The whole is greater than the sum of the parts: Recognising missed opportunities for an optimal response to the rapidly maturing TB-HIV co-epidemic in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite widely acknowledged WHO guidelines for the integration of TB and HIV services, heavily burdened countries have been slow to implement these and thus significant missed opportunities have arisen.</p> <p>Discussion</p> <p>The individual-centred, rights-based paradigm of the SA National AIDS Policy, remains dissonant with the compelling public-health approach of TB control. The existence of independent and disconnected TB and HIV services results in a wastage of scarce health resources, an increased burden on patients' time and finances, and ignores evidence of patients' preference for an integrated service. The current situation translates into a web of unacceptable, ongoing missed opportunities such as failure to maximize collaborative disease surveillance, VCT, adherence support, infection control, and positive prevention. TB services present a readily identifiable cohort for HIV provider-initiated testing. Integrating HAART and DOTS will promote efficient usage of health workers' time and a more navigable experience for patients, ultimately ensuring increased TB treatment completion rates and MDR-TB prevention. As direct observation evolves into a more supportive, empowering experience for patients, adherence to both TB drugs and HAART will be bolstered. Little attention has been paid to the transmission of TB within HIV services. Low cost infection control interventions include: triaging patients, scheduling new and follow-up patients separately; well-ventilated, sheltered waiting rooms; and the use of personal respirators by patients and staff. A more patient-centred approach to TB care may be able to recruit the active participation of TB patients in positive prevention efforts, including maximizing personal infection control, limiting exposure of social contacts to TB during the intensive phase of treatment, advocating isoniazid prophylaxis within the home and patient-centred education efforts to reduce overall transmission. Several model programmes demonstrated synergy, in which the impact of the "whole" or integrated response was greater than the sum of the non-integrated parts.</p> <p>Summary</p> <p>The full potential of an integrated TB-HIV service has not been fully harvested. Missed opportunities discount existing efforts in both programmes, will perpetuate the burden of disease, and prevent major gains in future interventions. This paper outlines simple, readily-implementable strategies to narrow the gap and reclaim existing missed opportunities.</p

Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Reliability and concurrent validity of the Dutch hip and knee replacement expectations surveys

Background: Preoperative expectations of outcome of total hip and knee arthroplasty are important determinants of patients' satisfaction and functional outcome. Aims of the study were (1) to translate the Hospital for Special Surgery Hip Replacement Expectations Survey and Knee Replacement Expectations Survey into Dutch and (2) to study test-retest reliability and concurrent validity. Methods: Patients scheduled for total hip (N = 112) or knee replacement (N = 101) were sent the Dutch Expectations Surveys twice with a 2 week interval to determine test-retest reliability. To determine concurrent validity, the Expectation WOMAC was sent. Results: The results for the Dutch Hip Replacement Expectations Survey revealed good test-retest reliability (ICC 0.87), no bias and good internal consistency (alpha 0.86) (N = 72). The correlation between the Hip Expectations Score and the Expectation WOMAC score was 0.59 (N = 86). The results for the Dutch Knee Replacement Expectations Survey revealed good test-retest reliability (ICC 0.79), no bias and good internal consistency (alpha 0.91) (N = 46). The correlation with the Expectation WOMAC score was 0.52 (N = 57). Conclusions: Both Dutch Expectations Surveys are reliable instruments to determine patients' expectations before total hip or knee arthroplasty. As for concurrent validity, the correlation between both surveys and the Expectation WOMAC was moderate confirming that the same construct was determined. However, patients scored systematically lower on the Expectation WOMAC compared to the Dutch Expectation Surveys. Research on patients' expectations before total hip and knee replacement has only been performed in a limited amount of countries. With the Dutch Expectations Surveys it is now possible to determine patients' expectations in another culture and healthcare setting

Service workload patterns for QoS-driven cloud resource management

Cloud service providers negotiate SLAs for customer services they offer based on the reliability of performance and availability of their lower-level platform infrastructure. While availability management is more mature, performance management is less reliable. In order to support a continuous approach that supports the initial static infrastructure configuration as well as dynamic reconfiguration and auto-scaling, an accurate and efficient solution is required. We propose a prediction technique that combines a workload pattern mining approach with a traditional collaborative filtering solution to meet the accuracy and efficiency requirements. Service workload patterns abstract common infrastructure workloads from monitoring logs and act as a part of a first-stage high-performant configuration mechanism before more complex traditional methods are considered. This enhances current reactive rule-based scalability approaches and basic prediction techniques by a hybrid prediction solution. Uncertainty and noise are additional challenges that emerge in multi-layered, often federated cloud architectures. We specifically add log smoothing combined with a fuzzy logic approach to make the prediction solution more robust in the context of these challenges

Comparison of Patient and Surgeon Expectations of Total Hip Arthroplasty

OBJECTIVES: Analysis of discrepancies between patient and surgeon expectations before total hip arthroplasty (THA) should enable a better understanding of motives of dissatisfaction about surgery, but this question has been seldom studied. Our objectives were to compare surgeons' and patients' expectations before THA, and to study factors which affected surgeon-patient agreement. METHODS: 132 adults (mean age 62.8+/-13.7 years, 52% men) on waiting list for THA in three tertiary care centres and their 16 surgeons were interviewed to assess their expectations using the Hospital for Special Surgery Total Hip Replacement Expectations Survey (range 0-100). Patients' and surgeons' answers were compared, for the total score and for the score of each item. Univariate analyses tested the effect of patients' characteristics on surgeons' and patients' expectations separately, and on surgeon-patient differences. RESULTS: Surgeon and patient expectations' mean scores were high (respectively 90.9+/-11.1 and 90.0+/-11.6 over 100). Surgeons' and patients' expectations showed no systematic difference, but there was little agreement on Bland and Altman graph and correlation coefficient was low. Patients had higher expectations than surgeons for sports. Patients rated their expectations according to trust in physician and mental quality of life, surgeons considered disability. More disabled patients and patients from a low-income professional category were often "more optimistic" than their surgeons. CONCLUSION: Surgeons and patients often do not agree on what to expect from THA. More disabled patients expect better outcomes than their surgeons

Stiffness in total knee arthroplasty

Stiffness is a relatively uncommon complication after total knee arthroplasty. It has been defined as a painful limitation in the range of movement (ROM). Its pathogenesis is still unclear even if some risk factors have been identified. Patient-related conditions may be difficult to treat. Preoperative ROM is the most important risk factor, but an association with diabetes, reflex sympathetic dystrophy, and general pathologies such as juvenile rheumatoid arthritis and ankylosing spondylitis has been demonstrated. Moreover, previous surgery may be an additional cause of an ROM limitation. Postoperative factors include infections, arthrofibrosis, heterotrophic ossifications, and incorrect rehabilitation protocol. Infections represent a challenging problem for the orthopaedic surgeon, and treatment may require long periods of antibiotics administration. However, it is widely accepted that an aggressive rehabilitation protocol is mandatory for a proper ROM recovery and to avoid the onset of arthrofibrosis and heterotrophic ossifications. Finally, surgery-related factors represent the most common cause of stiffness; they include errors in soft-tissue balancing, component malpositioning, and incorrect component sizing. Although closed manipulation, arthroscopic and open arthrolysis have been proposed, they may lead to unpredictable results and incomplete ROM recovery. Revision surgery must be proposed in the case of well-documented surgical errors. These operations are technically demanding and may be associated with high risk of complications; therefore they should be accurately planned and properly performed

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at 16q11.2 and MAPT H1 loci.

Parkinson's disease is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies has considerably advanced our understanding of the Parkinson's disease genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Impaired mitophagy is a key causative pathway in familial Parkinson's disease, but its relevance to idiopathic Parkinson's disease is unclear. We used a mitophagy screening assay to evaluate the functional significance of risk genes identified through genome-wide association studies. We identified two new regulators of PINK1-dependent mitophagy initiation, KAT8 and KANSL1, previously shown to modulate lysine acetylation. These findings suggest PINK1-mitophagy is a contributing factor to idiopathic Parkinson's disease. KANSL1 is located on chromosome 17q21 where the risk associated gene has long been considered to be MAPT. While our data does not exclude a possible association between the MAPT gene and Parkinson's disease, it provides strong evidence that KANSL1 plays a crucial role in the disease. Finally, these results enrich our understanding of physiological events regulating mitophagy and establish a novel pathway for drug targeting in neurodegeneration