Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.

OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART

Cognition in Stroke Rehabilitation and Recovery Research: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabilitation Roundtable (SRRR I), leading to a Cognition Working Group being convened as part of SRRR II. There is currently insufficient evidence to build consensus on specific approaches to cognitive rehabilitation. However, we present recommendations on the integration of cognitive assessments into stroke recovery studies generally and define priorities for ongoing and future research for stroke recovery and rehabilitation. A number of promising interventions are ready to be taken forward to trials to tackle the gap in evidence for cognitive rehabilitation. However, to accelerate progress requires that we coordinate efforts to tackle multiple gaps along the whole translational pathway

Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable

Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabilitation Roundtable (SRRR I), leading to a Cognition Working Group being convened as part of SRRR II. There is currently insufficient evidence to build consensus on specific approaches to cognitive rehabilitation. However, we present recommendations on the integration of cognitive assessments into stroke recovery studies generally and define priorities for ongoing and future research for stroke recovery and rehabilitation. A number of promising interventions are ready to be taken forward to trials to tackle the gap in evidence for cognitive rehabilitation. However, to accelerate progress requires that we coordinate efforts to tackle multiple gaps along the whole translational pathway

PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins

Neurodegenerative diseases are an enormous public health problem, affecting tens of millions of people worldwide. Nearly all of these diseases are characterized by oligomerization and fibrillization of neuronal proteins, and there is great interest in therapeutic targeting of these aggregates. Here, we show that soluble aggregates of α-synuclein and tau bind to plate-immobilized PrP in vitro and on mouse cortical neurons, and that this binding requires at least one of the same N-terminal sites at which soluble Aβ aggregates bind. Moreover, soluble aggregates of tau, α-synuclein and Aβ cause both functional (impairment of LTP) and structural (neuritic dystrophy) compromise and these deficits are absent when PrP is ablated, knocked-down, or when neurons are pre-treated with anti-PrP blocking antibodies. Using an all-human experimental paradigm involving: (1) isogenic iPSC-derived neurons expressing or lacking PRNP, and (2) aqueous extracts from brains of individuals who died with Alzheimer's disease, dementia with Lewy bodies, and Pick's disease, we demonstrate that Aβ, α-synuclein and tau are toxic to neurons in a manner that requires PrPC. These results indicate that PrP is likely to play an important role in a variety of late-life neurodegenerative diseases and that therapeutic targeting of PrP, rather than individual disease proteins, may have more benefit for conditions which involve the aggregation of more than one protein

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY

Towards an understanding of the information and support needs of surgical adolescent idiopathic scoliosis patients: a qualitative analysis

<p>Abstract</p> <p>Background</p> <p>Informed decision making for adolescents and families considering surgery for scoliosis requires essential information, including expected outcomes with or without treatment and the associated risks and benefits of treatment. Ideally families should also receive support in response to their individual concerns. The aim of this study was to identify health-specific needs for online information and support for patients with adolescent idiopathic scoliosis who have had or anticipate having spinal surgery.</p> <p>Methods</p> <p>Focus group methodology was chosen as the primary method of data collection to encourage shared understandings, as well as permit expression of specific, individual views. Participants were considered eligible to participate if they had either experienced or were anticipating surgery for adolescent idiopathic scoliosis within 12 months, were between the ages of 10 and 18 years of age, and were English-speaking.</p> <p>Results</p> <p>Two focus groups consisting of 8 adolescents (1 male, 7 female) and subsequent individual interviews with 3 adolescents (1 male, 2 female) yielded a range of participant concerns, in order of prominence: (1) recovery at home; (2) recovery in hospital; (3) post-surgical appearance; (4) emotional impact of surgery and coping; (5) intrusion of surgery and recovery of daily activities; (6) impact of surgery on school, peer relationships and other social interactions; (7) decision-making about surgery; (8) being in the operating room and; (9) future worries.</p> <p>Conclusion</p> <p>In conclusion, adolescents welcomed the possibility of an accessible, youth-focused website with comprehensive and accurate information that would include the opportunity for health professional-moderated, online peer support.</p

RoB 2: a revised tool for assessing risk of bias in randomised trials

Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool

Patient and provider delay in tuberculosis suspects from communities with a high HIV prevalence in South Africa: A cross-sectional study

BACKGROUND: Delay in the diagnosis of tuberculosis (TB) results in excess morbidity and mortality, particularly among HIV-infected individuals. This study was conducted at a secondary level hospital serving communities with a high HIV prevalence in Cape Town, South Africa. The aim was to describe patient and provider delay in the diagnosis of TB in patients with suspected TB requiring admission, and to determine the risk factors for this delay and the consequences. METHODS: A cross-sectional study was conducted. Patients admitted who were TB suspects were interviewed using a structured questionnaire to assess history of their symptoms and health seeking behaviour. Data regarding TB diagnosis and outcome were obtained from the medical records. Bivariate associations were described using student's T-tests (for means), chi-square tests (for proportions), and Wilcoxon rank-sum tests (for medians). Linear regression models were used for multivariate analysis. RESULTS: One hundred twenty-five (125) patients were interviewed. In 104 TB was diagnosed and these were included in the analysis. Seventy of 83 (84%) tested were HIV-infected. Provider delay (median = 30 days, interquartile range (IQR) = 10.3-60) was double that of patient delay (median = 14 days, IQR = 7-30). Patients had a median of 3 contacts with formal health care services before referral. Factors independently associated with longer patient delay were male gender, cough and first health care visit being to public sector clinic (compared with private general practitioner). Patient delay [greater than or equal to] 14 days was associated with increased need for transfer to a TB hospital. Provider delay [greater than or equal to] 30 days was associated with increased mortality. CONCLUSION: Delay in TB diagnosis was more attributable to provider than patient delay, and provider delay was associated with increased mortality. Interventions to expedite TB diagnosis in primary care need to be developed and evaluated in this setting

Four models of HIV counseling and testing: utilization and test results in South Africa.

BACKGROUND: HIV Counseling and Testing (HCT) is the point-of-entry for pathways of HIV care and prevention. However, HCT is not reaching many who are HIV infected and this may be related to the HCT provision model. We describe HCT utilization and HIV diagnosis using four models of HCT delivery: clinic-based, urban mobile, rural mobile, and stand-alone. METHODS: Using cross-sectional data from routine HCT provided in South Africa, we described client characteristics and HIV test results from information collected during service delivery between January 2009 and June 2012. RESULTS: 118,358 clients received services at clinic-based units, 18,597; stand-alone, 28,937; urban mobile, 38,840; and rural mobile, 31,984. By unit, clients were similar in terms of median age (range 28-31), but differed in sex distribution, employment status, prior testing, and perceived HIV risk. Urban mobile units had the highest proportion of male clients (52%). Rural mobile units reached the highest proportion of clients with no prior HCT (61%) and reporting no perceived HIV risk (64%). Overall, 10,862 clients (9.3%) tested HIV-positive. CONCLUSIONS: Client characteristics varied by HCT model. Importantly, rural and urban mobile units reached more men, first-time testers, and clients who considered themselves to be at low risk for HIV