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Nicola Wearne,1 Kajiru Kilonzo,2 Emmanuel Effa,3 Bianca Davidson,1 Peter Nourse,4 Udeme Ekrikpo,1,5 Ikechi G Okpechi1 1Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa; 2Department of Medicine, Kilimanjaro Christian Medical College, Moshi, Tanzania; 3Department of Medicine, University of Calabar, Calabar, Nigeria; 4Division of Paediatric Nephrology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa; 5Department of Internal Medicine, University of Uyo, Uyo, Nigeria Abstract: Chronic kidney disease is a major public health problem that continues to show an unrelenting global increase in prevalence. The prevalence of chronic kidney disease has been predicted to grow the fastest in low- to middle-income countries (LMICs). There is evidence that people living in LMICs have the highest need for renal replacement therapy (RRT) despite the lowest access to various modalities of treatment. As continuous ambulatory peritoneal dialysis (CAPD) does not require advanced technologies, much infrastructure, or need for dialysis staff support, it should be an ideal form of RRT in LMICs, particularly for those living in remote areas. However, CAPD is scarcely available in many LMICs, and even where available, there are several hurdles to be confronted regarding patient selection for this modality. High cost of CAPD due to unavailability of fluids, low patient education and motivation, low remuneration for nephrologists, lack of expertise/experience for catheter insertion and management of complications, presence of associated comorbid diseases, and various socio-demographic factors contribute significantly toward reduced patient selection for CAPD. Cost of CAPD fluids seems to be a major constraint given that many countries do not have the capacity to manufacture fluids but instead rely heavily on fluids imported from developed countries. There is need to invest in fluid manufacturing (either nationally or regionally) in LMICs to improve uptake of patients treated with CAPD. Workforce training and retraining will be necessary to ensure that there is coordination of CAPD programs and increase the use of protocols designed to improve CAPD outcomes such as insertion of catheters, treatment of peritonitis, and treatment of complications associated with CAPD. Training of nephrology workforce in CAPD will increase workforce experience and make CAPD a more acceptable RRT modality with improved outcomes. Keywords: dialysis cost, dialysis fluid, peritoneal dialysis, peritonitis, nephrology workforce

Objectives: To identify, measure and value the economic burden of musculoskeletal (MSK) disorders in the Kilimanjaro region, Tanzania., Design: Community-based cross-sectional survey (undertaken between January and September 2021)., Setting: Hai district, Kilimanjaro, Tanzania., Participants: Households resident in the Hai district., Methods: A two-stage cluster sampling was used to select a representative sample of all Hai district residents. Clinical screening tools were used to identify and measure MSK disorders through a tiered approach. An economic questionnaire measuring healthcare costs, out-of-pocket costs, absenteeism, presenteeism and work productivity loss was administered to those with likely MSK disorders and selected controls (individuals without MSK disorders, matched by age and gender). Resource use was valued using country-specific costs. Two-part model regressions were fitted. A descriptive analysis of catastrophic expenditure was also conducted., Main Outcome Measure: Healthcare costs, productivity costs and total costs., Results: Annual average productivity and healthcare costs were, respectively, 3.5 and 3 times higher for those with likely MSK disorders than controls. Productivity costs of individuals with MSK disorders were Int$487 vs Int$132 in the control group (difference: Int$355, 95% CI Int$222 to Int$488). Healthcare costs in those with MSK were Int$269 vs Int$88 in the control group (difference: Int$181, 95% CI Int$34 to Int$327). The difference in terms of out-of-pocket expenses was economically substantial in magnitude, although not statistically significant., Conclusion: The evidence will be used to inform policies addressing MSK disorders, by promoting the design of interventions, service provision, health promotion and awareness activities at local, regional and national level., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Introduction: Over the past two decades, Tanzania's burden of non-communicable diseases has grown disproportionately, but limited resources are still prioritized. A trained human resource for health is urgently needed to combat these diseases. However, continuous medical education for NCDs is scarce. This paper reports on the mid-level healthcare workers knowledge on NCDs. We assessed the knowledge to measure the effectiveness of the training conducted during the initiation of a Package for Essential Management of Severe NCDs (PEN Plus) in rural district hospitals in Tanzania., Methods: The training was given to 48 healthcare employees from Dodoma Region's Kondoa Town Council District Hospital. For a total of five (5) days, a fundamental course on NCDs featured in-depth interactive lectures and practical workshops. Physicians from Tanzania's higher education institutions, tertiary university hospitals, research institutes, and medical organizations served as trainers. Before and after the training, a knowledge assessment comprising 28 questions was administered. Descriptive data analysis to describe the characteristics of the specific knowledge on physiology, diagnosis and therapy of diabetes mellitus, rheumatic fever, heart disease, and sickle cell disease was done using Stata version 17 (STATA Corp Inc., TX, USA)., Results: Complete assessment data for 42 out of the 48 participants was available. Six participants did not complete the training and the assessment. The mean age of participants was 36.9 years, and slightly above half (52%) were above 35 years. Two-thirds (61.9%) were female, and about half (45%) were nurses. The majority had the experience of working for more than 5 years, and the average was 9.4 years (+/- 8.4 years). Overall, the trainees' average scores improved after the training (12.79 vs. 16.05, p < 0.0001) out of 28 possible scores. Specifically, trainees' average scores were better in treatment than in diagnosis, except for sickle cell disease (1.26 vs. 1.83). Most were not able to diagnose rheumatic heart disease (47.6% able) compared to diabetes mellitus (54.8% able) or sickle cell disease (64.3% able) at baseline. The proportion of trainees with adequate knowledge of the treatment of sickle cell disease and diabetes mellitus was 35% and 38.1%, respectively, and there was a non-statistical difference after training. Those working for less than 5 years had a higher proportion of adequate knowledge (30.8%) compared to their more experienced colleagues (6.9%). After the training, participants' knowledge of NCDs increased by three times (i.e., aPR 3, 95% CI = 1.1, 1.5, and 6.0)., Conclusion and Recommendations: PEN Plus training improved the knowledge of healthcare workers at Kondoa Town Council District Hospital. Training is especially needed among nurses and those with a longer duration of work. Continuing education for human resources for health on the management of NCDs is highly recommended in this setting., (© 2024. The Author(s).)

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I 2  = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease., (© 2023. The Author(s).)

Objective: The burden of stroke has increased in recent years worldwide, particularly in low-income and middle-income countries. In this study we aim to determine the number of stroke admissions, and associated comorbidities, at a referral hospital in Northern Tanzania., Design: This was a retrospective observational study., Setting: The study was conducted at a tertiary referral hospital, Kilimanjaro Christian Medical Centre (KCMC), in the orthern zone of Tanzania., Participants: The study included adults aged 18 years and above, who were admitted to the medical wards from 2017 to 2019., Outcome: The primary outcome was the proportion of patients who had a stroke admitted in the medical ward at KCMC and the secondary outcome was clinical outcome such as mortality., Methods: We conducted a retrospective audit of medical records from 2017 to 2019 for adult patients admitted to the medical ward at KCMC. Data extracted included demographic characteristics, previous history of stroke and outcome of the admission. Factors associated with stroke were investigated using logistic regression., Results: Among 7976 patients admitted between 2017 and 2019, 972 (12.2%) were patients who had a stroke. Trends show an increase in patients admitted with stroke over the 3 years with 222, 292 and 458 in 2017, 2018 and 2019, respectively. Of the patients who had a stroke, 568 (58.4%) had hypertension while 167 (17.2%) had diabetes mellitus. The proportion of admitted stroke patients aged 18-45 years, increased from 2017 (n=28, 3.4%) to 2019 (n=40, 4.3%). The in-hospital mortality related to stroke was 229 (23.6%) among 972 patients who had a stroke and female patients had 50% higher odds of death as compared with male patients (OR:1.5; CI 1.30 to 1.80)., Conclusion: The burden of stroke on individuals and health services is increasing over time, which reflects a lack of awareness on the cause of stroke and effective preventive measures. Prioritising interventions directed towards the reduction of non-communicable diseases and associated complications, such as stroke, is urgently needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Castleman's disease is a rare lympho-proliferative disease entity characterized by variable clinical presentations, distinctive histological manifestations, and prognosis. Its incidence and etiology are unclear. An interplay of HIV and human herpesvirus-8 has been implicated. Although its localized variety is benign, other types can be multifocal with adverse systemic manifestations. Human herpesvirus-8 Castleman's disease affects mainly HIV-positive individuals; however, individuals who are immunocompromised from other causes can also be affected, thus necessitating investigations for HIV. Herein, we report two patients presenting with long-standing lymphadenopathy. Histopathology, immunohistochemical testing and clinico-pathological correlation confirmed the diagnosis of Castleman's disease. The patients were successfully treated with surgery and/or rituximab. They were symptoms free in the subsequent follow-up visits. A brief review of the literature is also provided., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes., Methods: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications., Results: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I 2 =94.7%), 38% (95% CI 30 to 46, I 2 =98.7%) and 42% (95% CI 32 to 52, I 2 =97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I 2 =98.2%), 32% (95% CI 28 to 36, I 2 =98%), 31% (95% CI 22 to 41, I 2 =99.3%), 19% (95% CI 12 to 25, I 2 =98.1%) and 11% (95% CI 9 to 14, I 2 =97.4%), respectively., Conclusion: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Each year several Mt. Kilimanjaro hikers die due to altitude illness (AI) although urgent descent is technically easily possible. The objectives of this study were to determine the incidence and predictors of severe altitude illness (SAI) symptoms and of summit success in Mt. Kilimanjaro hikers, and the measures taken when AI symptoms develop., Methods: A prospective observational cohort study in Mt. Kilimanjaro hikers was conducted from December 2019 until March 2020. Participants were asked to complete a questionnaire at the entrance gate and one at the descend gate. A multivariate logistic regression was performed to study the relations between the variables., Results: A total of 1237 recreational hikers and 266 porters or guides were included. The incidence of severe symptoms was 8.6% in recreational hikers and 1.5% in porters and guides. One percent (1.1%) of hikers was hospitalized due to SAI. A history of SAI, young age, summit failure and lack of clear advice predicted the development of severe symptoms. Uhuru peak was reached by 87.9% of the hikers. Absence of severe symptoms, acetazolamide prophylaxis, climbing higher in daytime, young age and climbing in more days predicted summit success. The majority climbed further despite the presence of mild or severe symptoms. The only measure taken in case of mild symptoms that was associated with a lower incidence of severe symptoms was not climbing further., Conclusion: The incidence of SAI symptoms in Mt. Kilimanjaro hikers was observed to be high. However, how hikers reacted during symptoms was not appropriate. Therefore, travel health counsellors should emphasize even more that hikers do not ascend higher until mild symptoms have resolved and that it is vital to descend immediately when severe symptoms develop. In addition, they can be informed on the measures, which improved summit success., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Ethnic groups differ in prevalence of calcium-related diseases. Differences in the physiology and the endogenous circadian rhythm (CR) of calcium and bone homeostasis may play a role. Thus, we aimed to investigate details of CR pattern in calcium and bone homeostasis in East African Maasai., Methods: Ten clinically healthy adult Maasai men and women from Tanzania were examined. Blood samples were collected every 2nd hour for 24 h. Serum levels of total calcium, albumin, parathyroid hormone (PTH), 25(OH)D, creatinine, C-terminal telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin were measured. Circadian patterns were derived from graphic curves of medians, and rhythmicity was assessed with Fourier analysis., Results: PTH-levels varied over the 24 h exhibiting a bimodal pattern. Nadir level corresponded to 65% of total 24-h mean. CTX and P1NP showed 24-h variations with a morning nadir and nocturnal peak with nadir levels corresponding to 23% and 79% of the 24-h mean, respectively. Albumin-corrected calcium level was held in a narrow range and alterations were corresponding to alterations in PTH. There was no distinct pattern in 24-h variations of 25(OH)D, creatinine, osteocalcin, or BSAP., Conclusions: All participants showed pronounced 24-h variations in PTH and bone turnover markers CTX and P1NP. These findings support that Maasai participants included in this study have typical patterns of CR in calcium and bone homeostasis consistent with findings from other ethnic populations., (© 2022 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy. In this case report, we will discuss a 31-year-old male who presented with a chief complaint of low-grade fevers, dry cough and difficulty breathing for about two weeks which preceded after removing of dental also two weeks prior. He was admitted and treated as COVID-19 in the isolation ward, he later developed cardiac tamponade and during pericardiocentesis thick pus was discharged. Pus culture and Gene Xpert tests were all negative. After his condition improved, the patient was transferred to the general ward with the pericardial window still discharging pus. Pericardiectomy was chosen as definitive management. The key takeaway in this report is that Empirical treatment with RHZE (rifampin, isoniazid, pyrazinamide, and ethambutol) in resource-limited settings is recommended due to difficulty in identifying the exact cause at a required moment., Competing Interests: The authors declare no competing interests., (Copyright: Proches Vara et al.)

Background: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP)., Methods: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM., Discussion: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control., Trial Registration: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020., (© 2022. The Author(s).)

Schizophrenia is associated with a broad range of severe and currently pharmacoresistant cognitive deficits. Prior evidence suggests that hypofunction of AMPA-type glutamate receptors (AMPARs) containing the subunit GLUA1, encoded by GRIA1, might be causally related to impairments of selective attention and memory in this disorder, at least in some patients. In order to clarify the roles of GluA1 in distinct cell populations, we investigated behavioural consequences of selective Gria1-knockout in excitatory neurons of subdivisions of the prefrontal cortex and the hippocampus, assessing sustained attention, impulsivity, cognitive flexibility, anxiety, sociability, hyperactivity, and various forms of short-term memory in mice. We found that virally induced reduction of GluA1 across multiple hippocampal subfields impaired spatial working memory. Transgene-mediated ablation of GluA1 from excitatory cells of CA2 impaired short-term memory for conspecifics and objects. Gria1 knockout in CA3 pyramidal cells caused mild impairments of object-related and spatial short-term memory, but appeared to partially increase social interaction and sustained attention and to reduce motor impulsivity. Our data suggest that reduced hippocampal GluA1 expression-as seen in some patients with schizophrenia-may be a central cause particularly for several short-term memory deficits. However, as impulse control and sustained attention actually appeared to improve with GluA1 ablation in CA3, strategies of enhancement of AMPAR signalling likely require a fine balance to be therapeutically effective across the broad symptom spectrum of schizophrenia., (© 2022. The Author(s).)

Pathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of G i -signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among G i -coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest G i -coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

In the African esophageal squamous cell carcinoma (ESCC) corridor, recent work from Kenya found increased ESCC risk associated with poor oral health, including an ill-understood association with dental fluorosis. We examined these associations in a Tanzanian study, which included examination of potential biases influencing the latter association. This age and sex frequency-matched case-control study included 310 ESCC cases and 313 hospital visitor/patient controls. Exposures included self-reported oral hygiene and nondental observer assessed decayed+missing+filled tooth count (DMFT index) and the Thylstrup-Fejerskov dental fluorosis index (TFI). Blind to this nondental observer TFI, a dentist independently assessed fluorosis on photographs of 75 participants. Odds ratios (ORs) are adjusted for demographic factors, alcohol and tobacco. ESCC risk was associated with using a chewed stick to brush teeth (OR 2.3 [95% CI: 1.3-4.1]), using charcoal to whiten teeth (OR 2.13 [95% CI: 1.3, 4.1]) and linearly with the DMFT index (OR 3.3 95% CI: [1.8, 6.0] for ≥10 vs 0). Nondental observer-assessed fluorosis was strongly associated with ESCC risk (OR 13.5 [95% CI: 5.7-31.9] for TFI 5+ v 0). However, the professional dentist's assessment indicated that only 43% (10/23) of participants assessed as TFI 5+ actually had fluorosis. In summary, using oral charcoal, brushing with a chewed stick and missing/decayed teeth may be risk factors for ESCC in Tanzania, for which dose-response and mechanistic research is needed. Links of ESCC with "dental fluorosis" suffered from severe exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining or reverse causality., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

A hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.

Summary Statements: (1) Peritoneal dialysis (PD) should be considered a suitable modality for treatment of acute kidney injury (AKI) in all settings (1B) ., Guideline 2: Access and Fluid Delivery for Acute Pd in Adults: (2.1) Flexible peritoneal catheters should be used where resources and expertise exist (1B) (optimal) .(2.2) Rigid catheters and improvised catheters using nasogastric tubes and other cavity drainage catheters may be used in resource-poor environments where they may still be life-saving (1C) (minimum standard) .(2.3) We recommend catheters should be tunnelled to reduce peritonitis and peri-catheter leak (practice point) .(2.4) We recommend that the method of catheter implantation should be based on patient factors and locally available skills (1C) .(2.5) PD catheter implantation by appropriately trained nephrologists in patients without contraindications is safe and functional results equate to those inserted surgically (1B) .(2.6) Nephrologists should receive training and be permitted to insert PD catheters to ensure timely dialysis in the emergency setting (practice point). (2.7) We recommend, when available, percutaneous catheter insertion by a nephrologist should include assessment with ultrasonography (2C) .(2.8) Insertion of PD catheter should take place under complete aseptic conditions using sterile technique (practice point) .(2.9) We recommend the use of prophylactic antibiotics prior to PD catheter implantation (1B) .(2.10) A closed delivery system with a Y connection should be used (1A) (optimal) . In resource poor areas, spiking of bags and makeshift connections may be necessary and can be considered (minimum standard) .(2.11) The use of automated or manual PD exchanges are acceptable and this will be dependent on local availability and practices (practice point) ., Guideline 3: Peritoneal Dialysis Solutions for Acute Pd: (3.1) In patients who are critically ill, especially those with significant liver dysfunction and marked elevation of lactate levels, bicarbonate containing solutions should be used ( 1B) (optimal) . Where these solutions are not available, the use of lactate containing solutions is an alternative (practice point) (minimum standard) .(3.2) Commercially prepared solutions should be used (optimal) . However, where resources do not permit this, then locally prepared fluids may be life-saving and with careful observation of sterile preparation procedure, peritonitis rates are not increased (1C) (minimum standard) .(3.3) Once potassium levels in the serum fall below 4 mmol/L, potassium should be added to dialysate (using strict sterile technique to prevent infection) or alternatively oral or intravenous potassium should be given to maintain potassium levels at 4 mmol/L or above (1C) .(3.4) Potassium levels should be measured daily (optimal) . Where these facilities do not exist, we recommend that after 24 h of successful dialysis, one consider adding potassium chloride to achieve a concentration of 4 mmol/L in the dialysate (minimum standard) (practice point)., Guideline 4: Prescribing and Achieving Adequate Clearance in Acute Pd: (4.1) Targeting a weekly K t / V urea of 3.5 provides outcomes comparable to that of daily HD in critically ill patients; targeting higher doses does not improve outcomes (1B) . This dose may not be necessary for most patients with AKI and targeting a weekly K t / V of 2.2 has been shown to be equivalent to higher doses (1B) . Tidal automated PD (APD) using 25 L with 70% tidal volume per 24 h shows equivalent survival to continuous venovenous haemodiafiltration with an effluent dose of 23 mL/kg/h (1C) .(4.2) Cycle times should be dictated by the clinical circumstances. Short cycle times (1-2 h) are likely to more rapidly correct uraemia, hyperkalaemia, fluid overload and/or metabolic acidosis; however, they may be increased to 4-6 hourly once the above are controlled to reduce costs and facilitate clearance of larger sized solutes (2C) .(4.3) The concentration of dextrose should be increased and cycle time reduced to 2 hourly when fluid overload is evident. Once the patient is euvolemic, the dextrose concentration and cycle time should be adjusted to ensure a neutral fluid balance (1C) .(4.4) Where resources permit, creatinine, urea, potassium and bicarbonate levels should be measured daily; 24 h K t / V urea and creatinine clearance measurement is recommended to assess adequacy when clinically indicated (practice point) .(4.5) Interruption of dialysis should be considered once the patient is passing >1 L of urine/24 h and there is a spontaneous reduction in creatinine (practice point) ., The use of peritoneal dialysis (PD) to treat patients with acute kidney injury (AKI) has become more popular among clinicians following evidence of similar outcomes when compared with other extracorporeal therapies. Although it has been extensively used in low-resource environments for many years, there is now a renewed interest in the use of PD to manage patients with AKI (including patients in intensive care units) in higher income countries. Here we present the update of the International Society for Peritoneal Dialysis guidelines for PD in AKI. These guidelines extensively review the available literature and present updated recommendations regarding peritoneal access, dialysis solutions and prescription of dialysis with revised targets of solute clearance.

Hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs), whether caused by endogenous factors like auto-antibodies or mutations, or by pharmacological or genetic manipulations, produces a wide variety of deficits which overlap with-but do not precisely match-the symptom spectrum of schizophrenia. In order to understand how NMDAR hypofunction leads to different components of the syndrome, it is necessary to take into account which neuronal subtypes are particularly affected by it in terms of detrimental functional alterations. We provide a comprehensive overview detailing findings in rodent models with cell type-specific knockout of NMDARs. Regarding inhibitory cortical cells, an emerging model suggests that NMDAR hypofunction in parvalbumin (PV) positive interneurons is a potential risk factor for this disease. PV interneurons display a selective vulnerability resulting from a combination of genetic, cellular, and environmental factors that produce pathological multi-level positive feedback loops. Central to this are two antioxidant mechanisms-NMDAR activity and perineuronal nets-which are themselves impaired by oxidative stress, amplifying disinhibition. However, NMDAR hypofunction in excitatory pyramidal cells also produces a range of schizophrenia-related deficits, in particular maladaptive learning and memory recall. Furthermore, NMDAR blockade in the thalamus disturbs thalamocortical communication, and NMDAR ablation in dopaminergic neurons may provoke over-generalization in associative learning, which could relate to the positive symptom domain. Therefore, NMDAR hypofunction can produce schizophrenia-related effects through an action on various different circuits and cell types., (Copyright © 2019 Bygrave, Kilonzo, Kullmann, Bannerman and Kätzel.)

Background: The burden of kidney diseases is reported to be higher in lower- and middle-income countries as compared to developed countries, and countries in sub-Saharan Africa are reported to be most affected. Health systems in most sub-Sahara African countries have limited capacity in the form of trained and skilled health care providers, diagnostic support, equipment and policies to provide nephrology services. Several initiatives have been implemented to support establishment of these services., Methods: This is a situation analysis to examine the nephrology services in Tanzania. It was conducted by interviewing key personnel in institutions providing nephrology services aiming at describing available services and international collaborators supporting nephrology services., Results: Tanzania is a low-income country in Sub-Saharan Africa with a population of more than 55 million that has seen remarkable improvement in the provision of nephrology services and these include increase in the number of nephrologists to 14 in 2018 from one in 2006, increase in number of dialysis units from one unit (0.03 unit per million) before 2007 to 28 units (0.5 units per million) in 2018 and improved diagnostic services with introduction of nephropathology services. Government of Tanzania has been providing kidney transplantation services by funding referral of donor and recipients abroad and has now introduced local transplantation services in two hospitals. There have been strong international collaborators who have supported nephrology services and establishment of nephrology training in Tanzania., Conclusion: Tanzania has seen remarkable achievement in provision of nephrology services and provides an interesting model to be used in supporting nephrology services in low income countries.

Background: According to World Health Organization (WHO) the final multidrug resistant tuberculosis (MDRTB) treatment outcome is the most important direct measurement of the effectiveness of the MDRTB control program. Literature review has shown marked diversity in predictors of treatment outcomes worldwide even among the same continents. Therefore, findings could also be different in Tanzanian context, where the success rate is still lower than the WHO recommendation. This study sought to determine the predictors of treatment outcomes among MDRTB patients in Tanzania in order to improve the success rate., Methodology: This was a retrospective cohort study, which was conducted at Kibong'oto Infectious Diseases Hospital (KIDH) in Tanzania. Patients' demographic and clinical parameters were collected from the MDRTB registry and clinical files. Then, a detailed analysis was done to determine the predictors of successful and unsuccessful MDRTB treatment outcomes., Results: Three hundred and thirty-two patients were diagnosed and put on MDRTB treatment during the year 2009 to 2014. Among them, males were 221 (67%), and 317 (95.48%) were above 18 years of age, mean age being 36.9 years. One hundred and sixty-one patients (48.5%) were living in Dar es Salaam. The number of MDRTB patients has increased from 16 in 2009 to 132 in 2014. Majority of patients (75.7%) had successful treatment outcomes. The following predictors were significantly associated with MDRTB cure: presence of cavities in chest X-rays (aOR 1.89, p value 0.002), low BMI (aOR 0.59, p value 0.044), and resistance to streptomycin (aOR 4.67, p value 0.007) and ethambutol (aOR 0.34, p value 0.041). Smoking and presence of cavities in chest X-rays were associated with MDRTB mortality, aOR 2.31, p value 0.043 and aOR 0.55, p value 0.019, respectively., Conclusion: The study indicated that overall number of MDRTB patients and the proportion of successful treatment outcomes have been increasing over the years. The study recommends improving nutritional status of MDRTB patients, widespread antismoking campaign, and close follow-up of patients with ethambutol resistance.

Objectives: To determine the sociodemographic characteristics, clinical findings and outcome by HIV status in a series of adult patients presenting with neurological disorders (NDs) and admitted to a consultant hospital in Northern Tanzania., Methods: A cohort study took place over a 6-month period from Oct 2007 to March 2008 and included all adult patients with a neurological disorder admitted to the medical wards., Results: A total of 1790 patients were admitted during this period, of whom 337 (18.8%) were diagnosed with a neurological disorder and formed the study group. Of these 337, 69 (20.5%) were HIV-positive. Among the 69 HIV positives, 25% were previously known to be HIV seropositive of whom 82% were on antiretroviral (ARV) medication. Seropositive patients were more likely than seronegative patients to be younger, better educated, have a business occupation, present clinically with confusion, headache and aphasia and have meningitis/CNS infection or a space occupying lesion. Seropositive patients were more likely to present with a Glasgow Coma Score (GCS) of 9-12/15 (33.3% v 17.2%). Seropositive patients had a median CD4 T-lymphocyte count of 47cells/L and were more likely to be anaemic and have an elevated ESR. CT of the head was carried out on 132/337 (39%) patients. The overall findings were infarction 37%, hemorrhage 19%, tumors 15% and abscesses 9%. Brain abscess was more likely in seropositive patients and hemorrhage in seronegatives. The outcome at discharge for all patients was: death 27.6%, disability 54% and no disability 18.4% with death (39.1%) being more likely in seropositive patients. Patients presenting with coma (GCS <9/15) were more likely to die whilst those with stroke, para/quadriplegia and space occupying lesions (SOLs) were more likely to be discharged with disability. Case fatality rate was highest for tetanus 71.4%, meningitis 57.1%, cerebral malaria 42.9% and CNS infections 37.1%. Seropositive patients presenting with meningitis and other CNS infections were more likely to die than seronegatives., Conclusion: This study reports NDs occurring in one fifth of adult medical admissions with stroke and infections as the leading causes. The prevalence of HIV infection in NDs was 20%. The HIV positive cohort was characterized by advanced immunosuppression, CNS infections and high mortality.

Bee sting has been identified as among causative agents of nephrotoxic acute tubular necrosis which may lead to acute kidney injury. Bee envenomation has medicinal properties but when a higher dose is inoculated may cause severe anaphylaxis with very poor prognosis. We report a 12-year-old boy with acute kidney injury following multiple bee stings who recovered well after hemodialysis.

Background: Locomotor activity of rodents is an important readout to assess well-being and physical health, and is pivotal for behavioral phenotyping. Measuring homecage-activity with standard and cost-effective optical methods in mice has become difficult, as modern housing conditions (e.g. individually ventilated cages, cage enrichment) do not allow constant, unobstructed, visual access. Resolving this issue either makes greater investments necessary, especially if several experiments will be run in parallel, or is at the animals' expense. The purpose of this study is to provide an easy, yet satisfying solution for the behavioral biologist at novice makers level., Results: We show the design, construction and validation of a simplified, low-cost, radar-based motion detector for home cage activity monitoring in mice. In addition we demonstrate that mice which have been selectively bred for low levels of anxiety-related behavior (LAB) have deficits in circadian photoentrainment compared to CD1 control animals., Conclusion: In this study we have demonstrated that our proposed low-cost microwave-based motion detector is well-suited for the study of circadian rhythms in mice.

Introduction: In sub-Saharan Africa, approximately 100 million people have CKD, yet genetic risk factors are not well-understood. Despite the potential importance of understanding APOL1 risk allele status among individuals with CKD, little genetic research has been conducted. Therefore, we conducted a pilot study evaluating the feasibility of and willingness to participate in genetic research on kidney disease, and we estimated APOL1 risk allele frequencies among individuals with CKD., Methods: In 2014, we conducted a community-based field study evaluating CKD epidemiology in northern Tanzania. We assessed for CKD using urine albumin and serum creatinine to estimate GFR. We invited participants with CKD to enroll in an additional genetic study. We obtained dried-blood spots on filter cards, from which we extracted DNA using sterile punch biopsies. We genotyped for two single nucleotide polymorphisms (SNPs) defining the APOL1 G1 risk allele and an insertion/deletion polymorphism defining the G2 risk allele. Genotyping was performed in duplicate., Results: We enrolled 481 participant, 57 (12%) of whom had CKD. Among these, enrollment for genotyping was high (n = 48; 84%). We extracted a median of 19.4 ng of DNA from each dried-blood spot sample, and we genotyped the two APOL1 G1 SNPs and the APOL1 G2 polymorphism. Genotyping quality was high, with all duplicated samples showing perfect concordance. The frequency of APOL1 risk variants ranged from 7.0% to 11.0%, which was similar to previously-reported frequencies from the general population of northern Tanzania (p>0.2)., Discussion: In individuals with CKD from northern Tanzania, we demonstrated feasibility of genotyping APOL1 risk alleles. We successfully genotyped three risk variants from DNA extracted from filter cards, and we demonstrated a high enrollment for participation. In this population, more extensive genetic studies of kidney disease may be well-received and will be feasible.

Traditional medicines are a principal form of health care for many populations, particularly in low- and middle-income countries, and they have gained attention as an important means of health care coverage globally. In the context of kidney diseases, the challenges and opportunities presented by traditional medicine practices are among the most important considerations for developing effective and sustainable public health strategies. However, little is known about the practices of traditional medicines in relation to kidney diseases, especially concerning benefits and harms. Kidney diseases may be caused, treated, prevented, improved, or worsened by traditional medicines depending on the setting, the person, and the types, modes, and frequencies of traditional medicine use. Given the profound knowledge gaps, nephrology practitioners and researchers may be uniquely positioned to facilitate more optimal public health strategies through recognition and careful investigation of traditional medicine practices. Effective implementation of such strategies also will require local partnerships, including engaging practitioners and users of traditional medicines. As such, practitioners and researchers investigating kidney diseases may be uniquely positioned to bridge the cultural, social, historical, and biologic differences between biomedicine and traditional medicine, and they have opportunities to lead efforts in developing public health strategies that are sensitive to these differences., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Avoiding associatively learned predictors of danger is crucial for survival. Aversive memories can, however, become counter-adaptive when they are overly generalized to harmless cues and contexts. In a fruit fly odor-electric shock associative memory paradigm, we found that learned avoidance lost its specificity for the trained odor and became general to novel odors within a day of training. We discuss the possible neural circuit mechanisms of this effect and highlight the parallelism to over-generalization of learned fear behavior after an incubation period in rodents and humans, with due relevance for post-traumatic stress disorder., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Obesity, mild intellectual disability, hypotonia, poor sucking, cryptorchidism in males, hypogonadism, and kyphoscoliosis are common features of Prader-Willi syndrome (PWS). We report a case who had severe respiratory complications due to extreme obesity and kyphoscoliosis, which are important causes of morbidity and mortality, and discuss management. Furthermore, this is the first molecularly confirmed PWS case in Sub-Saharan Africa outside South Africa.

Background: The risk factors for prevalent delirium in older hospitalised adults in Sub-Saharan Africa (SSA) remain poorly characterised., Methods: A total of 510 consecutive admissions of adults aged ≥60 years to acute medical wards of Kilimanjaro Christian Medical Centre in northern Tanzania were recruited. Patients were assessed within 24 h of admission with a risk factor questionnaire, physiological observations, neurocognitive assessment, and informant interview. Delirium and dementia diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM V) and DSM IV respectively, by an expert panel., Results: Being male, current alcohol use, dementia, and physiological markers of illness severity were significant independent risk factors for delirium on multivariable analysis., Conclusions: The risk factors for prevalent delirium in older medical inpatients in SSA include pre-existing dementia, and are similar to those identified in high-income countries. Our data could help inform the development of a delirium risk stratification tool for older adults in SSA., (© 2017 S. Karger AG, Basel.)

Background: Chorea is a rare complication of uncontrolled type II diabetes. We report for the first time in Tanzania a case of type II diabetes presenting with a hyperglycaemia-induced hemichorea., Case Presentation: A 58-year-old Tanzanian chagga by tribe with a body mass index of 28 kg/m(2) and newly diagnosed type II diabetes presented with polydipsia and involuntary movements of the right upper limb for 4 days. His plasma glucose was 549 mg/dl and glycated haemoglobin was 18.9 %. His movements were exaggerated by attempts to use his right hand. The rest of his neurological assessment was unremarkable. Other laboratory findings including calcium were within the normal range. A computed tomography scan of the brain was essentially normal except for age-related atrophy. There was no significant ketonuria on urine dipstick testing. We treated the patient's hyperglycaemia with intravenous insulin and the dystonia disappeared within 5 days., Conclusion: Hemichorea is among the rare complications of hyperglycaemia-induced involuntary movements. Hyperglycaemia should be considered as a differential diagnosis for patients with type II diabetes mellitus presenting with hemichorea upon clinical assessment.