Financial incentives to improve adherence to anti-psychotic maintenance medication in non-adherent patients - a cluster randomised controlled trial (FIAT)

Background Various interventions have been tested to achieve adherence to anti-psychotic maintenance medication in non-adherent patients with psychotic disorders, and there is no consistent evidence for the effectiveness of any established intervention. The effectiveness of financial incentives in improving adherence to a range of treatments has been demonstrated; no randomised controlled trial however has tested the use of financial incentives to achieve medication adherence for patients with psychotic disorders living in the community. Methods/Design In a cluster randomised controlled trial, 34 mental health teams caring for difficult to engage patients in the community will be randomly allocated to either the intervention group, where patients will be offered a financial incentive for each anti-psychotic depot medication they receive over a 12 month period, or the control group, where all patients will receive treatment as usual. We will recruit 136 patients with psychotic disorders who use these services and who have problems adhering to antipsychotic depot medication, although all conventional methods to achieve adherence have been tried. The primary outcome will be adherence levels, and secondary outcomes are global clinical improvement, number of voluntary and involuntary hospital admissions, number of attempted and completed suicides, incidents of physical violence, number of police arrests, number of days spent in work/training/education, subjective quality of life and satisfaction with medication. We will also establish the cost effectiveness of offering financial incentives. Discussion The study aims to provide new evidence on the effectiveness and cost effectiveness of offering financial incentives to patients with psychotic disorders to adhere to antipsychotic maintenance medication. If financial incentives improve adherence and lead to better health and social outcomes, they may be recommended as one option to improve the treatment of non-adherent patients with psychotic disorders. Trial Registration Current controlled trials ISRCTN77769281

The use of insecticide treated nets by age: implications for universal coverage in Africa

BACKGROUND: The scaling of malaria control to achieve universal coverage requires a better understanding of the population sub-groups that are least protected and provide barriers to interrupted transmission. Here we examine the age pattern of use of insecticide treated nets (ITNs) in Africa in relation to biological vulnerabilities and the implications for future prospects for universal coverage. METHODS: Recent national household survey data for 18 malaria endemic countries in Africa were assembled to identify information on use of ITNs by age and sex. Age-structured medium variant projected population estimates for the mid-point year of the earliest and most recent national surveys were derived to compute the population by age protected by ITNs. RESULTS: All surveys were undertaken between 2005 and 2009, either as demographic health surveys (n = 12) or malaria indicator surveys (n = 6). Countries were categorized into three ITN use groups: or =20% and projected population estimates for the mid-point year of 2007 were computed. In general, the pattern of overall ITNs use with age was similar by country and across the three country groups with ITNs use initially high among children <5 years of age, sharply declining among the population aged 5-19 years, before rising again across the ages 20-44 years and finally decreasing gradually in older ages. For all groups of countries, the highest proportion of the population not protected by ITNs (38% - 42%) was among those aged 5-19 years. CONCLUSION: In malaria-endemic Africa, school-aged children are the least protected with ITNs but represent the greatest reservoir of infections. With increasing school enrollment rates, school-delivery of ITNs should be considered as an approach to reach universal ITNs coverage and improve the likelihood of impacting upon parasite transmission

Decreased availability of antimalarials in the private sector following the policy change from chloroquine to sulphadoxine-pyrimethamine in the Kilombero Valley, Tanzania

BACKGROUND: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. METHODS: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. RESULTS: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment. CONCLUSION: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population

Cross-sectional associations between occupational factors and musculoskeletal pain in women teachers, nurses and sonographers

A. Technical measurements of the physical workload. (DOCX 18 kb

Genome-wide analysis identifies a role for common copy number variants in specific language impairment

An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with population controls, suggesting that CNVs may contribute to SLI risk. A similar trend was observed in first-degree relatives regardless of affection status. The increased burden found in our study was not driven by large or de novo events, which have been described as causative in other neurodevelopmental disorders. Nevertheless, de novo CNVs might be important on a case-by-case basis, as indicated by identification of events affecting relevant genes, such as ACTR2 and CSNK1A1, and small events within known micro-deletion/-duplication syndrome regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs of the independent cases identified significant overrepresentation of acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC proteins as compared with controls. Taken together, our data suggest that the majority of the risk conferred by CNVs in SLI is via common, inherited events within a ‘common disorder–common variant’ model. Therefore the risk conferred by CNVs will depend upon the combination of events inherited (both CNVs and SNPs), the genetic background of the individual and the environmental factors

Methamphetamine Use, Transmission Risk Behavior and Internet Use Among HIV-Infected Patients in Medical Care, San Francisco, 2008

Methamphetamine use is associated with adverse health outcomes and HIV incidence. Few studies have assessed methamphetamine use, sexual behavior and Internet use among HIV-infected patients. Surveys were administered to a sample of HIV-infected patients seeking medical care in a San Francisco county hospital and university-based clinic. In 2008, 35% of homosexual participants, 26% of heterosexual participants and 11% of female participants reported methamphetamine use in the past year. Of participants, 29% reported using the Internet to find sex partners; Internet-users versus non-Internet-users reported a higher median number of sex partners in 6 months (4 vs. 1), were more likely to report unprotected sex (32 vs. 10%), and higher rates of methamphetamine use in the past 12 months (48 vs. 24%). Given the association among methamphetamine use, increased sex partners and Internet use, the Internet may present a new and effective medium for interventions to reduce methamphetamine-associated sexual risk behavior

Proteolysis-Dependent Remodeling of the Tubulin Homolog FtsZ at the Division Septum in \u3ci\u3eEscherichia coli\u3c/i\u3e

During bacterial cell division a dynamic protein structure called the Z-ring assembles at the septum. The major protein in the Z-ring in Escherichia coli is FtsZ, a tubulin homolog that polymerizes with GTP. FtsZ is degraded by the two-component ATP-dependent protease ClpXP. Two regions of FtsZ, located outside of the polymerization domain in the unstructured linker and at the C-terminus, are important for specific recognition and degradation by ClpXP. We engineered a synthetic substrate containing green fluorescent protein (Gfp) fused to an extended FtsZ C-terminal tail (residues 317–383), including the unstructured linker and the C-terminal conserved region, but not the polymerization domain, and showed that it is sufficient to target a non-native substrate for degradation in vitro. To determine if FtsZ degradation regulates Z-ring assembly during division, we expressed a full length Gfp-FtsZ fusion protein in wild type and clp deficient strains and monitored fluorescent Z-rings. In cells deleted for clpX or clpP, or cells expressing protease-defective mutant protein ClpP(S97A), Z-rings appear normal; however, after photobleaching a region of the Z-ring, fluorescence recovers ~70% more slowly in cells without functional ClpXP than in wild type cells. Gfp-FtsZ(R379E), which is defective for degradation by ClpXP, also assembles into Z-rings that recover fluorescence ~2-fold more slowly than Z-rings containing Gfp-FtsZ. In vitro, ClpXP cooperatively degrades and disassembles FtsZ polymers. These results demonstrate that ClpXP is a regulator of Z-ring dynamics and that the regulation is proteolysis-dependent. Our results further show that FtsZ-interacting proteins in E. coli fine-tune Z-ring dynamics

Implementation of an insecticide-treated net subsidy scheme under a public-private partnership for malaria control in Tanzania – challenges in implementation

BACKGROUND: In the past decade there has been increasing visibility of malaria control efforts at the national and international levels. The factors that have enhanced this scenario are the availability of proven interventions such as artemisinin-based combination therapy, the wide scale use of insecticide-treated nets (ITNs) and a renewed emphasis in indoor residual house-spraying. Concurrently, there has been a window of opportunity of financial commitments from organizations such as the Global Fund for HIV/AIDS, Tuberculosis and Malaria (GFATM), the President's Malaria Initiative and the World Bank Booster programme. METHODS: The case study uses the health policy analysis framework to analyse the implementation of a public-private partnership approach embarked upon by the government of Tanzania in malaria control - 'The Tanzania National Voucher Scheme'- and in this synthesis, emphasis is on the challenges faced by the scheme during the pre-implementation (2001 - 2004) and implementation phases (2004 - 2005). Qualitative research tools used include: document review, interview with key informants, stakeholder's analysis, force-field analysis, time line of events, policy characteristic analysis and focus group discussions. The study is also complemented by a cross-sectional survey, which was conducted at the Rufiji Health Demographic Surveillance Site, where a cohort of women of child-bearing age were followed up regarding access and use of ITNs. RESULTS: The major challenges observed include: the re-introduction of taxes on mosquito nets and related products, procurement and tendering procedures in the implementation of the GFATM, and organizational arrangements and free delivery of mosquito nets through a Presidential initiative. CONCLUSION: The lessons gleaned from this synthesis include: (a) the consistency of the stakeholders with a common vision, was an important strength in overcoming obstacles, (b) senior politicians often steered the policy agenda when the policy in question was a 'crisis event', the stakes and the visibility were high, (c) national stakeholders in policy making have an advantage in strengthening alliances with international organizations, where the latter can become extremely influential in solving bottlenecks as the need arises, and (d) conflict can be turned into an opportunity, for example the Presidential initiative has inadvertently provided Tanzania with important lessons in the organization of 'catch-up' campaigns

Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review

BACKGROUND: Malaria is almost invariably ranked as the leading cause of morbidity and mortality in Africa. There is growing evidence of a decline in malaria transmission, morbidity and mortality over the last decades, especially so in East Africa. However, there is still doubt whether this decline is reflected in a reduction of the proportion of malaria among fevers. The objective of this systematic review was to estimate the change in the Proportion of Fevers associated with Plasmodium falciparum parasitaemia (PFPf) over the past 20 years in sub-Saharan Africa. METHODS: Search strategy. In December 2009, publications from the National Library of Medicine database were searched using the combination of 16 MeSH terms.Selection criteria. Inclusion criteria: studies 1) conducted in sub-Saharan Africa, 2) patients presenting with a syndrome of 'presumptive malaria', 3) numerators (number of parasitologically confirmed cases) and denominators (total number of presumptive malaria cases) available, 4) good quality microscopy.Data collection and analysis. The following variables were extracted: parasite presence/absence, total number of patients, age group, year, season, country and setting, clinical inclusion criteria. To assess the dynamic of PFPf over time, the median PFPf was compared between studies published in the years ≤2000 and &gt; 2000. RESULTS: 39 studies conducted between 1986 and 2007 in 16 different African countries were included in the final analysis. When comparing data up to year 2000 (24 studies) with those afterwards (15 studies), there was a clear reduction in the median PFPf from 44% (IQR 31-58%; range 7-81%) to 22% (IQR 13-33%; range 2-77%). This dramatic decline is likely to reflect a true change since stratified analyses including explanatory variables were performed and median PFPfs were always lower after 2000 compared to before. CONCLUSIONS: There was a considerable reduction of the proportion of malaria among fevers over time in Africa. This decline provides evidence for the policy change from presumptive anti-malarial treatment of all children with fever to laboratory diagnosis and treatment upon result. This should insure appropriate care of non-malaria fevers and rationale use of anti-malarials

Working without a blindfold: the critical role of diagnostics in malaria control

Diagnostic testing for malaria has for many years been eschewed, lest it be an obstacle to the delivery of rapid, life-saving treatment. The approach of treating malaria without confirmatory testing has been reinforced by the availability of inexpensive treatment with few side effects, by the great difficulty of establishing quality-assured microscopy in rural and resource-poor settings, and by the preeminence of malaria as a cause of important fever in endemic regions. Within the last decade, all three of these factors have changed. More expensive artemisinin combination therapy (ACT) has been widely introduced, simple immunochromatographic tests for malaria have been developed that can be used as an alternative to microscopy by village health workers, and recognition of the health cost of mismanaging non-malarial fever is growing. In most of the world a small fraction of fever is due to malaria, and reflex treatment with ACT does not make medical or economic sense. Global malaria control efforts have been energized by the availability of new sources of funding, and by the rapid reduction in malaria prevalence in a number of settings where bed nets, indoor residual spraying with insecticides, and ACT have been systematically deployed. This momentum has been captured by a new call for malaria elimination. Without wide implementation of accurate and discriminating diagnostic testing, and reporting of results, most fever will be inappropriately managed, millions of doses of ACT will be wasted, and malaria control programmes will be blindfolded to the impact of their efforts