Antiretroviral therapy in prevention of HIV and TB: update on current research efforts

There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.     

Supporting older people with multimorbidity: The care burden of home health-care assistants in Ireland

The treatment burden inherent in self-managing multiple chronic conditions (multimorbidity) is recognized, but there has been little examination of the care burden experienced by paid home health-care assistants (HCAs) who support older people with multimorbidity. Focus groups were conducted with HCAs in Ireland and data were coded using a thematic analysis approach. Care burden of HCAs was linked with lack of knowledge and information, poor communication, insufficient time and resources, gaps in medication support and work-related stress. Strategies are required to reduce the care burden of HCAs, who are essential stakeholders supporting growing numbers of older people with multimorbidity.     

Final Diagnosis of 112 Girls Presenting With Genital Mucocutaneous Symptoms and Signs: The Mayo Clinic Experience

Pediatric genital mucocutaneous diseases are rare. A retrospective review was performed of children presenting with symptomatology of genital dermatoses to a hospital‐based dermatology service. This study highlights that the range of genital diseases in children is not as broad as in adults. The diagnosis of genital mucocutaneous disease in children is usually genital lichen sclerosus, but other diagnoses should be considered.     

Adjusting for case mix and social class in examining variation in home visits between practices

OBJECTIVES: The purpose of this study was to investigate whether adjusting for clinical case mix and social class explains more of the variation in home visits between general practices than adjusting for age and sex alone. METHODS: The setting was 60 general practices in England and Wales taking part in the 1 year Fourth National Morbidity Survey. The participants comprised 349 505 patients who were registered with one of the participating general practices for at least 180 days, and who had at least one consultation during the period. The outcome measure is whether or not a patient received a home visit in that year. A clinical case mix category (morbidity class) based on 1 year's diagnostic information was assigned to each patient using the Johns Hopkins Adjusted Clinical Groups (ACG) Case Mix System. The social class measure was derived from occupation and employment status and is similar to that of the 1991 UK census. Variations in home visits between practices were examined using multilevel logistic regression models. The variability between practices before and after adjusting for clinical case mix and social class was estimated using the intracluster correlation coefficient (ICC). RESULTS: The overall percentage of patients receiving a home visit over the 1 year study period was 17%, and this varied from 7 to 31% across the 60 practices. The percentage of the total variation in home visits attributable to differences between practices was 2.5% [95% confidence interval (CI) 1.4-3.2%] after adjusting for age and sex. This reduced to 1.6% (95% CI 1.1-2.4%) after taking into account morbidity class. The results were similar when social class was included instead of morbidity class. Morbidity and social class together reduced variation in home visits between practices to 1.5% (95% CI 1.1-2.2%). CONCLUSIONS: Age, sex, social class and clinical case mix are strong determinants of home visits in the UK. Adjusting for morbidity and social class results in a small improvement in explaining the variability in home visits between practices compared with adjusting for age and sex alone. There is far more variation between patients within practices; however, it is not straightforward to examine the factors influencing this variation. In addition to morbidity and social class, there could also be other unmeasured factors such as varying patient demand for home visits, disability or differences in GP home visiting practice style that could influence the large within-practice variability observed in this study.     

Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age

Modulation of neural cell adhesion molecule polysialylation (NCAM PSA) state has been proposed to underlie morphofunctional change associated with consolidation of memory in the rodent, and its age‐dependent decline to be related to impaired cognitive function. To establish whether this may be a human correlate of cognitive decline, we determined the age‐dependent expression of PSA in the human hippocampal dentate gyrus using postmortem tissue derived from individuals who exhibited no obvious neuropathology. As in the rodent, PSA immunoreactivity in the 5‐month human infant was associated mainly with a population of granule‐like cells and their mossy fibre axons. Cell numbers were maximal during the first 3 years of life but declined by an order of magnitude between the second and third decades and remained relatively constant thereafter and was restricted to the granule cell layer/hilar border. In contrast to the rodent, diffuse immunostaining was observed in the inner molecular layer; however, as development advanced, this became relocated to the outer molecular layer from 2 years of age onwards. In addition, numerous polysialylated hilar neurons became evident at 2–3 years of age and remained constant until the eighth decade of life. These findings suggest NCAM polysialylation to play a crucial developmental role within a period concluding with adolescence, and that an attenuated NCAM PSA‐mediated neuroplasticity continues throughout the human lifespan. The importance of the developmental phase of NCAM PSA expression in the emergence of schizophrenia is discussed. J. Neurosci. Res. 55:99–106, 1999. © 1999 Wiley‐Liss, Inc.