Classifying new anti-tuberculosis drugs: Rationale and future perspectives

The classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2-5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed

The frequency of HLA-B*57:01 and the risk of Abacavir hypersensitivity reactions in the Costa Rica Central Valley Population

HLA-B*57:01 is a pharmacogenetic marker for abacavir hypersensitivity among HIV+ individuals. The utility and cost-effectiveness of the typing of this allele as a prospective marker has been confirmed to decrease or abolish abacavir hypersensitivity reactions in these patients. However, as for other HLA alleles, there is widespread variation in its frequency across populations. Thus, characterisation of the frequency of this marker in a given population is the first step towards the evaluation of the feasibility and need of pharmacogenetic screening for this drug. The Costa Rica Central Valley Population (CCVP) is the major population in this country. The frequency of HLA-B*57:01 in this population has not been described yet. Consequently, in an exploratory study, we set out to determine the frequency of this allele in a sample of unrelated healthy blood donors. We genotyped 153 samples from CCVP inhabitants. The samples were typed to intermediate resolution by SSO or SSP methods, and samples that were HLA-B*57-positve were further typed by sequence- based typing in order to define the alleles to four-digit resolution. An HLA-B*57:01 carrier frequency of 5.23% (allele frequency of 2.61%) was determined in this sample. This frequency is relatively high in comparison to reports from other populations in Latin America. These results suggest that there is a considerable frequency of HLA-B*57:01 in the CCVP and that pharmacogenetic testing for HIV+ patients who are going to receive abacavir-based treatment schemes is likely to benefit the security of this therapy. According to WHO data, we hypothesize that some 200,000 persons in this country would be susceptible to abacavir- induced hypersensitivity, and that some 15,000 HIV+ people living in Costa Rica could benefit from prospective HLA-B*57:01 genotyping

Estimating internationally imported cases during the early COVID-19 pandemic

Early in the COVID-19 pandemic, predictions of international outbreaks were largely based on imported cases from Wuhan, China, potentially missing imports from other cities. We provide a method, combining daily COVID-19 prevalence and flight passenger volume, to estimate importations from 18 Chinese cities to 43 international destinations, including 26 in Africa. Global case importations from China in early January came primarily from Wuhan, but the inferred source shifted to other cities in mid-February, especially for importations to African destinations. We estimate that 10.4 (6.2 - 27.1) COVID-19 cases were imported to these African destinations, which exhibited marked variation in their magnitude and main sources of importation. We estimate that 90% of imported cases arrived between 17 January and 7 February, prior to the first case detections. Our results highlight the dynamic role of source locations, which can help focus surveillance and response efforts

Thermal diffusivity, effusivity and conductivity of CdMnTe mixed crystals

Cd1-xMnxTe mixed crystals belong to a class of materials called ‘‘semimagnetic semiconductor’’ or diluted magnetic semiconductor (DMS) with addition of magnetic ions like Mn2+ implemented into crystal structure. The crystals under investigation were grown from the melt by the high pressure high temperature modified Bridgman method in the range of composition 0 < x < 0.7. Thermal properties of these compounds have been investigated by means of photopyroelectric (PPE) calorimetry in both, back and front detection configuration. The values of the thermal diffusivity and effusivity were derived from experimental data. Thermal conductivity of the specimens was calculated from the simple theoretical dependencies between thermal parameters. The influence of Mn concentration on thermal properties of Cd1-xMnxTe crystals have been presented and discussed

Vestibular schwannoma with contralateral facial pain – case report

BACKGROUND: Vestibular schwannoma (acoustic neuroma) most commonly presents with ipsilateral disturbances of acoustic, vestibular, trigeminal and facial nerves. Presentation of vestibular schwannoma with contralateral facial pain is quite uncommon. CASE PRESENTATION: Among 156 cases of operated vestibular schwannoma, we found one case with unusual presentation of contralateral hemifacial pain. CONCLUSION: The presentation of contralateral facial pain in the vestibular schwannoma is rare. It seems that displacement and distortion of the brainstem and compression of the contralateral trigeminal nerve in Meckel's cave by the large mass lesion may lead to this atypical presentation. The best practice in these patients is removal of the tumour, although persistent contralateral pain after operation has been reported

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area

Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy

Latent Class Analysis of Sexual Risk Patterns Among Esquineros (Street Corner Men) a Group of Heterosexually Identified, Socially Marginalized Men in Urban Coastal Peru

We explored patterns of sexual risk behavior among esquineros, heterosexually-identified, socially-marginalized Peruvian men using latent class analysis. We used data from the Peru site of the National Institute of Mental Health (NIMH) Collaborative HIV/STD Prevention Trial which included n = 2,109 heterosexually-identified men. The latent class analysis used seven risk behaviors to group esquineros into risk classes. We identified four latent classes, of which two classes had lower probabilities and two classes had higher probabilities of these risk behaviors. Comparing the two lower risk classes to the two higher risk classes yielded significantly more unprotected sex acts (Chi square P value < 0.001). The risk behaviors in two of the latent classes identified were primarily related to alcohol and drug use. Future HIV/STI prevention interventions may benefit from this information by tailoring messages to fit the observed risk patterns and should focus on drug and alcohol use

Decomposition techniques with mixed integer programming and heuristics for home healthcare planning

We tackle home healthcare planning scenarios in the UK using decomposition methods that incorporate mixed integer programming solvers and heuristics. Home healthcare planning is a difficult problem that integrates aspects from scheduling and routing. Solving real-world size instances of these problems still presents a significant challenge to modern exact optimization solvers. Nevertheless, we propose decomposition techniques to harness the power of such solvers while still offering a practical approach to produce high-quality solutions to real-world problem instances. We first decompose the problem into several smaller sub-problems. Next, mixed integer programming and/or heuristics are used to tackle the sub-problems. Finally, the sub-problem solutions are combined into a single valid solution for the whole problem. The different decomposition methods differ in the way in which subproblems are generated and the way in which conflicting assignments are tackled (i.e. avoided or repaired). We present the results obtained by the proposed decomposition methods and compare them to solutions obtained with other methods. In addition, we conduct a study that reveals how the different steps in the proposed method contribute to those results. The main contribution of this paper is a better understanding of effective ways to combine mixed integer programming within effective decomposition methods to solve real-world instances of home healthcare planning problems in practical computation time

Inter-cellular forces orchestrate contact inhibition of locomotion.

Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors