AN ETHNOGRAPHIC STUDY ON THE PERCEIVED SPIRITUAL CAUSES OF PSYCHOSIS IN CENTRAL UGANDA.

Background The WHO defines health as the complete physical, mental, and social well-being and not simply the absence of disease. Unfortunately, many are increasingly suffering from mental illness especially following the recent COVID-19 pandemic characterized by psychosis among other symptoms. According to the DSM-5, psychosis is characterized by the following: “delusions, hallucinations, disorganized speech, catatonia or abnormal motor behaviour, and negative symptoms” which greatly disrupt human life and relationships. Although there are conventional ways of managing psychosis, people still seek spiritual modalities due to the perceived spiritual causes. This study, therefore, sought to identify and document the perceived spiritual causes of psychosis in Central Uganda from July to December 2022. Methodology An ethnographic study design was employed for this explorative qualitative study. The sample size was 15 which was obtained through saturation. Sampling was carried out using the snowball method and the respondents were traditional healers, Christians, and Muslims who practiced spiritual management of psychosis as well as their clients (patients and caregivers). In-depth Interviews and Key informant interviews as well as observations were used for data collection. Data were analysed thematically. Results The spiritual cause of Psychosis in the study area was found to be demons (evil spirits). These were either ancestral in nature or a result of witchcraft. Witchcraft was either sent or self-inflicted.  Conclusion There is a spiritual world that can influence and inflict disease in the physical body including mental illness (psychosis).    Recommendation Research needs to be done to establish whether the disease progress and manifestations are similar in one who has psychosis as a result of spiritual causes compared to one whose psychotic symptoms are a result of purely physical causes

CHILD HEALTH AND SAFETY OF COMPLEMENTARY FOOD AMONG HOUSEHOLDS IN ADYEL DIVISION, LIRA DISTRICT: A CROSS-SECTIONAL STUDY.

Background Safe complementary food is food that will not cause harm to infants and children when prepared and fed as recommended. Unfortunately, children are frequently suffering from diarrhoea which is not only preventable but is also largely attributed to complementary foods hence this study.   Methodology The study was carried out in 2015 in Adyel Division, Lira District among caregiver-child pairs. The children were between the ages of 6 – 23 months. Information collected was about the children’s diarrhoeal patterns, nutritional status, and complementary food safety. Results Analyses of food samples revealed that freshly cooked food was contaminated with fecal coliforms (4.88±1.87 log cfu/g), and the levels of fecal coliforms in stored food increased with prolonged storage period (5.49b±1.86 log cfu/g).  Drinking water too was contaminated with E.coli (2.86 logs cfu/ml). Water in storage containers had total coliform counts of up to 3.14 log cfu/ml. In over half of the households (56.7%), the microbial counts in household drinking water containers (4.48E+03cfu E.coli) were more than those found at the respective water sources (4.46E+02cfu E.coli). Water treatment accounted for 25% of the variation (p=0.005) in E.coli counts in drinking water that was found in water storage containers. About 32.5% of the frequency or recurrence of diarrhea episodes in two weeks among children was explained by the presence of fecal coliforms in freshly cooked complementary food (p=0.001). Overall, diarrheal infections (p=0.030), inappropriate child-feeding practices (p=0.048), and poor hand-washing (p=0.011) played a significant role in influencing child health.  Conclusion The food safety in this study was compromised by poor complementary food handling practices. Recommendation There is a need to study specific food combinations under more controlled conditions to compare the effect of the different handling practices on the microbial load in the various foods

Prevalence and Severity of Premenstrual Syndrome among Female University Students in Central Uganda: A Cross-sectional Study

Background Premenstrual Syndrome (PMS) is characterized by recurrent psychological, behavioural, and/or physical symptoms occurring before menses and usually resolve by the end of or during menstruation. These symptoms usually affect the women’s quality of life and efficiency. Although over 95% of women worldwide suffer from PMS, in Uganda, little is documented about the prevalence and existence of PMS among students. This study, therefore, sought to determine the prevalence and severity of PMS among female university students in Central Uganda. Methodology A cross-sectional study was carried out using a questionnaire between November 2021 and May 2022. The sample of 238 participants was taken from female students in 4 universities who met the inclusion criteria. Sampling was done by proportionate sampling. Primary data was obtained about Premenstrual Syndrome prevalence and severity using modifications of the following tools: The American College of Obstetricians and Gynecologists' diagnostic criteria for PMS; the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-IV) diagnostic criteria for PMDD; and the premenstrual symptoms screening tool (PSST). The data was analysed to obtain descriptive statistics such as frequencies and percentages. A student was considered to be suffering from PMS if they satisfied the DSM-IV criteria for the diagnosis of PMS.  Results The prevalence of PMS among female University students in central Uganda was found to be 28.3% (60). However, at least 76.9% (163) of the respondents suffered at least one or more symptoms of PMS.  Conclusion Over a quarter of female university students suffer from Premenstrual syndrome. Recommendation There is a need to create awareness as well as mobilize social support so that there is help available to the students who suffer PMS

Social-demographic factors associated with Premenstrual Syndrome among female University students in Central Uganda: A Cross-sectional Study.

Background Premenstrual Syndrome (PMS) is a common disorder among females of reproductive age, which also happens to be the most productive period within the life of a woman. Unfortunately, the aetiology of PMS is still not known; although, the following theories have been proposed to explain PMS symptoms: A genetic predisposition; changes in neurotransmitter levels; or changes in different hormone levels during the menstrual cycle.  In Uganda the factors associated with PMS are hardly documented, making awareness, prevention, and management complicated. The aim of this study, was to determine the social demographic factors associated with PMS among female university students in Central Uganda. Methodology A cross-sectional study was carried out using a self-administered questionnaire between November 2021 and May 2022. 238 female students in 4 universities who consented and met the inclusion criteria participated in the study. Data which was obtained about social demographic characteristics and PMS symptoms was coded and analysed to obtain descriptive statistics and Chi-square correlations.  Results The mean age of the respondents was 22.67±5.595, with most of the respondents (188, 88.7%) being between 19 to 24 years of age, the minimum age was 19 years and the maximum was 55 years. Among this study population, menarche age group χ2(2, n=212) = 7.756, p=0.021, and several menstrual bleeding days χ2(1, n=212) = 5.188, p=0.023 were associated with PMS among the female university students. Conclusion The cause of the PMS among this study population is likely biological as respondents who reported that they started their menses started at age ≤12 years; as well as those whose bleeding days were more than or equal to 5 days were more likely to suffer PMS. Recommendation Studies need to be carried out to investigate the biological causes of PMS to guide management and prevention

Effects and coping mechanisms associated with Premenstrual Syndrome among female University Students in Central Uganda: A Cross-sectional Study

Background The cyclic nature of Premenstrual Syndrome (PMS) affects those with severe symptoms in ways that make them incapacitated or inefficient every month impairing their quality of life. This problem in Uganda is compounded by the cultural stigma associated with menstruation making it difficult for ladies and communities to address the associated problems. Therefore, this study sought to identify how Premenstrual Syndrome affects the quality of life of female University students in Central Uganda in terms of effects and coping mechanisms.  Methodology A cross-sectional study was carried out using a questionnaire between November 2021 and May 2022. 238 participants from 4 universities who met the inclusion criteria were given self-administered questionnaires on PMS symptoms, effects and coping mechanisms. The data was analysed to obtain frequencies and percentages. Statistically significant associations between PMS and Effects of PMS as well as the Coping mechanism were determined using Chi-square correlations. Results At least 70 (33%) of the 212 respondents reported that the PMS symptoms affected either their school and/or their relationships or their daily activities plus home chores. Statistically significant effects of PMS on school efficiency were: sleeping in class χ2(1, n=212) = 4.957, p=0.026; and being late on assignments χ2(1, n=212) = 6.279, p=0.012. Coping mechanisms that were found to be statistically significantly associated with PMS at α-level of 5% were: hiding or locking self in a room χ2(1, n=212) = 4.846, p=0.028; taking alcohol χ2(1, n=212) = 5.115, p=0.024; seeing a health worker χ2(4, n=212) = 14.201, p=0.007; and taking pain killers χ2(1, n=212) = 5.202, p=0.03. Conclusion PMS was significantly affecting school efficiency of students. Recommendation There are still huge knowledge gaps about PMS that need addressing. Some students reported that they used herbal preparations for PMS symptoms which need to be investigated for potential pharmaceutical development

A Novel HLA-A*0201 Restricted Peptide Derived from Cathepsin G Is an Effective Immunotherapeutic Target in Acute Myeloid Leukemia

Immunotherapy targeting aberrantly expressed leukemia associated antigens (LAA) has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely