Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa.

INTRODUCTION: The World Health Organization recommends point-of-care (POC) lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in selected human immunodeficiency virus (HIV) positive people. South Africa had 438 000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive people. LF-LAM is being considered for scale-up in South Africa. METHODS: We estimated the costs of using LF-LAM in HIV-positive adults with CD4 counts 150 cells/μl enrolled in the TB Fast Track Trial in South Africa. We also estimated costs of POC haemoglobin (Hb), as this was used in the study algorithm. Data on clinic-level (10 intervention clinics) and above-clinic-level costs were collected. RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics over 24 months. The mean clinic-level costs were US$12.80 per patient for LF-LAM and POC Hb; LF-LAM costs were US$11.49 per patient. The mean above-clinic-level unit costs for LF-LAM were US$12.06 for clinic preparation, training, coordination and mentoring. The mean total cost of LF-LAM was US$23.55 per patient. CONCLUSION: At clinic level, the cost of LF-LAM was comparable to other TB diagnostics in South Africa. It is important to consider above-clinic-level costs for POC tests, as these may be required to support roll-out and ensure successful implementation

All nonadherence is equal but is some more equal than others? Tuberculosis in the digital era

Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization's recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address nonadherence, as well as offering important information on dose-by-dose adherence patterns and their variability between countries and settings. Previous studies have largely focussed on percentage thresholds to delineate sufficient adherence, but this is misleading and limited, given the complex and dynamic nature of adherence over the treatment course. Instead, we apply a standardised taxonomy – as adopted by the international adherence community – to dose-by-dose medication-taking data, which divides missed doses into 1) late/noninitiation (starting treatment later than expected/not starting), 2) discontinuation (ending treatment early), and 3) suboptimal implementation (intermittent missed doses). Using this taxonomy, we can consider the implications of different forms of nonadherence for intervention and regimen design. For example, can treatment regimens be adapted to increase the “forgiveness” of common patterns of suboptimal implementation to protect against treatment failure and the development of drug resistance? Is it reasonable to treat all missed doses of treatment as equally problematic and equally common when deploying DATs? Can DAT data be used to indicate the patients that need enhanced levels of support during their treatment course? Critically, we pinpoint key areas where knowledge regarding treatment adherence is sparse and impeding scientific progress

Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179

Structural effects induced by dialysis-based purification of carbon nanomaterials

Dialysis plays a crucial role in the purification of nanomaterials but its impact on the structural properties of carbon nanomaterials was never investigated. Herein, a carbon-based nanomaterial generated electrochemically in potassium phosphate buffer, was characterized before and after dialysis against pure water. It is shown that dialysis affects the size of the carbon domains, structural organization, surface functionalization, oxidation degree of carbon, and grade of amorphicity. Accordingly, dialysis drives the nanomaterial organization from discrete roundish carbon domains, with sizes ranging from 70 to 160 nm, towards linear stacking structures of small nanoparticles (<15 ​nm). In parallel, alcohol and ether (epoxide) surface groups evolve into more oxidized carbon groups (e.g., ketone and ester groups). Investigation of the as-prepared nanomaterial by electron paramagnetic resonance (EPR) revealed a resonance signal consistent with carbon-oxygen centred radicals. Additionally, this study brings to light the selective affinity of the carbon nanomaterial under study to capture Na+ ions, a property greatly enhanced by the dialysis process, and its high ability to trap oxygen, particularly before dialysis. These findings open new perspectives for the application of carbon-based nanomaterials and raise awareness of the importance of structural changes that can occur during the purification of carbon-based nanomaterials

The relationship between vitamin D status and muscle strength in young healthy adults from sunny climate countries currently living in the northeast of Scotland

Summary: The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0–3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength.  Introduction: Vitamin D has been suggested to play a role in muscle health and function, but studies so far have been primarily in older populations for falls prevention and subsequent risk of fractures.  Methods: Vitamin D status was assessed in a healthy young adults from sunny climate countries (n = 71, aged 19–42 years) with 56% seen within 3 months of arriving in Aberdeen [newcomers; median (range) time living in the UK = 2 months (9–105 days)] and the remainder resident for >6 months [residents; 23 months (6–121 months)]. Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP). Maximal voluntary contractions (MVC) were performed for grip strength (both arms) and for maximal isometric strength of the knee extensors (right knee).  Results: There were small seasonal variations in 25(OH)D concentrations within the newcomers and residents, but no seasonal variation in bone turnover markers. There was a positive, albeit small, association between 25(OH)D and knee extensor maximal isometric strength. Mixed modelling predicted that for each 1 nmol/L increase in 25(OH)D, peak torque would increase by 1 Nm (p = 0.04).  Conclusions: This study suggests that vitamin D may be important for muscle health in young adults migrating from sunnier climates to high latitudes, yet the potential effect is small

Quality of life assessment as a predictor of survival in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL) in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients.</p> <p>Methods</p> <p>The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL.</p> <p>Results</p> <p>Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10-point increase in global QoL was associated with a 9% increase in survival (95% CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting, insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only physical function (p < 0.001) in previously treated patients were predictive of survival.</p> <p>Conclusions</p> <p>Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.</p

Hunting and Shooting:The Ambiguities of ‘Country Sports’

An introduction to sports shooting as an aspect of animal abuse and the criminal, social and environmental harms - direct, indirect and collateral - associated with the field sports shooting industry

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region