Which aspects of health care are most valued by people living with HIV in high-income countries? A systematic review.

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care.

Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.

Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-kappaB and AP-1. Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1beta treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip-IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs). As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.

Factors associated with non-adherence to oral medication for inflammatory bowel disease: a systematic review.

OBJECTIVES: Adherence is generally associated with improved treatment outcomes. Risk factors for non-adherence must be understood to improve adherence. A systematic review was undertaken to determine which variables were consistently associated with non-adherence to oral medication in inflammatory bowel disease (IBD). METHODS: The databases EMBASE, Medline, and PsycINFO were searched for titles relating to adherence, medication, and IBD (1980-2008). Primary, quantitative studies were included if they concerned adult patients with IBD, measured adherence to oral medication, and measured characteristics associated with adherence. The resulting 17 papers were independently reviewed by two researchers who also assessed their quality according to pre-defined criteria. The main outcome was the frequency with which demographic, clinical, treatment, and psychosocial variables were found to be statistically significantly associated with non-adherence. RESULTS: Non-adherence rates ranged from 7 to 72%, with most studies reporting that 30-45% of patients were non-adherent. No demographic, clinical, or treatment variables were consistently associated with non-adherence. Psychological distress and patients' beliefs about medications were both related to non-adherence in four out of five studies, and doctor-patient discordance was associated with non-adherence in two out of three studies. CONCLUSIONS: This is the largest review of factors associated with non-adherence in IBD. Demographic, clinical, and treatment variables were not consistently associated with non-adherence. Psychological distress, patients' beliefs about medications, and doctor-patient discordance were associated with non-adherence. These findings call into question some of the conclusions of earlier reviews that did not take into account nonsignificant findings. Practical suggestions for gastroenterologists and future research are discussed.

Stem cells and the regulation of proliferation, differentiation and patterning in the intestinal epithelium: emerging insights from gene expression patterns, transgenic and gene ablation studies.

Tissues that undergo self-renewal such as the skin, the haematopoeitic system and the intestine are all maintained and renewed by a small group of multipotent stem cells. The stem cells of the intestinal epithelium are located in the crypts and give rise to its four main lineages located mainly in the finger like projections- the villi. An increasing number of genes are now being identified as either being necessary for or involved in the maintenance of intestinal stem cells and regulating differentiation along the crypt-villus axis. These developmental regulatory genes include among others, Tcf-4, Cdx-1 Fkh6, HFH11 and Nkx2-3. Other genes such as the integrins, and Indian hedgehog (Ihh) also affect function of the progenitor cells of the intestinal epithelium. This mini-review will focus on the more recent data on expression patterns of genes in the intestinal epithelium and the direct or indirect effects of their ablation on proliferation and differentiation.

The IL1 receptor accessory protein is responsible for the recruitment of the interleukin-1 receptor associated kinase to the IL1/IL1 receptor I complex.

Following interleukin-1 (IL1) stimulation, an IL1 receptor associated kinase (IRAK) is rapidly recruited to the receptor complex. However, it is not understood if IRAK is able to interact directly with the intracellular portion of the IL1-RI or if its recruitment is mediated by a different molecule. Using the yeast two-hybrid system, we have analysed possible protein-protein interactions between IRAK, IL1-RI and IL1-RAcP. We found that IRAK is able to interact with the equivalent cytoplasmic region of the IL1-RAcP but is unable to interact with the cytoplasmic region of the IL1-RI. Immunoprecipitation of the IL1-RAcP followed by Western blot analysis using anti-IRAK antibodies revealed that IRAK co-precipitated with the IL1-RAcP. We propose that, in non-stimulated cells, IRAK is bound to the IL1-RAcP and therefore, following IL1 stimulation, both molecules are recruited simultaneously to the ILI-RI complex.

Predicting post-traumatic symptoms in cardiac patients.

OBJECTIVE: The purpose of this study was to identify correlates and predictors of the symptoms of post-traumatic stress disorder (PTSD) in a cohort of patients with myocardial infarction, while the patients were in hospital and 3 months after infarction. DESIGN: Longitudinal, consecutive referrals were used. PATIENTS: From a possible 68 consecutive patients with a first myocardial infarction who completed questionnaires in hospital and survived to 3-month follow-up, 39 completed follow-up questionnaires. OUTCOME MEASURES: PTSD measures were taken in hospital and 3 months after discharge. Predictor variables were measures of mood taken in hospital and measures of the immediate cognitive and emotional reactions at the time of the infarct. RESULTS: Associations between the independent variables and PTSD symptoms were stronger at 3-month follow-up than while in hospital. At this time, the frequency of intrusive thoughts was predicted by the degree of fright at the time of the event (adjusted R(2) = 0.262; beta =.57; t = 3.30; P <.01) and positive affect scores (additional adjusted R(2) = 0.112; beta = -.37 t = -2.18; P <.05). The degree of physiologic arousal at the time of such flashbacks was predicted by levels of negative affect in hospital (adjusted R(2) = 0.174; beta =.46; t = 2.46; P <.05), which also predicted avoidance scores (adjusted R(2) = 0.203; beta =.48; t = 2.62; P <.05). CONCLUSIONS: Because many of the symptoms of PTSD are self-remitting, and intervening too early in the course of the disorder may exacerbate the disorder, it is important not to intervene too early or over-treat this disorder. Formal treatment may be useful if provided some months after discharge from hospital. If either secondary or primary care services are to treat myocardial infarction-related PTSD effectively, it is important to identify patients who are at risk for it. These data contribute to the development of a profile of patients at risk.

An investigation of medication adherence to 5-aminosalicylic acid therapy in patients with ulcerative colitis, using self-report and urinary drug excretion measurements.

BACKGROUND: Non-adherence to 5-aminosalicylic acid (5-ASA) medication can limit the established benefits of this therapy in ulcerative colitis (UC). AIM: To determine rates and predictors of non-adherence to 5-ASA therapy in UC patients. METHODS: Medication adherence was assessed using self-report data and urinary drug excretion measurements. Participants completed a study-specific questionnaire and two validated questionnaires: Beliefs about Medicine Questionnaire (BMQ)-Specific and Satisfaction with Information about Medicines Scale. RESULTS: A total of 169 participants provided self-report adherence data; 151 also provided urine samples. Adherence rates were 111/151 (68%) according to self-report and 90/151 (60%) according to urine analysis, but the two measures were not correlated (chi(2) = 0.12, P = 0.725). Logistic regression identified a significant association between self-reported non-adherence and younger age [odds ratio (OR) for increased age 0.954, 95% confidence interval (CI) 0.932-0.976] and also doubts about personal need for medication (OR for BMQ - Specific Necessity scores 0.578, 95% CI 0.366-0.913). For non-adherence based on urine analysis, only South Asian ethnicity was independently associated with non-adherence (OR 2.940, 95% CI 1.303-6.638). CONCLUSIONS: Our observations confirm the difficulty of accurately assessing medication adherence. Nonmodifiable (younger age, South Asian ethnicity) and potentially modifiable (medication beliefs) predictors of non-adherence were identified.