The Effectiveness and Cost-Effectiveness of Community Diagnostic Centres: A Rapid Review.

Objectives: To examine the effectiveness of community diagnostic centres as a potential solution to increasing capacity and reducing pressure on secondary care in the UK. Methods: A comprehensive search for relevant primary studies was conducted in a range of electronic sources in August 2022. Screening and critical appraisal were undertaken by two independent reviewers. There were no geographical restrictions or limits to year of publication. A narrative synthesis approach was used to analyse data and present findings. Results: Twenty primary studies evaluating twelve individual diagnostic centres were included. Most studies were specific to cancer diagnosis and evaluated diagnostic centres located within hospitals. The evidence of effectiveness appeared mixed. There is evidence to suggest diagnostic centres can reduce various waiting times and reduce pressure on secondary care. However, cost-effectiveness may depend on whether the diagnostic centre is running at full capacity. Most included studies used weak methodologies that may be inadequate to infer effectiveness. Conclusion: Further well-designed, quality research is needed to better understand the effectiveness and cost-effectiveness of community diagnostic centres.

Profiles of tobacco smokers and ex-smokers in a large-scale random sample survey across Wales: an unsupervised machine-learning cluster analysis.

BACKGROUND: The Welsh government recently set a target to be smoke-free by 2030, which means reducing the prevalence of tobacco smoking in adults to 5% by then. The goal is to improve health and population life expectancy. To support this strategy, we identified profile groups with different sets of socioeconomic and demographic characteristics within the population of smokers. We compared these profiles to those identified in the ex-smoker population to provide a broader understanding of smokers and inform targeting of interventions and policy. METHODS: We did a cross-sectional study using data from the National Survey for Wales. This survey is a random sample telephone survey of individuals aged 16 years and older across Wales carried out from Sept 1, 2021 to Jan 31, 2022, weighted to be representative of the Welsh population. For the smoking subgroup, we did a weighted hierarchical cluster analysis with multiple imputation to impute missing data and repeated it for ex-smokers. In total, 63 survey variables were used in the analysis. These variables included smoking history, e-cigarette use, sociodemographics, lifestyle factors, individual-level deprivation, general health and long-term conditions, mental health, and wellbeing. FINDINGS: Among the 6407 respondents (weighted proportions: 49% male, 51% female; 28% aged 16-34 years, 46% aged 35-44 years, 26% aged ≥65 years; 95% white, 5% other ethnicity), 841 (13%) smoked and 2136 (33%) were ex-smokers. Four distinctive profiles of smokers were identified, the groups were of relatively comparable size and characterised by similarities described as (1) high-risk alcohol drinkers and without children; (2) single, mostly in social housing, and poor health and mental health; (3) mostly single, younger, tried e-cigarettes, and poor mental health; (4) older couples and poor health; when comparing the groups with each other. Cluster quality and validation statistics were considered fair: silhouette coefficient=0·09, Dunn index (Dunn2)=1·06. Generally, ex-smoker clusters differed from smoking clusters because of themes related to increased sickness, better affluence, employment, and older age (≥75 years). INTERPRETATION: This study suggests that not all smokers are the same, and they do not fall into one coherent group. Smoking cessation interventions to improve the health of ageing populations might need a different approach to consider a wider context or motivations to inform targeted quitting. It is acknowledged that smoking might be underreported because of perceived social unacceptability. FUNDING: Public Health Wales.

Mapping Inequities in Digital Health Technology Within the World Health Organization's European Region Using PROGRESS PLUS: Scoping Review.

BACKGROUND: The use of digital technologies within health care rapidly increased as services transferred to web-based platforms during the COVID-19 pandemic. Inequalities in digital health across the domains of equity are not routinely examined; yet, the long-term integration of digitally delivered services needs to consider such inequalities to ensure equitable benefits. OBJECTIVE: This scoping review aimed to map inequities in access, use, and engagement with digital health technologies across equity domains. METHODS: We searched 4 electronic databases (MEDLINE, ASSIA, PsycINFO, and Scopus) for quantitative and mixed methods reviews and meta-analyses published between January 2016 and May 2022. Reviews were limited to those that included studies from the World Health Organization's European region. Extracted data were mapped against Cochrane's PROGRESS PLUS (place of residence, race, ethnicity, culture, and language, occupation, gender and sex, religion, education, socioeconomic status, social capital, and other characteristics) dimensions of equity. RESULTS: In total, 404 unique citations were identified from the searches, and 2 citations were identified from other sources. After eligibility assessment, 22 reviews were included. Consistent evidence was found showing higher access to digital health technologies among patients who were of White ethnicity, were English speaking, and had no disability. There were no reviews that explored differences in access to digital health care by age, gender and sex, occupation, education, or homeless or substance misuse. Higher use of digital health technologies was observed among populations that were White, English speaking, younger, with a higher level of education, of higher economic status, and residents in urban areas. No clear evidence of differences in the use of digital technologies by occupation, gender and sex, disability, or homeless or substance misuse was found, nor was clear evidence found in the included reviews on inequalities in the engagement with digital technologies. Finally, no reviews were identified that explored differences by place of residence. CONCLUSIONS: Despite awareness of the potential impact of inequalities in digital health, there are important evidence gaps across multiple equity domains. The development of a common framework for evaluating digital health equity in new health initiatives and consistency in reporting findings is needed.

Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery.

The administration of intermittent parathyroid hormone (iPTH) is anabolic to the skeleton. Recent studies with cultured osteoblasts have revealed that the expression of PHOSPHO1, a bone-specific phosphatase essential for the initiation of mineralisation, is regulated by PTH. Therefore, this study sought to determine whether the bone anabolic response to iPTH involves modulation of expression of Phospho1 and of other enzymes critical for bone matrix mineralisation. To mimic iPTH treatment, primary murine osteoblasts were challenged with 50 nM PTH for 6 h in every 48 h period for 8 days (4 cycles), 14 days (7 cycles) and 20 days (10 cycles) in total. The expression of both Phospho1 and Smpd3 was almost completely inhibited after 4 cycles, whereas 10 cycles were required to stimulate a similar response in Alpl expression. To explore the in vivo role of PHOSPHO1 in PTH-mediated osteogenesis, the effects of 14- and 28-day iPTH (80 µg/kg/day) administration was assessed in male wild-type (WT) and Phospho1-/- mice. The expression of Phospho1, Alpl, Smpd3, Enpp1, Runx2 and Trps1 expression was enhanced in the femora of WT mice following iPTH administration but remained unchanged in the femora of Phospho1-/- mice. After 28 days of iPTH administration, the anabolic response in the femora of WT was greater than that noted in Phospho1-/- mice. Specifically, cortical and trabecular bone volume/total volume, as well as cortical thickness, were increased in femora of iPTH-treated WT but not in iPTH-treated Phospho1-/- mice. Trabecular bone osteoblast number was also increased in iPTH-treated WT mice but not in iPTH-treated Phospho1-/-  mice. The increased levels of Phospho1, Alpl, Enpp1 and Smpd3 in WT mice in response to iPTH administration is consistent with their contribution to the potent anabolic properties of iPTH in bone. Furthermore, as the anabolic response to iPTH was attenuated in mice deficient in PHOSPHO1, this suggests that the osteoanabolic effects of iPTH are at least partly mediated via bone mineralisation processes.

Contribution of avoidable mortality to life expectancy inequalities in Wales: a decomposition by age and by cause between 2002 and 2020.

OBJECTIVES: To explore the contribution of avoidable mortality to life expectancy inequalities in Wales during 2002-2020. DESIGN: Observational study. SETTING: Wales, 2002-20, including early data from the COVID-19 pandemic. METHODS: We used routine statistics for 2002-2020 on population and deaths in Wales stratified by age, sex, deprivation quintile and cause of death. We estimated the contribution of avoidable causes of death and specific age-categories using the Arriaga decomposition method to highlight priorities for action. RESULTS: Life expectancy inequalities rose 2002-20 amongst both sexes, driven by serial decreases in life expectancy amongst the most deprived quintiles. The contributions of amenable and preventable mortality to life expectancy inequalities changed relatively little between 2002 and 2020, with larger rises in non-avoidable causes. Key avoidable mortality conditions driving the life expectancy gap in the most recent period of 2018-2020 for females were circulatory disease, cancers, respiratory disease and alcohol- and drug-related deaths, and also injuries for males. CONCLUSIONS: Life expectancy inequalities widened during 2002-20, driven by deteriorating life expectancy in the most deprived quintiles. Sustained investment in prevention post-COVID-19 is needed to address growing health inequity in Wales; there remains a role for the National Health Service in ensuring equitable healthcare access to alongside wider policies that promote equity.

Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro.

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPIs tested inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73 µM for esomeprazole to 19.27 µM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures was inhibited by several PPIs in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments show for the first time that PPIs inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.

Taking the strain out of onchocerciasis? A reanalysis of blindness and transmission data does not support the existence of a savannah blinding strain of onchocerciasis in West Africa.

Onchocerciasis (also known as 'river blindness'), is a neglected tropical disease (NTD) caused by the (Simulium-transmitted) filarial nematode Onchocerca volvulus. The occurrence of 'blinding' (savannah) and non-blinding (forest) parasite strains and the existence of corresponding, locally adapted Onchocerca-Simulium complexes were postulated to explain greater blindness prevalence in savannah than in forest foci. As a result, the World Health Organization (WHO) Onchocerciasis Control Programme in West Africa (OCP) focused anti-vectorial and anti-parasitic interventions in savannah endemic areas. In this paper, village-level data on blindness prevalence, microfilarial prevalence, and transmission intensity (measured by the annual transmission potential, the number of infective, L3, larvae per person per year) were extracted from 16 West-Central Africa-based publications, and analysed according to habitat (forest, forest-savannah mosaic, savannah) to test the dichotomous strain hypothesis in relation to blindness. When adjusting for sample size, there were no statistically significant differences in blindness prevalence between the habitats (one-way ANOVA, P=0.68, mean prevalence for forest=1.76±0.37 (SE); mosaic=1.49±0.38; savannah=1.89±0.26). The well-known relationship between blindness prevalence and annual transmission potential for savannah habitats was confirmed and shown to hold for (but not to be statistically different from) forest foci (excluding data from southern Côte d'Ivoire, in which blindness prevalence was significantly lower than in other West African forest communities, but which had been the focus of studies leading to the strain-blindness hypothesis that was accepted by OCP planners). We conclude that the evidence for a savannah blinding onchocerciasis strain in simple contrast with a non-blinding forest strain is equivocal. A re-appraisal of the strain hypothesis to explain patterns of ocular disease is needed to improve understanding of onchocerciasis epidemiology and disease burden estimates in the light of the WHO 2030 goals for onchocerciasis.

How bad are life expectancy trends across the UK, and what would it take to get back to previous trends?

BACKGROUND: Within the UK, there has been debate on whether life expectancy is increasing or decreasing in particular single or 3-year periods, but there has been less thinking whether overall trends have changed. This paper considers the extent to which the trends in life expectancy for the UK and its nations have changed before and after 2011. METHODS: We used the Office for National Statistics period life expectancy data for the UK and its nations. We used Lee's approach to project life expectancy based on repeated sampling of year-to-year change in the baseline periods (1990-2011 and 1980-2011) and applied that to 2012 onwards. FINDINGS: Improvements in period life expectancy were substantially and consistently lower between 2012 and 2018 than predicted from the trends from 1980 and, especially, from 1990. By 2018, life expectancy was lower than projected for females and males, respectively, by 1.22 and 1.52 years (England), 1.44 and 0.95 years (Northern Ireland), 1.30 and 1.44 years (Scotland), 1.53 and 1.63 years (Wales) and 1.24 and 1.49 years (UK overall), based on the 1990-2011 baseline period. Using a longer baseline period, which includes the slower rates of improvement during the 1980s, slightly reduces the gap between the current life expectancies and the projected medians. INTERPRETATION: Future academic and policy focus should be on the deviation of the life expectancy trends from the baseline projection rather than on year-to-year variation. Concerted policy focus to return life expectancy to the projected trends is now urgently required.

Is austerity responsible for the recent change in mortality trends across high-income nations? A protocol for an observational study.

INTRODUCTION: Mortality rates in many high-income countries have changed from their long-term trends since around 2011. This paper sets out a protocol for testing the extent to which economic austerity can explain the variance in recent mortality trends across high-income countries. METHODS AND ANALYSIS: This is an ecological natural experiment study, which will use regression adjustment to account for differences in exposure, outcomes and confounding. All high-income countries with available data will be included in the sample. The timing of any changes in the trends for four measures of austerity (the Alesina-Ardagna Fiscal Index, real per capita government expenditure, public social spending and the cyclically adjusted primary balance) will be identified and the cumulative difference in exposure to these measures thereafter will be calculated. These will be regressed against the difference in the mean annual change in life expectancy, mortality rates and lifespan variation compared with the previous trends, with an initial lag of 2 years after the identified change point in the exposure measure. The role of underemployment and individual incomes as outcomes in their own right and as mediating any relationship between austerity and mortality will also be considered. Sensitivity analyses varying the lag period to 0 and 5 years, and adjusting for recession, will be undertaken. ETHICS AND DISSEMINATION: All of the data used for this study are publicly available, aggregated datasets with no individuals identifiable. There is, therefore, no requirement for ethical committee approval for the study. The study will be lodged within the National Health Service research governance system. All results of the study will be published following sharing with partner agencies. No new datasets will be created as part of this work for deposition or curation.

The impact of exercise projects to promote mental wellbeing.

BACKGROUND: There is a well-established link between physical activity and psychological wellbeing, but less evidence on whether it can increase comfort in disclosure of mental health problems and help to reduce the perceived stigma of mental illness. AIMS: To investigate whether exercise projects, funded by the time to change anti-stigma programme to reduce mental health-related stigma and discrimination in England, can improve (1) wellbeing, (2) participation in physical activity, (3) readiness to disclose mental health problems or (4) perceived reduction in levels of stigma and discrimination. METHODS: Participants of exercise projects run in routine community settings by local Mind and Rethink Mental Illness associations completed the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and questions addressing the other three outcomes at baseline and three month follow-up (N = 2663 baseline; N = 531 three month follow-up). RESULTS: There was significant improvement at three months on the WEMWBS (t(386) = -7.64, p = <0.001, r = 0.36); readiness to disclose (χ(2)(1) = 10.86, p = 0.001) and participation in physical activity outside of the project (χ(2)(1) = 12.01, p = 0.001). CONCLUSIONS: Community-based exercise projects have the potential to produce multifaceted positive outcomes for people with mental health problems; however, more methodologically robust studies are needed to adequately determine the effects of exercise.

Mental health problems in the workplace: changes in employers' knowledge, attitudes and practices in England 2006-2010.

BACKGROUND: In 2006 the Shaw Trust charity found high levels of ignorance and poor preparedness to deal with mental health problems among 480 senior employers in the UK. The UK government, non-governmental organisations and Time to Change (TTC) have since provided relevant assistance to employers. AIMS: To examine whether there have been improvements in mental health-related knowledge, attitudes and workplace practices among British senior employers between 2006 and 2010. METHOD: A telephone survey was conducted of senior British employers (n = 480 in 2006 and n = 500 in 2009 and 2010). RESULTS: An increased awareness of common mental health problems was detected. Employers continued to believe that job candidates should disclose a mental health problem, but became less likely to view colleagues' attitudes as a barrier to employing someone with such a problem. Formal policies on mental health and the use of workplace accommodations became increasingly common. CONCLUSIONS: These results are consistent with those of the TTC national public attitudes and the Viewpoint survey of service users between 2008 and 2010, which showed improved public attitudes to mental illness and a reduction in experiences of discrimination in employment.

Influence of Time to Change's social marketing interventions on stigma in England 2009-2011.

BACKGROUND: England's Time To Change (TTC) social marketing campaign emphasised social contact between people with and without mental health problems to reduce stigma and discrimination. AIMS: We aimed to assess the effectiveness of the mass media component and also that of the mass social contact events. METHOD: Online interviews were performed before and after each burst of mass media social marketing to evaluate changes in knowledge, attitudes and behaviour and associations between campaign awareness and outcomes. Participants at social contact events were asked about the occurrence and quality of contact, attitudes, readiness to discuss mental health and intended behaviour towards people with mental health problems. RESULTS: Prompted campaign awareness was 38-64%. A longitudinal improvement was noted for one intended behaviour item but not for knowledge or attitudes. Campaign awareness was positively associated with greater knowledge (ß = 0.80, 95% CI 0.52-1.08) and more favourable attitudes (commonality OR 1.37, 95% CI 1.10-1.70; dangerousness OR 1.41, 95% CI 1.22-1.63) and intended behaviour (ß = 0.75, 95% CI 0.53-0.96). Social contact at events demonstrated a positive impact (M = 2.68) v. no contact (M = 2.42) on perceived attitude change; t(211) = 3.30, P = 0.001. Contact quality predicted more positive attitude change (r = 0.33, P<0.01) and greater confidence to challenge stigma (r = 0.38, P<0.01). CONCLUSIONS: The favourable short-term consequences of the social marketing campaign suggest that social contact can be used by anti-stigma programmes to reduce stigma.

Development and psychometric properties of the Mental Health Knowledge Schedule.

OBJECTIVE: Stigma has been conceptualized as comprised of 3 constructs: knowledge (ignorance), attitudes (prejudice), and behaviour (discrimination). We are not aware of a psychometrically tested instrument to assess knowledge about mental health problems among the general public. Our paper presents the results of the development stage and the psychometric properties of the Mental Health Knowledge Schedule (MAKS), an instrument to assess stigma-related mental health knowledge among the general public. METHODS: We describe the development of the MAKS in addition to 3 studies that were carried out to evaluate the psychometric properties of the MAKS. Adults aged 25 to 45 years in socioeconomic groups: B, C1, and C2 completed the instrument via face-to-face interview (n = 92) and online (n = 403). RESULTS: Internal reliability and test-retest reliability is moderate to substantial. Validity is supported by extensive review by experts (including service users and international experts in stigma research). CONCLUSION: The lack of a valid outcome measure to assess knowledge is a shortcoming of evaluations of stigma interventions and programs. The MAKS was found to be a brief and feasible instrument for assessing and tracking stigma-related mental health knowledge. This instrument should be used in conjunction with other attitude- and behaviour-related measures.

Evaluation of a brief anti-stigma campaign in Cambridge: do short-term campaigns work?

BACKGROUND: In view of the high costs of mass-media campaigns, it is important to understand whether it is possible for a media campaign to have significant population effects over a short period of time. This paper explores this question specifically in reference to stigma and discrimination against people with mental health problems using the Time to Change Cambridge anti-stigma campaign as an example. METHODS: 410 face-to-face interviews were performed pre, during and post campaign activity to assess campaign awareness and mental health-related knowledge, attitudes and behaviours. RESULTS: Although campaign awareness was not sustained following campaign activity, significant and sustained shifts occurred for mental health-related knowledge items. Specifically, there was a 24% (p < 0.001) increase in persons agreeing with the statement: If a friend had a mental health problem, I know what advice to give them to get professional help, following the campaign. Additionally, for the statement: Medication can be an effective treatment for people with mental health problems, there was a 10% rise (p = 0.05) in the proportion of interviewees responding 'agree' or 'strongly agree' following the campaign. These changes, however, were not evident for attitudinal or behaviour related questions. CONCLUSIONS: Although these results only reflect the impact of one small scale campaign, these preliminary findings suggest several considerations for mass-media campaign development and evaluation strategies such as: (1) Aiming to influence outcomes pertaining to knowledge in the short term; (2) Planning realistic and targeted outcomes over the short, medium and long term during sustained campaigns; and (3) Monitoring indirect campaign effects such as social discourse or other social networking/contact in the evaluation.

Employees with mental health problems: Survey of U.K. employers' knowledge, attitudes and workplace practices.

AIM: To investigate whether employers who have experience of hiring people with mental health problems differ significantly from those without such experience in terms of knowledge, attitudes and behaviours regarding mental health in the workplace, and the concerns which they report about employing people with mental health problems. We also examine whether non-workplace social contact is associated with the above variables. METHODS: A telephone survey was conducted with a randomly selected sample of British employers. The sample included a similar number of human resource managers and managers/executive employees in other roles. RESULTS: 502 employers took part. Having employed someone with a mental health problem was associated with closer non-workplace social contact. Those with experience of employing applicants with mental health problems had significant differences in knowledge (regarding the law), and behaviour (having a policy on hiring applicants with disabilities) but not in attitudes. CONCLUSIONS: Non-workplace social contact may be useful to consider in understanding hiring practices. The nature of social contact at work and possible lack of impact of this contact on employer attitudes and concerns warrants further study. Greater support is needed for employers to understand the law regarding mental health problems in the workplace.

Need for timely paediatric HIV treatment within primary health care in rural South Africa.

BACKGROUND: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting. METHODS: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses. FINDINGS: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%. CONCLUSION: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.

Intervention to promote exclusive breast-feeding for the first 6 months of life in a high HIV prevalence area.

OBJECTIVES: We report on a nonrandomized intervention cohort study to increase exclusive breast-feeding rates for 6 months after delivery in HIV-positive and HIV-negative women in KwaZulu-Natal, South Africa. METHODS: Lay counselors visited women to support exclusive breast-feeding: four times antenatally, four times in the first 2 weeks postpartum and then fortnightly to 6 months. Daily feeding practices were collected at weekly intervals by separate field workers. Cumulative exclusive breast-feeding rates from birth were assessed by Kaplan-Meier analysis and association with maternal and infant variables was quantified in a Cox regression analysis. FINDINGS: One thousand, two hundred and nineteen infants of HIV-negative and 1217 infants of HIV-positive women were followed postnatally. Median duration of exclusive breast-feeding was 177 (R = 1-180; interquartile range: 150-180) and 175 days (R = 1-180; interquartile range: 137-180) in HIV-negative and HIV-positive women, respectively. Using 24-h recall, exclusive breast-feeding rates at 3 and 5 months were 83.1 and 76.5%, respectively, in HIV-negative women and 72.5 and 66.7%, respectively, in HIV-positive women. Using the most stringent cumulative data, 45% of HIV-negative and 40% of HIV-positive women adhered to exclusive breast-feeding for 6 months. Counseling visits were strongly associated with adherence to cumulative exclusive breast-feeding at 4 months, those who had received the scheduled number of visits were more than twice as likely to still be exclusively breast-feeding than those who had not (HIV-negative women: adjusted odds ratio: 2.07, 95% confidence interval: 1.56-2.74, P < 0.0001; HIV-positive women: adjusted odds ratio: 2.86, 95% CI 2.13-3.83, P < 0.0001). CONCLUSION: It is feasible to promote and sustain exclusive breast-feeding for 6 months in both HIV-positive and HIV-negative women, with home support from well trained lay counselors.

Surveillance of mother-to-child transmission prevention programmes at immunization clinics: the case for universal screening.

BACKGROUND: Surveillance programmes for prevention of mother-to-child transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections averted, often because of poor postnatal follow-up. Additionally, infected infants are often not identified early and only gain access to comprehensive HIV care and treatment late in their disease. METHODS: Anonymous, unlinked, HIV prevalence testing was conducted on dried blood spot (DBS) samples from all infants attending 6 week immunization clinics at seven primary health care clinics offering PMTCT. Samples were tested for HIV antibodies (indicating maternal HIV infection) and those determined to be from HIV-exposed infants were tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates were determined using birth histories. RESULTS: Samples were collected from 2489 infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95% confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5% of all infants at this age were infected. Amongst mothers who reported that they had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who reported being HIV uninfected but whose infants had HIV antibodies, VTR was 30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births in 1990-1994 to 92/1000 in 2000-2004. CONCLUSIONS: Anonymous HIV prevalence screening of all infants at immunization clinics is feasible to monitor the impact of PMTCT programmes on peripartum infection; linked screening could identify infected children early for referral into care and treatment programmes.

Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study.

BACKGROUND: Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding. METHODS: 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors. FINDINGS: 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birthweight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breastmilk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051). INTERPRETATION: The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.

Estimating the number of vertically HIV-infected children eligible for antiretroviral treatment in resource-limited settings.

BACKGROUND: With the gradual roll-out of antiretroviral therapy (ART) to delay progression of HIV disease in children in programmes across sub-Saharan Africa and resource-limited settings elsewhere, reliable information on the number of vertically infected children eligible for such treatment is urgently required. METHODS: We present a model to estimate the number of vertically HIV-infected children by age who have progressed to moderate to severe disease (MSD) and as such are eligible for ART on the basis of clinical disease, allowing for: antenatal HIV prevalence, use of interventions to prevent mother-to-child transmission (PMTCT), infant feeding policies and availability of co-trimoxazole to prevent opportunistic infections that may hasten the onset of serious disease. The model assumptions were informed by published evidence and expert opinion; rates of progression to serious disease were inferred from mortality of infected and uninfected children of HIV-infected mothers; and mortality among children treated with ART was based on a study of treated children in Abidjan. To allow widespread use the model has been developed using the Excel spreadsheet software. RESULTS: With South Africa as a hypothetical example, published antenatal prevalence and demographic data, and assuming PMTCT coverage with single dose nevirapine of 11%, all exposed and infected children receive co-trimoxazole, and various infant feeding policy scenarios, estimated numbers of children eligible for ART are presented. CONCLUSIONS: This model is easy to implement and flexible and can be used in ART programmes at national and local level.