Search

Abstract Introduction Improving menstrual health among schoolgirls is essential to meeting the Sustainable Development Goals (SDGs) of good health and wellbeing (SDG 03), quality education (SDG 04), and gender equality (SDG 05). School participation and wellbeing among girls in low and middle-income countries are impacted by inadequate access to quality menstrual materials and WASH facilities, taboos around menstruation, and poor knowledge. Comprehensive evidence is needed to address these challenges and guide policy and practice. Methods An assisted self-completed questionnaire was used to collect socio-demographic information, menstrual-related data, and school climate data from 486 girls in four mixed-gender government secondary schools in Mwanza, Tanzania. The mean (SD) of three Menstrual Practices and Needs Scale (MPNS-36) sub-scores were calculated. Specifically, the extent to which girls perceived needs for carrying and changing menstrual material in school (transport and school environment); washing and drying menstrual material (reuse needs); and privacy and drying menstrual material in school (reuse insecurity) were met. An ANOVA test compared MPNS scores for groups, and logistic regression examined the association between menstrual health and wellbeing outcomes (self-efficacy, menstrual anxiety, school attendance, and participation) and MPNS subscale scores. Results The mean age of the 486 participants was 15.6 years (SD 1.3); 87% had started menstruating; the mean age at menarche was 14.2 years (SD 1.15). The majority (75%) of girls experienced pain during the last menstrual period, 39% had menstrual-related anxiety, and 16% missed at least one day of school due to menstruation. The mean MPNS subscale score (out of 3) for the reuse needs ranged from 1.0 to 2.1 across schools; 1.6 to 2.1 for reuse insecurity; and 0.9 to 1.8 for transport and school environment needs. The MPNS subscales had sufficient reliability (Cronbach alpha = 0.74 to 0.9). The subscales also had good construct validity with menstrual-related self-efficacy: higher scores for transport and school environment were associated with confidence to seek menstrual support, participate in class, and predict when periods were about to start. Conclusions Schoolgirls have unmet needs related to transporting and using menstrual material in school, and these needs differed across schools in northern Tanzania. Menstrual-related pain remains a major reason for poor school attendance and participation. Interventions to address menstrual practice needs in schools are required and should include a strong pain management component.

IntroductionIn myotonic dystrophy type 2 (DM2), metabolic dysfunctions are frequent. Therefore, measurement of muscle mass and body composition by non-invasive methods could help in evaluating disease severity and progression. The aim of our study was to investigate, by means of bioelectrical impedance analysis (BIA), whether DM2 patients have an alteration in their body composition and if this finding correlates with strength and motor performances.MethodsWe obtained anthropometric measures, nutritional data, BIA and blood tests in 18 DM2 patients and correlated them with motor function tests.ResultsThe 33% of male and 22% of female patients had BMI values compatible with severe obesity, whereas 44% of males and 33% of females had a metabolic syndrome. Considering BIA parameters, phase angle was under normal values in 56% of males and 89% of females. This may be regarded as a marker of deranged cell membrane function. Motor tests showed a fair to strong direct correlation with several BIA parameters.ConclusionThese data suggest that BIA findings may be faithful markers of the degree of muscle wasting and impairment in DM2. The different degree of BIA alterations between genders indicate that body composition undergoes sex-related modifications in this disease. The potential of this technique to capture changes in a slowly progressive disorder such as DM2 should be tested in longitudinal studies.

Abstract Background Structural, interpersonal and individual level factors can present barriers for HIV prevention behaviour among people at high risk of HIV acquisition, including women who sell sex. In this paper we document the contexts in which women selling sex in Kampala meet and provide services to their clients. Methods We collected qualitative data using semi-structured interviews. Women were eligible to participate if they were 18 years or older, self-identified as sex workers or offered sex for money and spoke Luganda or English. Ten women who met clients in venues and outdoor locations were selected randomly from a clinic for women at high risk of HIV acquisition. Ten other women who met clients online were recruited using snowball sampling. Interviews included demographic data, and themes included reasons for joining and leaving sex work, work locations, nature of relationships with clients and peers, interaction with authorities, regulations on sex work, and reported stigma. We conducted interviews over three months. Data were analysed thematically using a framework analysis approach. The coding framework was based on structural factors identified from literature, but also modified inductively with themes arising from the interviews. Results Women met clients in physical and virtual spaces. Physical spaces included venues and outdoor locations, and virtual spaces were online platforms like social media applications and websites. Of the 20 women included, 12 used online platforms to meet clients. Generally, women from the clinic sample were less educated and predominantly unmarried, while those from the snowball sample had more education, had professional jobs, or were university students. Women from both samples reported experiences of stigma, violence from clients and authorities, and challenges accessing health care services due to the illegality of sex work. Even though all participants worked in settings where sex work was illegal and consequently endured harsh treatment, those from the snowball sample faced additional threats of cybersecurity attacks, extortion from clients, and high levels of violence from clients. Conclusions To reduce risk of HIV acquisition among women who sell sex, researchers and implementers should consider these differences in contexts, challenges, and risks to design innovative interventions and programs that reach and include all women.

Abstract Background The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders. We hypothesise that the CHANGE intervention together with enhanced usual care (EUC) will be superior to EUC alone in increasing the percentage of days abstinent. Methods A parallel-arm individually randomised controlled trial will be conducted in the Rhino Camp and Imvepi settlements in Uganda. Five hundred adult male South Sudanese refugees with (i) elevated levels of alcohol use (between 8 and 20 on the Alcohol Use Disorder Identification Test [AUDIT]); and (ii) psychological distress (> 16 on the Kessler Psychological Distress Scale) will be randomly assigned 1:1 to EUC or CHANGE and EUC. CHANGE will be delivered by lay healthcare providers over 6 weeks. Outcomes will be assessed at 3 and 12 months post-randomisation. The primary outcome is the percentage of days abstinent, measured by the timeline follow-back measure at 3 months. Secondary outcomes include percentage of days abstinent at 12 months and alcohol misuse (measured by the AUDIT), psychological distress (i.e. depression, anxiety, posttraumatic stress disorder), functional disability, perpetration of intimate partner violence, and health economic indicators at 3 and 12 months. A mixed-methods process evaluation will investigate competency, dose, fidelity, feasibility, and acceptability. Primary analyses will be intention-to-treat. Discussion CHANGE aims to address alcohol misuse and psychological distress with male refugees in a humanitarian setting. If it is proven to be effective, it can help fill an important under-researched gap in humanitarian service delivery. Trial registration ISRCTN ISRCTN10360385. Registered on 30 January 2023.

Background During adolescence, behaviours are initiated that will have substantial impacts on the individual’s short-term and long-term health and well-being. However, adolescents rarely have regular contact with health services, and available services are not always appropriate for their needs. We co-developed with adolescents a health and well-being check-up programme (Y-Check). This paper describes the methods to evaluate the feasibility, acceptability, short-term effects and cost-effectiveness of Y-Check in three African cities.Method This is a multi-country prospective intervention study, with a mixed-method process evaluation. The intervention involves screening, on-the-spot care and referral of adolescents through health and well-being check-up visits. In each city, 2000 adolescents will be recruited in schools or community venues. Adolescents will be followed-up at 4 months. The study will assess the effects of Y-Check on knowledge and behaviours, as well as clinical outcomes and costs. Process and economic evaluations will investigate acceptability, feasibility, uptake, fidelity and cost effectiveness.Ethics and dissemination Approval has been received from the WHO (WHO/ERC Protocol ID Number ERC.0003778); Ghana Health Service (Protocol ID Number GHS-ERC: 027/07/22), the United Republic of Tanzania National Institute for Medical Research (Clearance No. NIMR/HQ/R.8a/Vol.IX/4199), the Medical Research Council of Zimbabwe (Approval Number MRCZ/A/2766) and the LSHTM (Approval Numbers 26 395 and 28312). Consent and disclosure are addressed in the paper. Results will be published in three country-specific peer-reviewed journal publications, and one multicountry publication; and disseminated through videos, briefs and webinars. Data will be placed into an open access repository. Data will be deidentified and anonymised.Trial registration number NCT06090006.

Abstract Background Preterm birth complications result in > 1 million child deaths annually, mostly in low- and middle-income countries. A World Health Organisation (WHO)-led trial in hospitals with intensive care reported reduced mortality within 28 days among newborns weighing 1000–1799 g who received immediate kangaroo mother care (iKMC) compared to those who received standard care. Evidence is needed regarding the process and costs of implementing iKMC, particularly in non-intensive care settings. Methods We describe actions undertaken to implement iKMC, estimate financial and economic costs of essential resources and infrastructure improvements, and assess readiness for newborn care after these improvements at five Ugandan hospitals participating in the OMWaNA trial. We estimated costs from a health service provider perspective and explored cost drivers and cost variation across hospitals. We assessed readiness to deliver small and sick newborn care (WHO level-2) using a tool developed by Newborn Essential Solutions and Technologies and the United Nations Children’s Fund. Results Following the addition of space to accommodate beds for iKMC, floor space in the neonatal units ranged from 58 m2 to 212 m2. Costs of improvements were lowest at the national referral hospital (financial: $31,354; economic: $45,051; 2020 USD) and varied across the four smaller hospitals (financial: $68,330-$95,796; economic: $99,430-$113,881). In a standardised 20-bed neonatal unit offering a level of care comparable to the four smaller hospitals, the total financial cost could be in the range of $70,000 to $80,000 if an existing space could be repurposed or remodelled, or $95,000 if a new unit needed to be constructed. Even after improvements, the facility assessments demonstrated broad variability in laboratory and pharmacy capacity as well as the availability of essential equipment and supplies. Conclusions These five Ugandan hospitals required substantial resource inputs to allow safe implementation of iKMC. Before widespread scale-up of iKMC, the affordability and efficiency of this investment must be assessed, considering variation in costs across hospitals and levels of care. These findings should help inform planning and budgeting as well as decisions about if, where, and how to implement iKMC, particularly in settings where space, devices, and specialised staff for newborn care are unavailable. Trial registration ClinicalTrials.gov, NCT02811432 . Registered: 23 June 2016.

Abstract Background The vast majority of refugees are hosted in low and middle income countries (LMICs), which are already struggling to finance and achieve universal health coverage for their own populations. While there is mounting evidence of barriers to health care access facing refugees, there is more limited evidence on equity in access to and affordability of care across refugee and host populations. The objective of this study was to examine equity in terms of health needs, service utilisation, and health care payments both within and between South Sudanese refugees and hosts communities (Ugandan nationals), in two districts of Uganda. Methods Participants were recruited from host and refugee villages from Arua and Kiryandongo districts. Twenty host villages and 20 refugee villages were randomly selected from each district, and 30 households were sampled from each village, with a target sample size of 2400 households. The survey measured condition incidence, health care seeking and health care expenditure outcomes related to acute and chronic illness and maternal care. Equity was assessed descriptively in relation to household consumption expenditure quintiles, and using concentration indices and Kakwani indices (for expenditure outcomes). We also measured the incidence of catastrophic health expenditure- payments for healthcare and impoverishment effects of expenditure across wealth quintiles. Results There was higher health need for acute and chronic conditions in wealthier groups, while maternal care need was greater among poorer groups for refugees and hosts. Service coverage for acute, chronic and antenatal care was similar among hosts and refugee communities. However, lower levels of delivery care access for hosts remain. Although maternal care services are now largely affordable in Uganda among the studied communities, and service access is generally pro-poor, the costs of acute and chronic care can be substantial and regressive and are largely responsible for catastrophic expenditures, with service access benefiting wealthier groups. Conclusions Efforts are needed to enhance access among the poorest for acute and chronic care and reduce associated out-of-pocket payments and their impoverishing effects. Further research examining cost drivers and potential financing arrangements to offset these will be important.

Abstract Background Menstrual health is an increasingly recognised public health issue, defined as complete physical, mental, and social well-being in relation to the menstrual cycle. The MENISCUS trial aims to assess whether a multi-component intervention addressing physical and emotional aspects of menstrual health improves educational attainment, mental health problems, menstrual management, self-efficacy, and quality of life among girls in secondary school in Uganda. Methods The study is a parallel-arm cluster-randomised controlled trial with 60 schools (clusters) in Wakiso and Kalungu districts, with a mixed-methods process evaluation to assess intervention fidelity and acceptability and economic and policy analyses. The schools will be randomised 1:1 to immediate intervention or to optimised usual care with delayed intervention delivery. The intervention includes creation of a Menstrual Health Action Group at schools and NGO-led training of trainers on puberty education, development of a drama skit, delivery of a menstrual health kit including reusable pads and menstrual cups, access to pain management strategies including analgesics, and basic improvements to school water, sanitation, and hygiene facilities. Baseline data will be collected from secondary 2 students in 2022 (median age ~15.5 years), with endline after 1 year of intervention delivery (~3600 females and a random sample of ~900 males). The primary outcomes assessed in girls are (i) examination performance based on the Mathematics, English, and Biology curriculum taught during the intervention delivery (independently assessed by the Uganda National Examinations Board) and (ii) mental health problems using the Total Difficulties Scale of the Strengths and Difficulties 25-item questionnaire. Secondary outcomes are menstrual knowledge and attitudes in girls and boys and, in girls only, menstrual practices, self-efficacy in managing menstruation, quality of life and happiness, prevalence of urogenital infections, school and class attendance using a self-completed menstrual daily diary, and confidence in maths and science. Discussion The trial is innovative in evaluating a multi-component school-based menstrual health intervention addressing both physical and emotional aspects of menstrual health and using a “training of trainers” model designed to be sustainable within schools. If found to be cost-effective and acceptable, the intervention will have the potential for national and regional scale-up. Trial registration ISRCTN 45461276 . Registered on 16 September 2021

Castanea sativa Mill. (Cs), a plant traditionally employed in nutrition and to treat various respiratory and gastrointestinal infections, possesses cancer chemopreventive characteristics. In particular, Cs bark extract previously demonstrated antiproliferative and pro-apoptotic activities against a leukemic lymphoblastic cell line. Starting from this evidence, the aim of this paper was to investigate the possibility to affect also the earlier phases of the carcinogenic process by evaluating Cs bark extract’s antimutagenic properties, in particular using the “In Vitro Mammalian Cell Micronucleus Test” on TK6 cells performed by flow cytometry. For this purpose, since an ideal chemopreventive agent should be virtually nontoxic, the first step was to exclude the extract’s genotoxicity. Afterwards, the antimutagenic effect of the extract was evaluated against two known mutagens, the clastogen mitomycin C (MMC) and the aneugen vinblastine (VINB). Our results indicate that Cs bark extract protected cells from MMC-induced damage (micronuclei frequency fold increase reduction from 2.9 to 1.8) but not from VINB. Moreover, we demonstrated that Cs bark extract was a strong antioxidant and significantly reduced MMC-induced ROS levels by over 2 fold. Overall, our research supports the assumption that Cs bark extract can counteract MMC mutagenicity by possibly scavenging ROS production.

Each year, nearly 30 million children globally are at risk of developmental difficulties and disability as a result of newborn health conditions, with the majority living in resource-constrained countries. This study estimates the annual cost to families related to caring for a young child with developmental disability in Uganda. Nested within a feasibility trial of early care and support for young children with developmental disabilities, this sub-study estimated the cost of illness, the cost of paternal abandonment of the caregiver and the affordability of care by household. Seventy-three caregivers took part in this sub-study. The average annual cost of illness to families was USD 949. The main cost drivers were the cost of seeking care and income lost due to loss of employment. Households caring for a child with a disability spent more than the national average household expenditure, and the annual cost of illness for all households was more than 100% of the national GDP per capita. In addition, 84% of caregivers faced economic consequences and resorted to wealth-reducing coping strategies. Families caring for a child with severe impairment incurred USD 358 more on average than those with mild or moderate impairment. Paternal abandonment was common (31%) with affected mothers losing an average of USD 430 in financial support. Caring for a young child with developmental disability was unaffordable to all the study households. Programmes of early care and support have the potential to reduce these financial impacts. National efforts to curb this catastrophic health expenditure are necessary.

Objectives Toilet users often report valuing outcomes such as privacy and safety more highly than reduced disease, but effects of urban sanitation interventions on such outcomes have never been assessed quantitatively. In this study, we evaluate the impact of a shared sanitation intervention on quality of life (QoL) and mental well-being.Design We surveyed individuals living in intervention and control clusters of a recent non-randomised controlled trial, and used generalised linear mixed regression models to make an observational comparison of outcomes between arms.Setting Low-income unsewered areas of Maputo City, Mozambique.Participants We interviewed 424 participants, 222 from the prior trial’s intervention group and 202 from the control group.Interventions The control group used low-quality pit latrines. The intervention group received high-quality shared toilets, with users contributing 10%–15% of capital cost.Outcomes Our primary outcome was the Sanitation-related QoL (SanQoL) index, which applies respondent-derived weights to combine perceptions of sanitation-related disgust, privacy, safety, health and shame. Secondary outcomes were the WHO-5 mental well-being index and a sanitation Visual Analogue Scale.Results The intervention group experienced a 1.6 SD gain in SanQoL compared with the control group. This adjusted SanQoL gain was 0.34 (95% CI 0.29 to 0.38) on a 0–1 scale with control mean 0.49. Effect sizes were largest for safety and privacy attributes. Intervention respondents also experienced a 0.2 SD gain in mental well-being. The adjusted gain was 6.2 (95% CI 0.3 to 12.2) on a 0–100 scale with control mean 54.4.Conclusions QoL outcomes are highly valued by toilet users and can be improved by sanitation interventions. Such outcomes should be measured in future sanitation trials, to help identify interventions which most improve people’s lives. Since SanQoL weights are derived from respondent valuation, our primary result can be used in economic evaluation.

BackgroundEarly care and support provision for young children with developmental disabilities is frequently lacking, yet has potential to improve child and family outcomes, and is crucial for promoting access to healthcare and early education. We evaluated the feasibility, acceptability, early evidence of impact and provider costs of the Baby Ubuntu participatory, peer-facilitated, group program for young children with developmental disabilities and their caregivers in Uganda.Materials and methodsA feasibility trial, with two parallel groups, compared Baby Ubuntu with standard care. Caregivers and children, aged 6–11 months with moderate-severe neurodevelopmental impairment, were recruited and followed for 12 months. Quantitative and qualitative methods captured information on feasibility (ability to recruit), acceptability (satisfactory attendance), preliminary evidence of impact (family quality of life) and provider costs.ResultsOne hundred twenty-six infants (median developmental quotient, 28.7) were recruited and randomized (63 per arm) over 9 months, demonstrating feasibility; 101 (80%) completed the 12-month follow-up assessment (9 died, 12 were lost to follow up, 4 withdrew). Of 63 randomized to the intervention, 59 survived (93%); of these, 51 (86%) attended ≥6 modules meeting acceptability criteria, and 49 (83%) completed the 12 month follow-up assessment. Qualitatively, Baby Ubuntu was feasible and acceptable to caregivers and facilitators. Enabling factors included community sensitization by local champions, positive and caring attitudes of facilitators toward children with disability, peer support, and the participatory approach to learning. Among 101 (86%) surviving children seen at 12 months, mixed methods evaluation provided qualitative evidence of impact on family knowledge, skills, and attitudes, however impact on a scored family quality of life tool was inconclusive. Barriers included stigma and exclusion, poverty, and the need to manage expectations around the child’s progress. Total provider cost for delivering the program per participant was USD 232.ConclusionA pilot feasibility trial of the Baby Ubuntu program found it to be feasible and acceptable to children, caregivers and healthcare workers in Uganda. A mixed methods evaluation provided rich programmatic learning including qualitative, but not quantitative, evidence of impact. The cost estimate represents a feasible intervention for this vulnerable group, encouraging financial sustainability at scale.Clinical trial registration[https://doi.org/10.1186/ISRCTN44380971], identifier [ISRCTN44380971].

Abstract Background An estimated 8–30 % of people living with HIV (PLWH) have depressive disorders (DD) in sub-Saharan Africa. Of these, the majority are untreated in most of HIV care services. There is evidence from low- and middle- income countries of the effectiveness of both psychological treatments and antidepressant medication for the treatment of DD among PLWH, but no evidence on how these can be integrated into routine HIV care. This protocol describes a cluster-randomised trial to evaluate the effectiveness and cost-effectiveness of the HIV + D model for the integration of a collaborative stepped care intervention for DD into routine HIV care, which we have developed and piloted in Uganda. Methods Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts will be randomly selected to participate in the trial. Each facility will recruit 10–30 eligible PLWH with DD and the total sample size will be 1200. The clusters will be randomised 1:1 to receive Enhanced Usual Care alone (EUC, i.e. HIV clinicians trained in Mental Health Gap Action Programme including guidelines on when and where to refer patients for psychiatric care) or EUC plus HIV + D (psychoeducation, Behavioural Activation, antidepressant medication and referral to a supervising mental health worker, delivered in a collaborative care stepwise approach). Eligibility criteria are PLWH attending the clinic, aged ≥ 18 years who screen positive on a depression screening questionnaire (Patient Health Questionnaire, PHQ-9 ≥ 10). The primary outcome is the mean depressive disorder symptom severity scores (assessed using the PHQ-9) at 3 months’ post-randomisation, with secondary mental health, disability, HIV and economic outcomes measured at 3 and 12 months. The cost-effectiveness of EUC with HIV + D will be assessed from both the health system and the societal perspectives by collecting health system, patient and productivity costs and mean DD severity scores at 3 months, additional to health and non-health related quality of life measures (EQ-5D-5 L and OxCAP-MH). Discussion The study findings will inform policy makers and practitioners on the cost-effectiveness of a stepped care approach to integrate depression management in routine care for PLWH in low-resource settings. Trial registration: ISRCTN, ISRCTN86760765. Registered 07 September 2017, https://doi.org/10.1186/ISRCTN86760765 .

Abstract Background It is rare to find HIV/AIDS care providers in sub-Saharan Africa routinely providing mental health services, yet 8–30% of the people living with HIV have depression. In an ongoing trial to assess integration of collaborative care of depression into routine HIV services in Uganda, we will assess quality of life using the standard EQ-5D-5L, and the capability-based OxCAP-MH which has never been adapted nor used in a low-income setting. We present the results of the translation and validation process for cultural and linguistic appropriateness of the OxCAP-MH tool for people living with HIV/AIDS and depression in Uganda. Methods The translation process used the Concept Elaboration document, the source English version of OxCAP-MH, and the Back-Translation Review template as provided during the user registration process of the OxCAP-MH, and adhered to the Translation and Linguistic Validation process of the OxCAP-MH, which was developed following the international principles of good practice for translation as per the International Society for Pharmacoeconomics and Outcomes Research’s standards. Results The final official Luganda version of the OxCAP-MH was obtained following a systematic iterative process, and is equivalent to the English version in content, but key concepts were translated to ensure cultural acceptability, feasibility and comprehension by Luganda-speaking people. Conclusion The newly developed Luganda version of the OxCAP-MH can be used both as an alternative or as an addition to health-related quality of life patient-reported outcome measures in research about people living with HIV with comorbid depression, as well as more broadly for mental health research.

Abstract Background There are 2.5 million neonatal deaths each year; the majority occur within 48 h of birth, before stabilisation. Evidence from 11 trials shows that kangaroo mother care (KMC) significantly reduces mortality in stabilised neonates; however, data on its effect among neonates before stabilisation are lacking. The OMWaNA trial aims to determine the effect of initiating KMC before stabilisation on mortality within seven days relative to standard care. Secondary objectives include exploring pathways for the intervention’s effects and assessing incremental costs and cost-effectiveness between arms. Methods We will conduct a four-centre, open-label, individually randomised, superiority trial in Uganda with two parallel groups: an intervention arm allocated to receive KMC and a control arm receiving standard care. We will enrol 2188 neonates (1094 per arm) for whom the indication for KMC is ‘uncertain’, defined as receiving ≥ 1 therapy (e.g. oxygen). Admitted singleton, twin and triplet neonates (triplet if demise before admission of ≥ 1 baby) weighing ≥ 700–≤ 2000 g and aged ≥ 1–

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects.

BackgroundSchool-based violence prevention interventions offer enormous potential to reduce children's experience of violence perpetrated by teachers, but few have been rigorously evaluated globally and, to the best of our knowledge, none in humanitarian settings. We tested whether the EmpaTeach intervention could reduce physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania.Methods and findingsWe conducted a 2-arm cluster-randomised controlled trial with parallel assignment. A complete sample of all 27 primary and secondary schools in Nyarugusu Refugee Camp were approached and agreed to participate in the study. Eligible students and teachers participated in cross-sectional baseline, midline, and endline surveys in November/December 2018, May/June 2019, and January/February 2020, respectively. Fourteen schools were randomly assigned to receive a violence prevention intervention targeted at teachers implemented in January-March 2019; 13 formed a wait-list control group. The EmpaTeach intervention used empathy-building exercises and group work to equip teachers with self-regulation, alternative discipline techniques, and classroom management strategies. Allocation was not concealed due to the nature of the intervention. The primary outcome was students' self-reported experience of physical violence from teachers, assessed at midline using a modified version of the ISPCAN Child Abuse Screening Tool-Child Institutional. Secondary outcomes included student reports of emotional violence, depressive symptoms, and school attendance. Analyses were by intention to treat, using generalised estimating equations adjusted for stratification factors. No schools left the study. In total, 1,493 of the 1,866 (80%) randomly sampled students approached for participation took part in the baseline survey; at baseline 54.1% of students reported past-week physical violence from school staff. In total, 1,619 of 1,978 students (81.9%) took part in the midline survey, and 1,617 of 2,032 students (79.6%) participated at endline. Prevalence of past-week violence at midline was not statistically different in intervention (408 of 839 students, 48.6%) and control schools (412 of 777 students, 53.0%; risk ratio = 0.91, 95% CI 0.80 to 1.02, p = 0.106). No effect was detected on secondary outcomes. A camp-wide educational policy change during intervention implementation resulted in 14.7% of teachers in the intervention arm receiving a compressed version of the intervention, but exploratory analyses showed no difference in our primary outcome by school-level adherence to the intervention. Main study limitations included the small number of schools in the camp, which limited statistical power to detect small differences between intervention and control groups. We also did not assess the test-retest reliability of our outcome measures, and interviewers were unmasked to intervention allocation.ConclusionsThere was no evidence that the EmpaTeach intervention effectively reduced physical violence from teachers towards primary or secondary school students in Nyarugusu Refugee Camp. Further research is needed to develop and test interventions to prevent teacher violence in humanitarian settings.Trial registrationclinicaltrials.gov (NCT03745573).

Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy.

Cancer affects more than 19 million people and is the second leading cause of death in the world. One of the principal strategies used in cancer therapy is the inhibition of topoisomerase II, involved in the survival of cells. Side effects and adverse reactions limit the use of topoisomerase II inhibitors; hence, research is focused on discovering novel compounds that can inhibit topoisomerase II and have a safer toxicological profile. Marine organisms are a source of secondary metabolites with different pharmacological properties including anticancer activity. The objective of this review is to present and discuss the pharmacological potential of marine-derived compounds whose antitumor activity is mediated by topoisomerase II inhibition. Several compounds derived from sponges, fungi, bacteria, ascidians, and other marine sources have been demonstrated to inhibit topoisomerase II. However, some studies only report docking interactions, whereas others do not fully explain the mechanisms of topoisomerase II inhibition. Further in vitro and in vivo studies are needed, as well as a careful toxicological profile evaluation with a focus on cancer cell selectivity.

BackgroundPsychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor-delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India.Methods and findingsParticipants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor-delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = -0.75, 95% confidence interval [CI] = -1.47, -0.03, p = 0.04; SDQ Total Difficulties: AMD = -1.73, 95% CI = -3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = -0.98, 95% CI = -1.51, -0.45, p < 0.001; SDQ Total Difficulties: AMD = -1.23, 95% CI = -2.37, -0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study's methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes.ConclusionsIn this study, we observed that a lay counselor-delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents' access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up.Trial registrationClinicalTrials.gov NCT03630471.

Abstract Background We aim to test the effectiveness of the EmpaTeach intervention to prevent physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania. EmpaTeach is a 10-week, 14-session, classroom management and cognitive-behavioural therapy-based intervention for groups of teachers for delivery by lay personnel in resource-constrained settings. Methods We will conduct a two-arm cluster randomized controlled trial (RCT) with parallel assignment and an approximately 1:1 allocation ratio. All primary and secondary schools in Nyarugusu will be invited to participate. Whole schools will be stratified according to whether they are Congolese or Burundian, and primary or secondary schools, then randomised to active intervention or wait-list control conditions via a public meeting with headteachers. We will collect survey data from n = 500 teachers and at least n = 1500 students before the intervention, soon after, and at least 6 months after the end of the intervention. The primary outcome measure will be students’ self-reports of experience of physical violence from school staff in the past week, measured using a modified version of the International Society for the Prevention of Child Abuse and Neglect Screening Tool-Child Institutional at the first follow-up after the intervention. Secondary outcomes include emotional violence, depressive symptoms and educational test scores. Analysis will be intention to treat, using repeat cross-sectional data from individuals. Discussion If successful, the EmpaTeach intervention would represent one of a handful of proven interventions to reduce violence from teachers to students in any setting. IRC provides an immediate platform for scale up of the intervention via its current work in more than 40 conflict-affected countries. Trial registration NCT03745573, registered November 19, 2018 at clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03745573.

The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncountable kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the anticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area.

Background: Current guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings. Objective: This paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle-income countries. Design: We describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted. Results: When the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute ‘start-up’ costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams. Conclusions: Given the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data.

Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles. Juglans regia, or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.

In traditional Indian medicine, the crude drug Hemidesmus indicus root—commonly known as Indian sarsaparilla—is used alone or in poly-herbal preparations for the treatment of a wide range of diseases. The present study focuses on the cancer chemopreventive and therapeutic potential of H. indicus extracts on an acute lymphoblastic leukemia cell line (CCRF-CEM). With this aim in mind, we subjected H. indicus roots to two subsequent extractions (hydro-alcoholic extraction and soxhlet extraction). As DNA damage is an important prerequisite for the induction of mutations/cancer by genotoxic carcinogens, cancer chemoprevention may be achieved by preventing genotoxicity. Through an integrated experimental approach, we explored the genoprotective potential of the soxhlet H. indicus extract against different mutagenic compounds and its cytotoxic, proapoptotic, and cytostatic properties. In our experimental conditions, H. indicus induced a cytotoxic effect involving the activation of both intrinsic and extrinsic apoptotic pathways and blocked the cell cycle in the S phase. Moreover, the antigenotoxicity results showed that the extract was able to mitigate DNA damage, an essential mechanism for its applicability as a chemopreventive agent, via either the modulation of extracellular and intracellular events involved in DNA damage. These data add to the growing body of evidence that H. indicus can represent a noteworthy strategy to target early and late stages of cancer.

Background: Tracking of aid resources to reproductive, maternal, newborn, and child health (RMNCH) provides timely and crucial information to hold donors accountable. For the first time, we examine flows in official development assistance (ODA) and grants from the Bill & Melinda Gates Foundation (collectively termed ODA+) in relation to the continuum of care for RMNCH and assess progress since 2003. Methods: We coded and analysed financial disbursements for maternal, newborn, and child health (MNCH) and for reproductive health (R*) to all recipient countries worldwide from all donors reporting to the creditor reporting system database for the years 2011–12. We also included grants from the Bill & Melinda Gates Foundation. We analysed trends for MNCH for the period 2003–12 and for R* for the period 2009–12. Findings: ODA+ to RMNCH from all donors to all countries worldwide amounted to US$12·2 billion in 2011 (an 11·8% increase relative to 2010) and $12·8 billion in 2012 (a 5·0% increase relative to 2011). ODA+ to MNCH represents more than 60% of all aid to RMNCH. ODA+ to projects that have newborns as part of the target population has increased 34-fold since 2003. ODA to RMNCH from the 31 donors, which have reported consistently since 2003, to the 75 Countdown priority countries, saw a 3·2% increase in 2011 relative to 2010 ($8·3 billion in 2011), and an 11·8% increase in 2012 relative to 2011 ($9·3 billion in 2012). ODA to RMNCH projects has increased with time, whereas general budget support has continuously declined. Bilateral agencies are still the predominant source of ODA to RMNCH. Increased funding to family planning, nutrition, and immunisation projects were noted in 2011 and 2012. ODA+ has been targeted to RMNCH during the period 2005–12, although there is no evidence of improvements in targeting over time. Interpretation: Despite a reduction in ODA+ in 2011, ODA+ to RMNCH increased in both 2011 and 2012. The increase in funding is encouraging, but continued increases are needed to accelerate progress towards achieving MDGs 4 and 5 and beyond. Funding: Bill & Melinda Gates Foundation.

Despite widespread implementation across Africa, there is limited evidence of the effect of payment for performance (P4P) schemes in low income countries on the coverage of quality services and affordability, consistent with universal health coverage objectives. We examined the effect of a government P4P scheme on utilisation, quality, and user costs of health services in Tanzania.We evaluated the effects of a P4P scheme on utilisation of all maternal and child immunization services targeted by the scheme, and non-targeted general outpatient service use. We also evaluated effects on patient satisfaction with care and clinical content of antenatal care, and user costs. The evaluation was done in 150 facilities across all 7 intervention districts and 4 comparison districts with two rounds of data collection over 13-months in January 2012 and February 2013. We sampled 3000 households of women who had delivered in the 12 months prior to interview; 1500 patients attending health facilities for targeted and non-targeted services at each round of data collection. Difference-in-difference regression analysis was employed.We estimated a significant positive effect on two out of eight targeted indicators. There was an 8.2% (95% CI: 3.6% to 12.8%) increase in coverage of institutional deliveries among women in the intervention area, and a 10.3% (95% CI: 4.4% to 16.1%) increase in the provision of anti-malarials during pregnancy. Use of non-targeted services reduced at dispensaries by 57.5 visits per month among children under five (95% CI: -110.2 to -4.9) and by 90.8 visits per month for those aged over five (95% CI: -156.5 to -25.2). There was no evidence of an effect of P4P on patient experience of care for targeted services. There was a 0.05 (95% CI: 0.01 to 0.10) increase in the patient satisfaction score for non-targeted services. P4P was associated with a 5.0% reduction in those paying out of pocket for deliveries (95% CI: -9.3% to -0.7%) but there was no evidence of an effect on the average amount paid.This study adds to the very limited evidence on the effects of P4P at scale and highlights the potential risks of such schemes in relation to non-targeted service use. Further consideration of the design of P4P schemes is required to enhance progress towards universal health coverage, and close monitoring of effects on non-targeted services and user costs should be encouraged.