The impact of blood transcriptomic biomarker targeted tuberculosis preventive therapy in people living with HIV: a mathematical modelling study

Background Tuberculosis (TB) preventive therapy is recommended for all people living with HIV (PLHIV). Despite the elevated risk of TB amongst PLHIV, most of those eligible for preventive therapy would never develop TB. Tests which can identify individuals at greatest risk of disease would allow more efficient targeting of preventive therapy. Methods We used mathematical modelling to estimate the potential impact of using a blood transcriptomic biomarker (RISK11) to target preventive therapy amongst PLHIV. We compared universal treatment to RISK11 targeted treatment and explored the effect of repeat screening of the population with RISK11. Results Annual RISK11 screening, with preventive therapy provided to those testing positive, could avert 26% (95% CI 13–34) more cases over 10 years compared to one round of universal treatment. For the cost per case averted to be lower than universal treatment, the maximum cost of the RISK11 test was approximately 10% of the cost of preventive therapy. The benefit of RISK11 screening may be greatest amongst PLHIV on ART (compared to ART naïve individuals) due to the increased specificity of the test in this group. Conclusions Biomarker targeted preventive therapy may be more effective than universal treatment amongst PLHIV in high incidence settings but would require repeat screening.

Distinct expression requirements and rescue strategies for BEST1 loss- and gain-of-function mutations

Genetic mutation of the human BEST1 gene, which encodes a Ca2+-activated Cl- channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca2+-dependent Cl- currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that BEST1 patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development, and suggesting that some of the previously classified autosomal dominant mutations actually behave in a dominant-negative manner. Importantly, the strong dominant effect of BEST1 gain-of-function mutations prohibits the restoration of BEST1-dependent Cl- currents in RPE cells by gene augmentation, in contrast to the efficient rescue of loss-of-function mutations via the same approach. Moreover, we demonstrate that gain-of-function mutations are rescuable by a combination of gene augmentation with CRISPR/Cas9-mediated knockdown of endogenous BEST1 expression, providing a universal treatment strategy for all bestrophinopathy patients regardless of their mutation types.

An Affordable and Universal Treatment for ‘Barcode’ Upper Lip Wrinkles

A study was conducted to assess the cost-benefit ratio of manual dermabrasion with an electrocautery scratch pad for upper lip wrinkles. The study included 15 patients with a follow-up ranging from 4 to 108 months. The post-operative course was uneventful without serious complications and all patients were pleased with the results. The mean healing time was 10 to 15 days. The procedure can be performed safely for out-patients with a mean operative time of 30 minutes. The medical supply for the procedure is easily available worldwide and the cost does not exceed 20 euros per patient. It is also a versatile technique that can be performed under local anaesthesia by a surgeon trained with facial nerve blocks. The only drawback is the social exile during the healing time.

Cash Transfer with Turkish Characteristics: Two Local Examples

Having discussed the emergence of cash transfer (CT) as an instrument not only for economic assistance but potentially for inclusion in a market-centered society, and the policy environment of contemporary Turkey, we now bring these together through examination of two case studies of CT programs designed and implemented at the local level. By proceeding in this way, we are explicitly eschewing any claim to providing a universal treatment of social policy, or even of CT programs, in contemporary Turkey. Rather, we consider these cases with a view to highlighting the elements that seem most closely tied to particular outcomes, and then to generalizing these in the form of hypotheses applicable beyond Turkey.

Oral mucositis in patients with oncological pathology of the oropharyngeal region: review

Oral mucositis is one of the most common effects of chemoradiotherapy in patients with oropharyngeal cancer. The development of oral mucositis is the main cause of interruption of antitumor therapy, which significantly affects the results of treatment of the main disease. Despite the fact that the disease is well studied in the literature, today there is no universal treatment and prevention protocol. The aim of this review is to analyze scientific publications devoted to the problems of etiology, pathogenesis, clinic, diagnosis, treatment and prevention of oral mucositis.

Treating infections caused by carbapenemase-producing Enterobacterales (CPE): a pragmatic approach to antimicrobial stewardship on behalf of the UKCPA Pharmacy Infection Network (PIN)

The emergence of carbapenemase-producing Enterobacterales (CPE) as a major cause of invasive infection both within the UK and internationally poses a very real concern for all providers of healthcare. The burden of morbidity and mortality associated with CPE infections is well described. The need for early, targeted, effective and safe antimicrobial therapy remains key for the management of these infected patients yet reliable antimicrobial treatment options remain scarce. In the absence of a universal treatment for these CPE invasive infections, individual treatment options tailored to susceptibilities and severity of infection are required. This working group from within the UK Clinical Pharmacy Association (UKCPA) Pharmacy Infection Network has developed evidence-based treatment recommendations to support infection specialists in managing these complex infections. A systematic review of peer-reviewed research was performed and analysed. We report consensus recommendations for the management of CPE-associated infections. The national expert panel makes therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, dosing, dosage adjustment and monitoring of parameters for novel and established antimicrobial therapies with CPE activity. This manuscript provides the infection specialist with pragmatic and evidence-based options for the management of CPE infections.