Preferences for Genetic Testing to Predict the Risk of Developing Hereditary Cancer: A Systematic Review of Discrete Choice Experiments.

BACKGROUND: Understanding service user preferences is key to effective health care decision making and efficient resource allocation. It is of particular importance in the management of high-risk patients in whom predictive genetic testing can alter health outcomes. PURPOSE: This review aims to identify the relative importance and willingness to pay for attributes of genetic testing in hereditary cancer syndromes. DATA SOURCES: Searches were conducted in Medline, Embase, PsycINFO, HMIC, Web of Science, and EconLit using discrete choice experiment (DCE) terms combined with terms related to hereditary cancer syndromes, malignancy synonyms, and genetic testing. STUDY SELECTION: Following independent screening by 3 reviewers, 7 studies fulfilled the inclusion criteria, being a DCE investigating patient or public preferences related to predictive genetic testing for hereditary cancer syndromes. DATA EXTRACTION: Extracted data included study and respondent characteristics, DCE attributes and levels, methods of data analysis and interpretation, and key study findings. DATA SYNTHESIS: Studies covered colorectal, breast, and ovarian cancer syndromes. Results were summarized in a narrative synthesis and the quality assessed using the Lancsar and Louviere framework. LIMITATIONS: This review focuses only on DCE design and testing for hereditary cancer syndromes rather than other complex diseases. Challenges also arose from heterogeneity in attributes and levels. CONCLUSIONS: Test effectiveness and detection rates were consistently important to respondents and thus should be prioritized by policy makers. Accuracy, cost, and wait time, while also important, showed variation between studies, although overall reduction in cost may improve uptake. Patients and the public would be willing to pay for improved detection and clinician over insurance provider involvement. Future studies should seek to contextualize findings by considering the impact of sociodemographic characteristics, health system coverage, and insurance policies on preferences. HIGHLIGHTS: Test effectiveness and detection rates are consistently important to respondents in genetic testing for hereditary cancer syndromes.Reducing the cost of genetic testing for hereditary cancer syndromes may improve uptake.Individuals are most willing to pay for a test that improves detection rates, identifies multiple cancers, and for which results are shared with a doctor rather than with an insurance provider.

What works in interventions targeting loneliness: a systematic review of intervention characteristics.

BACKGROUND: Loneliness has been linked to negative health and economic outcomes across the life course. Health effects span both physical and mental health outcomes, including negative health behaviours, lower well-being, and increased mortality. Loneliness is however preventable with effective intervention. This systematic review aims to identify what has worked in interventions for loneliness to guide the development of future interventions. METHODS: Eight electronic databases (Medline, Embase, PsycINFO, Social Policy and Practice, Social Sciences Citation Index, Epistemonikos, CINAHL, Cochrane Library) were systematically searched from inception to February 2022 using terms for intervention and loneliness to identify relevant interventions in the general population. No restrictions on age, socio-economic status, or geographic location were imposed. Studies were to measure loneliness as the primary outcome through a validated scale or single-item question. Case studies were excluded. Additional studies were identified through citation chasing. Extracted data included study and intervention characteristics, and intervention effectiveness for cross-study comparison. Critical appraisal was conducted using the Joanna Briggs Institute and Critical Appraisal Skills Programme tools before the studies were summarised in a narrative synthesis. RESULTS: Searches identified 4,734 hits, from which 22 studies were included in this review. Of these studies, 14 were effective in reducing loneliness. Additionally, five studies presented unclear findings, and three concluded no decrease in loneliness. Interventions varied between group vs. individual format, online vs. in person delivery, and regarding both intervention duration and individual session length. Furthermore, this review highlighted five key areas when considering designing an intervention for loneliness: use of between session interaction, inclusion of clear learning mechanisms, role of active participation, number of opportunities for group or facilitator interaction, and variation in teaching and learning styles. CONCLUSIONS: Group sessions seem preferred to individual formats, and interaction through active participation and group or facilitator contact appear beneficial, however studies also recognised the importance of a person-tailored approach to delivery. Studies suggest there is no 'quick fix' to loneliness, but that learnt practices, behaviours, and community connection should be built into one's lifestyle to achieve sustained intervention effectiveness. Future interventions should consider longer follow-up periods, male and populations with lower educational levels.

Understanding the effect of loneliness on unemployment: propensity score matching.

BACKGROUND: Loneliness and unemployment are each detrimental to health and well-being. Recent evidence suggests a potential bidirectional relationship between loneliness and unemployment in working age individuals. As most existing research focuses on the outcomes of unemployment, this paper seeks to understand the impact of loneliness on unemployment, potential interaction with physical health, and assess bidirectionality in the working age population. METHODS: This study utilised data from waves 9 (2017-19) and 10 (2018-2020) of the Understanding Society UK Household Longitudinal Study. Nearest-neighbour probit propensity score matching with at least one match was used to infer causality by mimicking randomisation. Analysis was conducted in three steps: propensity score estimation; matching; and stratification. Propensity scores were estimated controlling for age, gender, ethnicity, education, marital status, household composition, number of own children in household and region. Findings were confirmed in panel data random effect models, and heterogeneous treatment effects assessed by the matching-smoothing method. RESULTS: Experience of loneliness in at least one wave increased the probability of being unemployed in wave 10 by 17.5 [95%CI: 14.8, 20.2] percentage points. Subgroup analysis revealed a greater effect from sustained than transitory loneliness. Further exploratory analysis identified a positive average treatment effect, of smaller magnitude, for unemployment on loneliness suggesting bidirectionality in the relationship. The impact of loneliness on unemployment was further exacerbated by interaction with physical health. CONCLUSIONS: This is the first study to directly consider the potentially bidirectional relationship between loneliness and unemployment through analysis of longitudinal data from a representative sample of the working age population. Findings reinforce the need for greater recognition of wider societal impacts of loneliness. Given the persisting and potentially scarring effects of both loneliness and unemployment on health and the economy, prevention of both experiences is key. Decreased loneliness could mitigate unemployment, and employment abate loneliness, which may in turn relate positively to other factors including health and quality of life. Thus, particular attention should be paid to loneliness with additional support from employers and government to improve health and well-being.

Does unemployment lead to greater levels of loneliness? A systematic review.

There is evidence that loneliness and unemployment each have a negative impact on public health. Both are experienced across the life course and are of increasing concern in light of the COVID-19 pandemic. This review seeks to examine the strength and direction of the relationship between loneliness and unemployment in working age individuals, and in particular the potential for a self-reinforcing cycle with combined healthcare outcomes. A systematic search was undertaken in Medline, PubMed, PsycINFO, Embase and EconLit from inception to December 2020. PRISMA reporting guidelines were followed throughout this review, study quality was assessed using the Joanna Briggs Institute checklist and results were summarised in a narrative synthesis. English language studies evaluating the relationship between loneliness and unemployment in higher income western countries were included. Thirty-seven studies were identified; 30 cross-sectional and 7 longitudinal. Loneliness was measured by a direct question or loneliness scale while unemployment was self-reported or retrieved from a national register. A positive association between unemployment and increased loneliness was observed across all studies. Thus, across the life-course a clear yet complex relationship exists between unemployment and greater experience of loneliness. The magnitude of this relationship increases with the severity of loneliness and appears to peak at age 30-34 and 50-59. Logistic regression provided the greatest consistency at statistical significance revealing at least a 40% increase in the likelihood of reporting loneliness when unemployed. Recent longitudinal studies identified in this review found higher levels of loneliness following job loss, but also that loneliness was predictive of unemployment suggesting potential bi-directionality in the relationship. This bi-directionality may create a multiplier effect between loneliness and unemployment to form a self-reinforcing relationship and greater health concerns for those most at risk. Thus, review findings suggest the need for cross-sector awareness and intervention to tackle both loneliness and unemployment.

BabyGel pilot: a pilot cluster randomised trial of the provision of alcohol handgel to postpartum mothers to prevent neonatal and young infant infection-related morbidity in the community.

BACKGROUND: Alcohol-based hand rub (ABHR) is widely used in both health and social facilities to prevent infection, but it is not known whether supplying it for regular perinatal use can prevent newborn sepsis in African rural homes. Our study piloted a cluster randomised trial of providing ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the communities. METHODS: We conducted a pilot parallel cluster randomised controlled trial across ten villages (clusters) in rural Eastern Uganda. Pregnant women of over 34 weeks' gestation were recruited over a period of 3 months. Both clusters received the standard of care of antenatal health education, Maama Kit, and clinic appointments. In addition, women in the intervention villages received ABHR, instructions on ABHR use, a poster on the 'three moments of hand hygiene', and training. We followed up each mother-baby pair for 3 months after birth and measured rates of consent, recruitment, and follow-up (our target rate was more than 80%). Other measures included ABHR use (the acceptable use was more than four times a day) and its mode of distribution (village health workers (VHWs) or pharmacy), acceptability of study protocol and electronic data capture, and the use of WHO Integrated Management of Childhood Illness (IMCI) tool to screen for newborn infection. RESULTS: We selected 36% (10/28) of villages for randomisation to either intervention or control. Over 12 weeks, 176 pregnant women were screened and 58.5% (103/176) were eligible. All, 100% (103/103), eligible women gave consent and were enrolled into the trial (55 intervention and 48 control). After birth, 94.5% (52/55) of mothers in the intervention and 100% (48/48) of mothers in the control villages were followed up within 72 h. Most, 90.9% (50/55), of the mothers in the intervention villages (96.2% of live births) and 95.8% (46/48) of mothers in the control villages (95.9% of live births) were followed up at 3 months. In intervention villages, the average hand rub use was 6.6 times per day. VHWs accounted for all ABHR stock, compared to the pharmacy that could not account for 5 l of ABHR. The screening tool was positive for infection among a third of babies, i.e. 29.2% (14/48) in the intervention villages versus 31.4% (16/51) in the control villages.VHWs completed the first four questions of IMCI screening tool with ease and accuracy. There were no adverse reactions with the ABHR. CONCLUSION: It is feasible to conduct a cluster-randomised controlled trial (cRCT) of the provision of ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the community in resource-poor settings. Our results indicate that home recruitment promotes excellent follow-up and retention of participants in community trials. The intervention was safe. This pilot study informed the substantial changes necessary in the larger cRCT, including a change in the primary outcome to a composite outcome considering multiple methods of infection detection. A large BabyGel cluster randomised controlled trial is now required. TRIAL REGISTRATION: ISRCTN67852437, registered March 02, 2015. TRIAL FUNDING: Medical Research Council/WellcomeTrust/DfID (Global Health Trials Scheme).

In search of a primary outcome for community-based newborn infection trials in Eastern Uganda: a nested cohort study within the BabyGel pilot trial.

BACKGROUND: Due to their immature immune system, neonates are at high risk of infection. This vulnerability when combined with limited resources and health education in developing countries can lead to sepsis, resulting in high global neonatal mortality rates. Many of these deaths are preventable. The BabyGel pilot trial tested the feasibility of conducting the main randomised trial, with the provision of alcohol handgel to postpartum mothers for prevention of neonatal infective morbidity in the rural community. This secondary analysis sought to evaluate the methods of detecting infections in babies up to 3 months of age. METHODS: The pilot two-arm cluster randomised controlled trial took place in 10 villages around Mbale, Eastern Uganda. Women were eligible and recruited antenatally if their gestation was ≥ 34 weeks. All infants of mothers participating in the BabyGel pilot trial were followed up for the first 3 months of life. Evidence for infant infection was collected using five different methods: clinician diagnosed infection, microbiologically confirmed infection, maternally reported infection, a positive infection screen using the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) screening criteria, and reported antibiotic use identified during home and clinic visits. These methods were assessed quantitatively regarding the detection rates of suspected infections and qualitatively by exploring the challenges collecting data in the rural community setting. RESULTS: A total of 103 eligible women participated in the BabyGel pilot trial, with 1 woman delivering twins. Of the 99 mother-infant pairs who consented to participate in the study, 55 infants were identified with infection in total. Maternal report of illness provided the highest estimate, with mothers reporting suspected illness for 45 infants (81.8% of the total suspected infections identified). The WHO IMCI screening criteria identified 30 infants with suspected infection (54.5%), and evidence for antibiotic use was established in 22 infants (40%). Finally, clinician-diagnosed infection identified 19 cases (34.5%), which were also microbiologically confirmed in 5 cases (9.1%). Data collection in the rural setting was hindered by poor communication between mothers and the research team, limited staff awareness of the study in health centres resulting in reduced safeguarding of clinical notes, and widespread use of antibiotics prior to notification and clinical review. Furthermore, identification of suspected infection may not have been limited to severe infections, with ambiguity and no official clinical diagnosis being given to those identified solely by maternal report of infection. CONCLUSIONS: A high rate of suspected infection was identified spanning the five sources of data collection, but no ideal method was found for detection of community neonatal infection. Although maternal self-reports of infant infection provided the highest detection rate, data collection via each source was limited and may have identified minor rather than major infections. Future studies could utilise the IMCI screening tool to detect severe community infection leading to referral for clinical confirmation. This should be combined with weekly contact with mothers to detect maternally suspected illness. Obtaining more details of the symptoms and timescale will improve the accuracy when detecting the total burden of suspected disease, and advising participants to retain medication packaging and prescriptions will improve identification of antibiotic use. TRIAL REGISTRATION: Babygel pilot trial - trial registration: ISCRCTN 67852437. Registered 02/03/2015.

"We have to clean ourselves to ensure that our children are healthy and beautiful": findings from a qualitative assessment of a hand hygiene poster in rural Uganda.

BACKGROUND: Neonatal sepsis is a major cause of mortality worldwide, with most deaths occurring in low-income countries. The World Health Organisation (WHO) '5 Moments for Hand Hygiene' poster has been used to reduce hospital-acquired infections, but there is no similar tool to prevent community-acquired newborn infections in low-resource settings. This assessment, part of the BabyGel Pilot study, evaluated the acceptability of the 'Newborn Moments for Hand Hygiene in the Home' poster. This was an educational tool which aimed to remind mothers in rural Uganda to clean their hands to prevent neonatal infection. METHODS: The BabyGel pilot was a cluster randomised trial that assessed the post-partum use of alcohol-based hand rub (ABHR) to prevent neonatal infections in Mbale, Uganda. Fifty-five women in 5 village clusters received the ABHR and used it from birth to 3 months postnatally, with use guided by the new poster. Following the study, 5 focus group discussions (FGDs) were conducted consisting of 6-8 purposively sampled participants from intervention villages. FGDs were audio-recorded, transcribed then translated into English. Transcripts were inductively coded using ATLAS.ti® and qualitatively analysed using thematic content analysis. RESULTS: Most mothers reported that they understood the message in the poster ("The picture shows me you must use these drugs to keep your baby healthy") and that they could adhere to the moments from the poster. Some participants used the information from the poster to encourage other caregivers to use the ABHR ("after explaining to them, they liked it"). Other potential moments for hand hygiene were introduced by participants, such as after tending to domestic animals and gardening. CONCLUSION: The poster was well-received, and participants reported compliance with the moments for hand hygiene (although the full body wipe of the baby has since been removed). The poster will be adapted into a sticker format on the ABHR bottle. More focus could be put into an education tool for other caregivers who wish to hold the baby. Overall, the study demonstrated the acceptability of an adapted version of the WHO Moments for Hand Hygiene poster in the introduction of an intervention in the community. TRIAL REGISTRATION: ISRCTN67852437 , registered 02/03/2015. TRIAL FUNDING: Medical Research Council/ Wellcome Trust/ DfID (Global Health Trials Scheme).

Optimising informed consent for participants in a randomised controlled trial in rural Uganda: a comparative prospective cohort mixed-methods study.

BACKGROUND: Poor participant understanding of research information can be a problem in community interventional studies with rural African women, whose levels of illiteracy are high. This study aimed to improve the informed consent process for women living in rural eastern Uganda. We assessed the impact of alternative consent models on participants' understanding of clinical trial information and their contribution to the informed consent process in rural Uganda. METHODS: The study applied a parallel mixed-methods design for a prospective comparative cohort, nested within a pilot study on the community distribution of an alcohol-based hand rub to prevent neonatal sepsis (BabyGel pilot trial). Women of at least 34 weeks' pregnancy, suitable for inclusion in the BabyGel pilot trial, were recruited into this study from their homes in 13 villages in Mbale District. As part of the informed consent process, information about the trial was presented using one of three consent methods: standard researcher-read information, a slide show using illustrated text on a flip chart or a video showing the patient information being read as if by a newsreader in either English or the local language. In addition, all women received the patient information sheet in their preferred language. Each information-giving method was used in recruitment for 1 week. Two days after recruitment, women's understanding of the clinical trial was evaluated using the modified Quality of Informed Consent (QuIC) tool. They were also shown the other two methods and their preference assessed using a 5-point Likert scale. Semi-structured interviews were administered to each participant. The interviews were audio-recorded, transcribed and translated verbatim, and thematically analysed. RESULTS: A total of 30 pregnant women in their homes participated in this study. Their recall of the trial information within the planned 48 h was assessed for the majority (90%, 27/30). For all three consent models, women demonstrated a high understanding of the study. There was no statistically significant difference between the slide-show message (mean 4.7; standard deviation, SD 0.47; range 4-5), video message (mean 4.9; SD 0.33; range 4-5) and standard method (mean 4.5; SD 0.53; range 4-5; all one-way ANOVA, p = 0.190). The slide-show message resulted in the most objective understanding of question items with the highest average QuIC score of 100 points. For women who had been recruited using any of the three models, the slide show was the most popular method, with a mean score for all items of not less than 4.2 (mean 4.8; SD 0.6; range 4-5). Most women (63%, 19/30) preferred the slide-show message, compared with 17% (5/30) and 20% (6/30) for the standard and video messages, respectively. The reasons given included the benefits of having pictures to aid understanding and the logical progression of the information. CONCLUSION: Our results from this small study suggest that slide-show messages may be an effective and popular alternative way of presenting trial information to women in rural Uganda, many of whom have little or no literacy. TRIAL REGISTRATION: ISRCTN, ISRCTN67852437 . Registered on 18 March 2018.

Preventing neonatal sepsis in rural Uganda: a cross-over study comparing the tolerance and acceptability of three alcohol-based hand rub formulations.

BACKGROUND: Neonatal sepsis causes 0.5 million deaths annually, mostly in low resource settings. Babies born in African rural homes without running water or toilet facilities are especially vulnerable. Alcohol-based hand rub (ABHR) may be used by mothers and carers as an alternative to hand washing with soap to prevent neonatal infection. However, no definite study has established the preferred formulation of hand rub for the mothers. This study aimed to assess the effects of addition of bitterants and perfume towards the acceptability of the alcohol-based hand rubs by the mothers in their homes after childbirth. METHODS: This was a 3-way blinded cross-over study design. Mothers with children aged ≤3 months were recruited from immunisation clinics at 3 local health facilities in rural eastern Uganda and received 3-different ABHR formulations (in the order plain, bitterant and perfumed) packed in 100 ml bottles. Each ABHR was used for 5 consecutive days followed by a 2-day 'washout' period (evaluation period). Overall satisfaction with each hand rub was evaluated at the end of each week using a 7-point Likert scale. RESULTS: A total of 43 women were recruited, whose ages ranged from 16 to 45 years (mean 26.2 years old). None of the participants normally used a hand protective lotion/cream. The three formulations were used for a mean of 5 (range 3-7) days. A significantly greater volume of the "bitterant" and "perfumed" formulations (mean 91 and 83 ml respectively) were used in comparison to the "plain" formulation (mean 64 ml). Overall satisfaction was high with all the hand rubs, but the perfumed formulation had a significantly higher overall satisfaction score [mean 6.7, range 4-7] compared with the plain [6.4, 3-7] and bitterant [6.2, 2-7] formulations. CONCLUSIONS: All the 3 ABHR formulations were well accepted with little to choose between them. The ABHR with added perfume scored highest on overall satisfaction and was used significantly more often than plain ABHR. ABHR with bitterant additive did, however, score highly and may be a preferable choice to those with concern over alcohol misuse. TRIAL REGISTRATION: ISRCTN67852437 , prospectively registered on 18/03/2018.

Reducing replacement donors in Sub-Saharan Africa: challenges and affordability.

In 1975, the World Health Assembly recommended that blood for transfusion should come from voluntary, non-remunerated donors; yet, in Africa, 75-80% of blood for transfusion still comes from hospital-based replacement donors. Although comprehensive economic data are scarce, evidence indicates that blood from voluntary donors recruited and screened at centralized transfusion centres, costs four to eight times as much as blood from a hospital-based, replacement donor system. Donor recruitment, quality assurance systems and distribution mechanisms in the centralized system are major reasons for the cost difference. There are concerns about the sustainability of centralized voluntary donor systems and their compatibility with the levels of health care that exist in many poor countries yet burdening patients' families with the responsibility of finding replacement blood donors will exacerbate poverty and reduce the safety of the blood supply. There are measures that can be introduced into hospital-based systems to improve safe blood supply in Africa but their effectiveness in different contexts needs to be evaluated.

Evaluation and costs of different haemoglobin methods for use in district hospitals in Malawi.

AIMS: To evaluate the characteristics of manual haemoglobin methods in use in Malawi and provide evidence for the Ministry of Health in Malawi to enable them to choose a suitable method for district hospitals. METHODS: Criteria on accuracy, clinical usefulness, user friendliness, speed, training time, and economic costs were determined by local health professionals and used to compare six different manual haemoglobin methods. These were introduced sequentially into use in a district hospital in Malawi alongside the reference method. RESULTS: HemoCue was the optimal method based on most of the outcome measures but was also the most expensive (0.75 US dollars/test). DHT meter and Jenway colorimeter were the second choice because they were cheaper (0.20-0.35 US dollars/test), but they were not as accurate or user friendly as HemoCue. CONCLUSIONS: The process for choosing appropriate laboratory methods is complex and very little guidance is available for health managers in poorer countries. This paper describes the development and testing of a practical model for gathering evidence about test efficiency that could be adapted for use in other resource poor settings.

Unit costs for house spraying and bednet impregnation with residual insecticides in Colombia: a management tool for the control of vector-borne disease.

A study of unit costs and cost components of two malaria-control strategies (house spraying and bednet impregnation with residual insecticides) was undertaken in 11 malaria-endemic states (departamentos) of Colombia, using data provided by control staff on self-administered questionnaires. The accuracy of the data was verified by personal visits, telephone conversations and complementary information from 10 other states. Allthe financial-cost components of the malaria-control operations carried out in the previous 6 months and the results of the control operations themselves (including the numbers of houses sprayed and numbers of bednets impregnated/day) were recorded. The information was stratified according to whether the target communities were 'near' or 'far away' from an operational base, the far-away communities being those that needed overnight stays by the control staff. The main variables analysed were unit costs/house treated, and annual cost/person protected. The results show that house spraying was generally more expensive for the health services than bednet impregnation. This is particularly the case in 'nearby' communities, where most of those at-risk live. In such communities, spraying one house was 7.2 times more expensive than impregnating one bednet. Even if only those sleeping under an impregnated net were assumed to be protected, the unit costs/person protected in a 'nearby' community were twice as high for house spraying than for bednet impregnation. In 'nearby' communities, where technicians could return to the operational base each evening, insecticides made up 80% of the total spraying costs and 42% of the costs of bednet impregnation. In 'far-away' communities, however, salaries and 'per diems' were the most important cost components, representing, respectively, 23% and 22% of the costs of spraying, and 34% plus 27% of the costs of impregnation. Insecticide wastage and non-use of discounts on insecticide prices (available through the national Ministry of Health) increased the overall costs considerably. The multiple uses of these cost calculations for district health managers are presented.