared to the 229 trial patients operated on after the training. RESULTS: During three surgical camps, seven medical doctors and six associate clinicians were trained. In total, 129 patients were operated on as part of the training. Of the 13 trainees, 11 reached proficiency. Patients in the training group had more wound infections after two weeks (8.5% versus 3.1%; p = 0.041). There was no difference in recurrence and mortality after one year, and none of the deaths were attributed to the surgery. DISCUSSION AND CONCLUSION: Mesh repair is the international standard for inguinal hernia repair worldwide. Nevertheless, this is not widely accessible in low-income settings. This study has demonstrated that short-course intensive hands-on training of MDs and ACs in mesh hernia repair is effective and safe. TRIAL REGISTRATION: International Clinical Trial Registry ISRCTN63478884.

Language-to-music transfer effects depend on the tone language: Akan vs. East Asian tone languages.

Recent research suggests that speaking a tone language confers benefits in processing pitch in nonlinguistic contexts such as music. This research largely compares speakers of nontone European languages (English, French) with speakers of tone languages in East Asia (Mandarin, Cantonese, Vietnamese, Thai). However, tone languages exist on multiple continents-notably, languages indigenous to Africa and the Americas. With one exception (Bradley, Psychomusicology, 26(4), 337-345, 2016), no research has assessed whether these tone languages also confer pitch processing advantages. Two studies presented a melody change detection task, using quasirandom note sequences drawn from Western major scale tone probabilities. Listeners were speakers of Akan, a tone language of Ghana, plus speakers from previously tested populations (nontone language speakers and East Asian tone language speakers). In both cases, East Asian tone language speakers showed the strongest musical pitch processing, but Akan speakers did not exceed nontone speakers, despite comparable or better instrument change detection. Results suggest more nuanced effects of tone languages on pitch processing. Greater numbers of tones, presence of contour tones in a language's tone inventory, or possibly greater functional load of tone may be more likely to confer pitch processing benefits than mere presence of tone contrasts.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Pregnancy in Sub-Saharan Africa: A 6-Country Retrospective Cohort Analysis.

BACKGROUND: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. RESULTS: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13). CONCLUSIONS: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.

"Once you get one maternal death, it's like the whole world is dropping on you": experiences of managing maternal mortality amongst obstetric care providers in Ghana.

BACKGROUND: Maternal mortality has a significant global impact, especially in low-resource settings. Little prior research has been conducted on the potential effects of poor maternal outcomes on the personal and professional well-being of healthcare providers. This study explores the in-depth experiences and perspectives of obstetric providers in Ghana who work in a setting with frequent maternal mortalities. METHODS: This is a qualitative study of semi-structured interviews conducted at the Komfo Anokye Teaching Hospital in Ghana. Participants were obstetric healthcare providers, defined as midwives, house officers currently rotating on the obstetrics/gynecology service, and obstetrician/gynecologists at any training or practice level (residents, fellows, and specialists). Interviews were audio-recorded, transcribed verbatim, and uploaded into NVivo for qualitative analysis. Using the Attride-Stirling qualitative model, an incremental and iterative process was used to code interviews with keyword phrases and develop a framework of organizing and global themes. RESULTS: Interviews were conducted with 27 participants-15 midwives and 12 physicians (three obstetrician/gynecologist residents, six obstetrician/gynecologist specialists, and three house officers), with sample size determined by data saturation. Obstetric providers' experiences in a setting with frequent maternal mortalities were dependent on their level of preparedness to manage maternal mortalities and the workplace environment. Providers' level of preparedness was dependent on both the training they had received on the medical management of obstetric emergencies, as well as a lack of training on the mental health aspects of coping with maternal mortality. The impact of the workplace environment was dependent on systems failures and limited resources, blame from colleagues and supervisors, and a lack of support in the workplace. In turn, obstetric providers' experiences managing frequent maternal mortalities impacted their clinical care performance and mental health. CONCLUSIONS: Maternal deaths have profound personal and professional impacts on the healthcare providers who manage them. A large need exists for additional institutional training and support for obstetric providers who manage maternal mortality, especially in low-resource settings like Ghana.

Dual soluble epoxide hydrolase inhibitor/PPAR-γ agonist attenuates renal fibrosis.

Renal fibrosis is a contributor to chronic kidney disease and an important predictor of long-term prognosis. We developed a dual soluble epoxide hydrolase inhibitor-PPAR-γ agonist (sEHi/PPAR-γ), RB394, and investigated its ability to attenuate renal fibrosis in a mouse unilateral ureteral obstruction (UUO) model. RB394 efficacy was compared to an sEH inhibitor (sEHi), a PPAR-γ agonist rosiglitazone (Rosi), or their combination (sEHi + Rosi). All interventional treatments were administrated in drinking water 3 days after UUO induction surgery and continued for 7 days. UUO mice developed renal fibrosis with higher collagen formation and RB394 significantly attenuated fibrosis (P < 0.05). Renal expression of α-smooth muscle actin (α-SMA) was elevated in UUO mice and all treatments except sEHi significantly attenuated renal α-SMA expression. Renal mRNA expression fibrotic and fibrosis regulators were higher in UUO mice and RB394 and sEHi + Rosi treatments attenuated their expression. Renal inflammation was evident in UUO mice with increased infiltration of CD45 and F4/80 positive cells. RB394 and sEHi + Rosi treatments attenuated renal inflammation in UUO mice. UUO mice had renal tubular and vascular injury. Renal tubular and vascular injuries were attenuated to a greater extent by RB394 and sEHi + Rosi than sEHi or Rosi treatment alone. Renal mRNA expression of oxidative stress markers were significantly higher in UUO mice (P < 0.05). RB394 and sEHi + Rosi attenuated expression of oxidative stress markers to a greater extent than other interventional treatments (P < 0.05). These findings demonstrate that RB394 can attenuate renal fibrosis by reducing renal inflammation, oxidative stress, tubular injury, and vascular injury. In conclusion, RB394 demonstrates exciting potential as a therapeutic for renal fibrosis and chronic kidney disease.

Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the pathogenesis of renal dysfunction in cirrhosis.

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver cirrhosis that is characterized by hemodynamic alterations in the kidney and other vascular beds. Cytochrome P(CYP)-450 enzymes metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acids. These eicosanoids regulate blood pressure, vascular tone and renal tubular sodium transport under both physiological and pathophysiological states. Methods: Experiments were performed to investigate the role of the CYP system in the pathogenesis of renal dysfunction during cirrhosis. Rats underwent bile duct ligation (BDL) or sham surgery and were studied at 2, 4 and 5 weeks post-surgery. In additional experiments, post-BDL rats were treated with three daily intraperitoneal doses of either the selective epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH) or a vehicle, starting on Day 22 after surgery. Results: BDL led to progressive renal dysfunction that was associated with reduced renal cortical perfusion but without any overt histologic changes, consistent with HRS. CYP isoform enzyme expression was significantly altered in BDL rats. In the kidney, CYP2C23 expression was upregulated at both the mRNA and protein levels in BDL rats, while CYP2C11 was downregulated. Histologically, the changes in CYP2C23 and CYP2C11 expression were localized to the renal tubules. EET production was increased in the kidneys of BDL rats as assessed by urinary eicosanoid levels. Finally, treatment with the selective epoxygenase inhibitor MSPPOH significantly reduced renal function and renal cortical perfusion in BDL rats, suggesting a homeostatic role for epoxygenase-derived eicosanoids. Conclusions: The CYP/EET pathway might represent a novel therapeutic target for modulating renal dysfunction in advanced cirrhosis.

The epoxyeicosatrienoic acid analog PVPA ameliorates cyclosporine-induced hypertension and renal injury in rats.

The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patients at risk of allograft rejection. Cytochrome P-450 epoxygenase metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), have potent vasodilator and antihypertensive properties in addition to many cytoprotective effects, but their effects on CNI-induced nephrotoxicity have not been explored. Here, we show that PVPA, a novel, orally active analog of 14,15-EET, effectively prevents the development of hypertension and ameliorates kidney injury in cyclosporine-treated rats. PVPA treatment reduced proteinuria and renal dysfunction induced by cyclosporine. PVPA inhibited inflammatory cell infiltration into the kidney and decreased renal fibrosis. PVPA also reduced tubular epithelial cell apoptosis, attenuated the generation of reactive oxygen species, and modulated the unfolded protein response that is associated with endoplasmic reticulum stress. Consistent with the in vivo data, PVPA attenuated cyclosporine-induced apoptosis of NRK-52E cells in vitro. These data indicate that the cytochrome P-450/EET system offers a novel therapeutic strategy to treat or prevent CNI-induced nephrotoxicity.

Perforated peptic ulcer.

Perforated peptic ulcer is a common emergency condition worldwide, with associated mortality rates of up to 30%. A scarcity of high-quality studies about the condition limits the knowledge base for clinical decision making, but a few published randomised trials are available. Although Helicobacter pylori and use of non-steroidal anti-inflammatory drugs are common causes, demographic differences in age, sex, perforation location, and underlying causes exist between countries, and mortality rates also vary. Clinical prediction rules are used, but accuracy varies with study population. Early surgery, either by laparoscopic or open repair, and proper sepsis management are essential for good outcome. Selected patients can be managed non-operatively or with novel endoscopic approaches, but validation of such methods in trials is needed. Quality of care, sepsis care bundles, and postoperative monitoring need further assessment. Adequate trials with low risk of bias are urgently needed to provide better evidence. We summarise the evidence for perforated peptic ulcer management and identify directions for future clinical research.

Prevalence of Inguinal Hernia in Adult Men in the Ashanti Region of Ghana.

BACKGROUND: Inguinal hernia is thought to be common in rural Ghana, though no recent data exist on hernia prevalence in the country. This information is needed to guide policy and increase access to safe hernia repair in Ghana and other low-resource settings. METHODS: Adult men randomly selected from the Barekese sub-district of Ashanti Region, Ghana were examined by surgeons for the presence of inguinal hernia. Men with hernia completed a survey on demographics, knowledge of the disease, and barriers to surgical treatment. RESULTS: A total of 803 participants were examined, while 105 participants completed the survey. The prevalence of inguinal hernia was 10.8 % (95 % CI 8.0, 13.6 %), and 2.2 % (95 % CI 0, 5.4 %) of participants had scars indicative of previous repair, making the overall prevalence of treated and untreated inguinal hernia 13.0 % (95 % CI 10.2, 15.7 %). Prevalence of inguinal hernia increased with age; 35.4 % (95 % CI 23.6, 47.2 %) of men aged 65 and older had inguinal hernia. Untreated inguinal hernia was associated with lower socio-economic status. Of those with inguinal hernia, 52.4 % did not know the cause of hernia. The most common reason cited for failing to seek medical care was cost (48.2 %). CONCLUSION: Although inguinal hernia is common among adult men living in rural Ghana, surgical repair rates are low. We propose a multi-faceted public health campaign aimed at increasing access to safe hernia repair in Ghana. This approach includes a training program of non-surgeons in inguinal hernia repair headed by the Ghana Hernia Society and could be adapted for use in other low-resource settings.

Magnesium protects against cisplatin-induced acute kidney injury without compromising cisplatin-mediated killing of an ovarian tumor xenograft in mice.

Cisplatin, a commonly used chemotherapeutic for ovarian and other cancers, leads to hypomagnesemia in most patients and causes acute kidney injury (AKI) in 25-30% of patients. Previously, we showed that magnesium deficiency worsens cisplatin-induced AKI and magnesium replacement during cisplatin treatment protects against cisplatin-mediated AKI in non-tumor-bearing mice (Solanki MH, Chatterjee PK, Gupta M, Xue X, Plagov A, Metz MH, Mintz R, Singhal PC, Metz CN. Am J Physiol Renal Physiol 307: F369-F384, 2014). This study investigates the role of magnesium in cisplatin-induced AKI using a human ovarian tumor (A2780) xenograft model in mice and the effect of magnesium status on tumor growth and the chemotherapeutic efficacy of cisplatin in vivo. Tumor progression was unaffected by magnesium status in saline-treated mice. Cisplatin treatment reduced tumor growth in all mice, irrespective of magnesium status. In fact, cisplatin-treated magnesium-supplemented mice had reduced tumor growth after 3 wk compared with cisplatin-treated controls. While magnesium status did not interfere with tumor killing by cisplatin, it significantly affected renal function following cisplatin. Cisplatin-induced AKI was enhanced by magnesium deficiency, as evidenced by increased blood urea nitrogen, creatinine, and other markers of renal damage. This was accompanied by reduced renal mRNA expression of the cisplatin efflux transporter Abcc6. These effects were significantly reversed by magnesium replacement. On the contrary, magnesium status did not affect the mRNA expression of cisplatin uptake or efflux transporters by the tumors in vivo. Finally, magnesium deficiency enhanced platinum accumulation in the kidneys and renal epithelial cells, but not in the A2780 tumor cells. These findings demonstrate the renoprotective role of magnesium during cisplatin AKI, without compromising the chemotherapeutic efficacy of cisplatin in an ovarian tumor-bearing mouse model.

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.

BACKGROUND: The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa. METHODS: Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression. RESULTS: The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p < 0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019). CONCLUSION: We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

"If You Need a Psychiatrist, It's BAD": Stigma Associated with Seeking Mental Health Care Among Obstetric Providers in Ghana.

Purpose: Globally, the COVID-19 pandemic has brought attention to the impact of negative patient outcomes on healthcare providers. In Ghana, obstetric providers regularly face maternal and neonatal mortality, yet limited research has focused on provision of mental health support for these providers. This study sought to understand how obstetric providers viewed seeking mental health support after poor clinical outcomes, with a focus on the role of mental health stigma. Patients and Methods: Participants were 52 obstetric providers (20 obstetrician/gynecologists and 32 midwives) at two tertiary care hospitals in Ghana. Five focus groups, led by a trained facilitator and lasting approximately two hours, were conducted to explore provider experiences and perceptions of support following poor maternal and neonatal outcomes. Discussions were audiotaped and transcribed verbatim, then analyzed qualitatively using grounded theory methodology. Results: Most participants (84.3%, N=43) were finished with training, and 46.2% (N=24) had been in practice more than 10 years. Emerging themes included pervasive stigma associated with seeking mental health care after experiencing poor clinical outcomes, which was derived from two overlapping dimensions. First, societal-level stigma resulted from a cultural norm to keep emotions hidden, and the perception that psychiatry is equated with severe mental illness. Second, provider-level stigma resulted from the belief that healthcare workers should not have mental health problems, a perception that mental health care is acceptable for patients but not for providers, and a fear about lack of confidentiality. Despite many providers acknowledging negative mental health impacts following poor clinical outcomes, these additive layers of stigma limited their willingness to engage in formal mental health care. Conclusion: This study demonstrates that stigma creates significant barriers to acceptance of mental health support among obstetric providers. Interventions to support providers will need to respect provider concerns without reinforcing the stigma associated with seeking mental health care.

Characterizing the global burden of surgical disease: a method to estimate inguinal hernia epidemiology in Ghana.

BACKGROUND: Surgical conditions represent an immense yet underrecognized source of disease burden globally. Characterizing the burden of surgical disease has been defined as a priority research agenda in global surgery. Little is known about the epidemiology of inguinal hernia, a common easily treatable surgical condition, in resource-poor settings. METHODS: Using data from the National Health and Nutrition Examination Survey prospective cohort study of inguinal hernia, we created a method to estimate hernia epidemiology in Ghana. We calculated inguinal hernia incidence and prevalence using Ghanaian demographic data and projected hernia prevalence under three surgical rate and hernia incidence scenarios. Disability adjusted life-years (DALYs) associated with inguinal hernia along with costs for surgical repair were estimated. RESULTS: According to this approach, the prevalence of inguinal hernia in the Ghanaian general population is 3.15% (range 2.79-3.50%). Symptomatic hernias number 530,082 (range 469,501-588,980). The annual incidence of symptomatic hernias is 210 (range 186-233) per 100,000 population. At the estimated Ghanaian hernia repair rate of 30 per 100,000, a backlog of 1 million hernias in need of repair develop over 10 years. The cost of repairing all symptomatic hernias in Ghana is estimated at US $53 million, and US $106 million would be required to eliminate hernias over a 10-year period. Nearly 5 million DALYs would be averted with the repair of prevalent cases of symptomatic hernia in Ghana. CONCLUSIONS: Data generated by our method indicate the extent to which Ghana lacks the surgical capacity to address its significant inguinal hernia disease burden. This approach provides a simple framework for calculating inguinal hernia epidemiology in resource-poor settings that may be used for advocacy and program planning in multiple country contexts.

Salt-sensitive hypertension after reversal of unilateral ureteral obstruction.

The incidence of ureter obstruction is increasing and patients recovering from this kidney injury often progress to chronic kidney injury. There is evidence that a long-term consequence of recovery from ureter obstruction is an increased risk for salt-sensitive hypertension. A reversal unilateral ureteral obstruction (RUUO) model was used to study long-term kidney injury and salt-sensitive hypertension. In this model, we removed the ureteral obstruction at day 10 in mice. Mice were divided into four groups: (1) normal salt diet, (2) high salt diet, (3) RUUO normal salt diet, and (4) RUUO high salt diet. At day 10, the mice were fed a normal or high salt diet for 4 weeks. Blood pressure was measured, and urine and kidney tissue collected. There was a progressive increase in blood pressure in the RUUO high salt diet group. RUUO high salt group had decreased sodium excretion and glomerular injury. Renal epithelial cell injury was evident in RUUO normal and high salt mice as assessed by neutrophil gelatinase-associated lipocalin (NGAL). Kidney inflammation in the RUUO high salt group involved an increase in F4/80 positive macrophages; however, CD3+ positive T cells were not changed. Importantly, RUUO normal and high salt mice had decreased vascular density. RUUO was also associated with renal fibrosis that was further elevated in RUUO mice fed a high salt diet. Overall, these findings demonstrate long-term renal tubular injury, inflammation, decreased vascular density, and renal fibrosis following reversal of unilateral ureter obstruction that could contribute to impaired sodium excretion and salt-sensitive hypertension.

Evidence of reduced academic performance among schoolchildren with helminth infection.

BACKGROUND: Soil-transmitted helminths (STHs) pose a formidable health risk to school-age children in resource-limited settings. Unfortunately, mass deworming campaigns have been derailed since the onset of the coronavirus disease 2019 pandemic. The present study assessed the cross-sectional associations between STHs, nutritional status and academic performance of schoolchildren in the Banda District of Ghana. METHODS: Schoolchildren (5-16 y of age; n=275) were recruited through both school and household visits by community health workers using a multistage cluster sampling technique. In addition to school microscopy, anthropometric records were also taken. RESULTS: The prevalence of geohelminthiasis was 40.4% (95% confidence interval 34.6 to 46.2). STHs targeted for elimination by the World Health Organization and national programmes were detected among schoolchildren. Children with intestinal parasite infection (53.7 [standard deviation {SD} 11.5]) had lower mean academic scores compared with uninfected children (59.6 [SD 16.9]) (p=0.034). In multiple regression analysis, intestinal parasite infection status and z-scores for weight-for-age showed a collective significant effect on the academic score (F1117=8.169, p<0.001, R2=0.125). CONCLUSIONS: Schoolchildren with STHs had poorer academic performance compared with uninfected children, despite their nutritional status. In addition to school feeding programmes, school-based mass drug administration campaigns may be critical for improving learning outcomes in young schoolchildren.

Update of the international HerniaSurge guidelines for groin hernia management.

BACKGROUND: Groin hernia repair is one of the most common operations performed globally, with more than 20 million procedures per year. The last guidelines on groin hernia management were published in 2018 by the HerniaSurge Group. The aim of this project was to assess new evidence and update the guidelines. The guideline is intended for general and abdominal wall surgeons treating adult patients with groin hernias. METHOD: A working group of 30 international groin hernia experts and all involved stakeholders was formed and examined all new literature on groin hernia management, available until April 2022. Articles were screened for eligibility and assessed according to GRADE methodologies. New evidence was included, and chapters were rewritten. Statements and recommendations were updated or newly formulated as necessary. RESULTS: Ten chapters of the original HerniaSurge inguinal hernia guidelines were updated. In total, 39 new statements and 32 recommendations were formulated (16 strong recommendations). A modified Delphi method was used to reach consensus on all statements and recommendations among the groin hernia experts and at the European Hernia Society meeting in Manchester on October 21, 2022. CONCLUSION: The HerniaSurge Collaboration has updated the international guidelines for groin hernia management. The updated guidelines provide an overview of the best available evidence on groin hernia management and include evidence-based statements and recommendations for daily practice. Future guideline development will change according to emerging guideline methodology.

Economic evaluation of expanding inguinal hernia repair among adult males in Ghana.

An unmet need for inguinal hernia repair is significant in Ghana where the number of specialist general surgeons is extremely limited. While surgical task sharing with medical doctors without formal specialist training in surgery has been adopted for inguinal hernia repair in Ghana, no prior research has been conducted on the long-term costs and health outcomes associated with expanding operations to repair all inguinal hernias among adult males in Ghana. The study aimed to estimate cost-effectiveness of elective open mesh repair performed by medical doctors and surgeons for adult males with primary inguinal hernia compared to no treatment in Ghana and to project costs and health gains associated with expanding operation services through task sharing between medical doctors and surgeons. The study analysis adopted a healthcare system perspective. A Markov model was constructed to assess 10-year differences in costs and outcomes between operations conducted by medical doctors or surgeons and no treatment. A 10-year budget impact analysis on service expansion for groin hernia repair through increasing task sharing between the providers was conducted. Incremental cost-effectiveness ratios for medical doctors and surgeons were USD 120 and USD 129 respectively per disability-adjusted life year (DALY) averted compared to no treatment, which are below the estimated threshold value for cost-effectiveness in Ghana of USD 371-491. Repairing all inguinal hernias (1.4 million) through task sharing between the providers in the same timeframe is estimated to cost USD 194 million. Total health gains of 1.5 million DALYs averted are expected. Inguinal hernia repair is cost-effective regardless of the type of surgical provider. Scaling up of inguinal hernia repair is worthwhile, with the potential to substantially reduce the disease burden in the country.

Cost-Effectiveness Analysis of Inguinal Hernia Repair With Mesh Performed by Surgeons and Medical Doctors in Ghana.

OBJECTIVES: Task-sharing is the pragmatic sharing of tasks between providers with different levels of training. To our knowledge, no study has examined the cost-effectiveness of surgical task-sharing of hernia repair in a low-resource setting. This study has aimed to evaluate and compare the cost-effectiveness of mesh repair performed by Ghanaian surgeons and medical doctors (MDs) following a standardized training program. METHODS: This cost-effectiveness analysis included data for 223 operations on adult men with primary reducible inguinal hernia. Cost per surgery was calculated from the healthcare system perspective. Disability weights were calculated using pre- and postoperative pain scores and benchmarks from the Global Burden of Disease Study 2017. RESULTS: The mean cost/disability-adjusted life-year (DALY) averted in the surgeon group was 444.9 United States dollars (USD) (95% confidence interval [CI] 221.2-668.5) and 278.9 USD (95% CI 199.3-358.5) in the MD group (P = .168), indicating that the operation is very cost-effective when performed by both providers. The incremental cost/DALY averted showed that task-sharing with MDs is also very cost-effective (95% bootstrap CI -436.7 to 454.9). The analysis found that increasing provider salaries is cost-effective if productivity remains high. When only symptomatic cases were analyzed, the mean cost/DALY averted reduced to 232.0 USD (95% CI 17.1-446.8) for the surgeon group and 129.7 USD (95% CI 79.6-179.8) for the MD group (P = .348), and the incremental cost/DALY averted increased by 45% but remained robust. CONCLUSIONS: Elective inguinal hernia repair with mesh performed by Ghanaian surgeons and MDs is a low-cost procedure and very cost-effective in the context of the study. To maximize cost-effectiveness, symptomatic patients should be prioritized over asymptomatic patients and a high level of productivity should be maintained.

Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b.

The cholinergic anti-inflammatory pathway is a physiological mechanism that inhibits cytokine production and diminishes tissue injury during inflammation. Recent studies demonstrate that cholinergic signaling reduces adhesion molecule expression and chemokine production by endothelial cells and suppresses leukocyte migration during inflammation. It is unclear how vagus nerve stimulation regulates leukocyte trafficking because the vagus nerve does not innervate endothelial cells. Using mouse models of leukocyte trafficking, we show that the spleen, which is a major point of control for cholinergic modulation of cytokine production, is essential for vagus nerve-mediated regulation of neutrophil activation and migration. Administration of nicotine, a pharmacologic agonist of the cholinergic anti-inflammatory pathway, significantly reduces levels of CD11b, a beta(2)-integrin involved in cell adhesion and leukocyte chemotaxis, on the surface of neutrophils in a dose-dependent manner and this function requires the spleen. Similarly, vagus nerve stimulation significantly attenuates neutrophil surface CD11b levels only in the presence of an intact and innervated spleen. Further mechanistic studies reveal that nicotine suppresses F-actin polymerization, the rate-limiting step for CD11b surface expression. These studies demonstrate that modulation of leukocyte trafficking via cholinergic signaling to the spleen is a specific, centralized neural pathway positioned to suppress the excessive accumulation of neutrophils at inflammatory sites. Activating this mechanism may have important therapeutic potential for preventing tissue injury during inflammation.