HIV treatment as prevention : models, data, and questions-towards evidence-based decision-making

Antiretroviral therapy (ART) for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to guide policy decisions about the role of ART in reducing HIV incidence. Epidemiology, economics, demography, statistics, biology, and mathematical modelling will be central in framing key decisions in the optimal use of ART. PLoS Medicine, with the HIV Modelling Consortium, has commissioned a set of articles that examine different aspects of HIV treatment as prevention with a forward-looking research agenda. Interlocking themes across these articles are discussed in this introduction. We hope that this article, and others in the collection, will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Topical treatment of peripheral neuropathic pain: applying the evidence

Patients with peripheral neuropathic pain (NP) may only achieve partial pain relief with currently recommended first-line oral treatments, which are also associated with systemic adverse events. Topical treatments are currently considered second- or third-line options, but a recent pharmacologic treatment algorithm has called for broader first-line use of these agents. This has highlighted a need to communicate the benefits associated with topical agents, in particular around the efficacy, targeted local action, and limited systemic availability resulting in minimal systemic adverse events and drug-drug interactions

User involvement and desired service developments in drug treatment: Service user and provider views

Aims - To investigate the existing level of user involvement at selected agencies, to examine views about user involvement from both service-user and provider perspectives and to compare desired service developments. Design/Measurements - As part of a larger project, a series of semi-structured interviews was carried out between 2001 and 2003. Setting - Community-based drug services in Northern England. Participants - Service users (46) and service providers (51). Findings - Overall, the level of service-user involvement was low, with 16% of services having no user involvement at all. Nevertheless, service users expressed a desire for a high level of user involvement, compared with the low aspirations expressed by service providers. Service users' first priority for desired service developments was reduced waiting times, whereas service providers wished for increased provision of complementary therapies. Conclusions - The study highlighted important discrepancies regarding both desired level of user involvement and priorities for service developments between service users und providers. Given the current policies in this field and evidence that user involvement and closer partnerships between users and providers enhances treatment effectiveness, this lack of concurrence might be of major concern and working towards better understanding and balancing users' and providers' needs is highly recommended

Hypomethylating Agents in Treatment of Myelodysplastic Syndrome

Thelkey to the successful treatment of myelodysplastic syndrome is the careful characterization and diagnosis of the disease, which includes clinical, cytogenetic, biological and molecular investigation of individual patients. Today therapeutic approaches to the treatment of such patients are differentiated and depend, first of all, on the subtype of the disease, age, general condition of the patients and the possibility of allogeneic hematopoietic cell transplantation. For young patients, the best option is transplantation, whereas in older patients, the standard of therapy is the use of hypomethylating agents (azacitidine, decitabine). These drugs promote hematologic improvement, elimination of transfusion dependence and prolongation of the duration of both general and leukemia free survival in elderly patients with concomitant pathology.Despite the fact that therapy with hypomethylating drugs is widely used and has good results, many respondents are losing their response within 1–2 years. Reasons for the development of resistance to this type of treatment are still unclear, and the insensitivity to drugs is associated with very poor prognosis in patients with all subtypes of myelodysplastic syndrome. Such data and the presence of numerous genetic and epigenetic mechanisms for the development of this pathology have prompted the use of combinations of drugs with different application points and are relevant in terms of research. In the literature review, the results of clinical studies on the use of hypomethylating agents in patients with MDS of low and high risk, as in monotherapy and combined schemes are presented.The nearest prospect of treatment of myelodysplastic syndrome is the creation of new treatment regimens based on a combination of drugs of different pathogenetic direction for the elimination of the dysplastic clone in order to achieve not only long-term remissions, but also lengthening the duration of overall survival, especially for patients with high risk myelodysplastic syndrome

Efficacy and safety of LDL‐lowering therapy among men and women: meta‐analysis of individual data from 174,000 participants in 27 randomised trials

Background There has been debate about whether statin therapy is as effective in women as men, especially for primary prevention. Methods Meta‐analyses were performed on data from 22 trials of statin therapy vs. control (n=134 537) and five trials of more intensive vs. less intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1∙0 mmol/L reduction in LDL cholesterol and effects in men and women compared using a Cox model that adjusted for non‐gender differences. For subgroup analyses, 99% confidence intervals were used to make allowance for the multiplicity of comparisons. Findings Overall, 46675 (27%) of 174,149 randomised participants were women. Allocation to a statin had similar absolute effects on 1‐year lipid concentrations in both men and women (LDL cholesterol reduced by ~1∙1mmol/L in statin vs. control trials and ~0∙5mmol/L in more vs. less trials). The proportional reductions per 1∙0 mmol/L reduction in LDL cholesterol in major vascular events were similar in women (RR 0∙84, 99% CI 0∙78‐0∙91) and men (RR 0∙78, 99% CI 0∙75‐0∙81), both overall (adjusted p value for heterogeneity by gender=0∙33) and among those at <10% predicted 5‐year risk (adjusted heterogeneity p=0∙11). Likewise, the proportional reductions in major coronary events, coronary revascularisation and stroke did not differ by gender. Since there were similar proportional reductions in vascular mortality in women (RR 0∙92, 99% CI 0∙82‐1∙03) and men (RR 0∙87, 99% CI 0∙82‐0∙92) (adjusted heterogeneity p=0∙84), but no apparent effect on non‐vascular deaths in either sex, all‐cause mortality was reduced in both women (RR 0∙91, 99% CI 0∙84‐0∙99) and men (RR 0∙90, 99% CI 0∙86‐0∙95). Interpretation Other things being equal, statin therapy is of comparable effectiveness for the prevention of major vascular events in women as in men, even among those at low risk of vascular disease