Garciaputnam0480

High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity.

In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events.

We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46-56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P<0.001). In CSF, standard-of-8-fold higher than standard-of-care, and CSF levels above the MIC.In the March issue of BJS several hot topics within the breast surgery field are highlighted in beautifully planned and executed prospective multicentre trials. BJS encourages the surgical communities in most fields to move towards prospective collaborative and multicentre studies, thereby increasing both power and generalizability as well as reducing the risk of bias.Peripheral inflammation is always accompanied by a noxious sensation, either pain or itch, providing a protective warning for the occurrence of pathological changes; however, the mechanisms determining whether pain, itch, or both will be elicited under certain inflammatory statuses are still far from clear. Complete Freund's adjuvant (CFA) contains heat killed and dried Mycobacterium tuberculosis widely used to induce inflammatory pain models, but how CFA treatment affects itch sensation and the possible mechanisms are still unclear. In this study, using itch behavior testing and calcium imaging, we showed that both the behaviors and calcium responses associated with Transient Receptor Potential Vanilloid 1 (TRPV1)-mediated histamine-dependent itch and Transient Receptor Potential Ankyrin 1 (TRPA1)-mediated histamine-independent itch were significantly suppressed by CFA treatment. Furthermore, to explore the possible cellular mechanisms, high-throughput single-cell RNA sequencing and real-time PCR were used to detect CFA-induced changes of itch-related genes in dorsal root ganglion (DRG) neurons. Our results revealed that although both nociceptive Trpv1+ and Trpa1+ DRG neurons were increased after CFA treatment, most known pruriceptors, including Hrh1+, Mrgpra3+, Mrgprd+, Htr3a+, Htr1f+, IL31ra+, Osmr+, and Lpar3+ DRG neurons, were significantly decreased, which may explain that CFA treatment caused itch suppression. This study indicated that itch sensation was affected after CFA treatment, although negatively, and comprehensive but not specific suppression of different pruriceptors was observed after CFA treatment, suggesting that a unified adaptive change of increased pain and decreased itch will occur simultaneously under CFA-induced inflammatory conditions.

To identify variables associated with longitudinal change in meniscal extrusion, which might be used as possible targets for knee osteoarthritis (KOA) prevention.

In a high-risk population of middle-aged overweight women, meniscal extrusion was assessed with magnetic resonance imaging (1.5 T, coronal proton density, in-plane resolution 0.5 mm2, Sante DICOM Editor) at baseline and after 30 months. Outcomes were the absolute change in medial and lateral extrusion (mm) and relative change in extrusion (%). Based upon literature, eleven factors were hypothesized to be associated with longitudinal change. Generalized estimating equations were used to model the effect on meniscal change (p< 0.05).

677 knees of 343 women were available for analysis, with a mean age of 55.7 years (+/- 3.2) and a mean body mass index (BMI) of 32.3 kg/m2 (+/- 4.2). The greatest change in meniscal extrusion appeared medially with incident meniscal tear (4.4%; absolute 0.9 mm (95% CI 0.3, 1.5; p= 0.004); relative 14.5% (4.4, 24.7; 0.005)). Varus malalignment was associated with an increase of medial extrusion of 0.6 mm (37.6%; 0.1, 1.0; 0.009)). A 5 kg/m2 higher baseline BMI was associated with absolute and relative increase of medial extrusion of 0.2 mm and 2.96% (0.1, 0.3; <0.001 and 1.3, 4.8; 0.002). Less explicit but significant changes in extrusion appeared with longitudinal change in BMI.

Meniscal tears, varus malalignment and BMI were significantly associated with change in meniscal extrusion in middle-aged overweight women, providing viable therapeutic targets to prevent or reduce extrusion and thereby decelerate KOA development.

Meniscal tears, varus malalignment and BMI were significantly associated with change in meniscal extrusion in middle-aged overweight women, providing viable therapeutic targets to prevent or reduce extrusion and thereby decelerate KOA development.

Nonsurgical rejuvenation of the tear-trough area via the use of injectable filler material has become a popular procedure in facial rejuvenation. This procedure offers immediate, albeit temporary, results with minimal recovery time.

This systematic review aims to report on patient satisfaction and complication rates to further guide practitioners.

PubMed, Cochrane, and Scopus libraries were queried for articles using the relevant terms. Articles with greater than 5 patients who reported on satisfaction and/or complications from the procedure were included for review. Besides these variables, we noted other aspects of injection such as filler material, technique, needle or cannula delivery, among others. Studies which did not otherwise fulfill inclusion criteria for statistical analysis but reported on intravascular injection related complications were cited.

Initial query resulted in 1,655 studies which were assessed for duplicates and inclusion/exclusion criteria. After screening, 28 articles were included for analysis. 1,956 patients were captured who had been injected with one of 4 materials hyaluronic acid (1,535), CaHa (376), autologous fibroblast/keratin gel (35), and collagen-based filler (10). Short- and long-term satisfaction rates were 84.4% and 76.7%, respectively. Minor complications were common (44%). Secondarily, we found the use of cannula for filler injection of this region to be associated with a lower rate of ecchymosis (7% vs 17%, p<0.05).

Filler injection volumization of the tear-trough deformity is an effective technique for facial rejuvenation associated with high patient satisfaction. Multiple filler materials offer acceptable satisfaction and complication profiles.

Filler injection volumization of the tear-trough deformity is an effective technique for facial rejuvenation associated with high patient satisfaction. Multiple filler materials offer acceptable satisfaction and complication profiles.Large-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1-3 However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4-5 and thus does not pertain to long-term efficacy. To evaluate the duration of pro- tection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the per- formance of blinded and unblinded crossover designs in estimating long-term VE.Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Specifically, three-repeat tau and four-repeat tau in Alzheimer's disease (AD), three-repeat tau in Pick's disease (PiD) and four-repeat in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) form amyloid-like fibrous structures that accumulate in neurons and/or glial cells. Amplification and cell-to-cell transmission of abnormal tau based on the prion hypothesis are believed to explain the onset and progression of tauopathies. Recent studies support not only the self-propagation of abnormal tau, but also the presence of conformationally distinct tau aggregates, namely tau strains. Cryo-electron microscopy analyses of patient-derived tau filaments have revealed disease-specific ordered tau structures. However, it remains unclear whether the ultrastructural and biochemical properties of tau strains are inherited during the amplification of abnormal tau in the brain. In this study, we investigatnfluences the prion-like seeding activity.

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. To improve the health status and reduce symptom burden, it is important to identify a group of patients with similar characteristics and prognosis, called clinical phenotypes. Herein we shall review the different phenotypes of COPD.

Keywords (COPD, phenotype, acute exacerbation) search was conducted in PubMed, Google Scholar.

Those with raised blood eosinophil counts respond better to steroid therapy at stable state and exacerbation.

There is no universally accepted blood eosinophil cut-off value that will indicate favourable response to corticosteroids and potentially for future biologic therapy.

There is an urgent need for further therapeutic options for COPD patients with non-eosinophilic inflammation.

Well-designed COPD trials with identification of phenotypes for more personalization of the treatment of COPD.

Well-designed COPD trials with identification of phenotypes for more personalization of the treatment of COPD.

Previous studies have demonstrated an association between gait speed and cognitive function. However, the relationship between balance and cognition remains less well explored. This study examined the cross-sectional and longitudinal relationship of balance and cognitive decline in older adults.

A cohort of 4,811 adults, aged ≥65years, participating in the Cardiovascular Health Study was followed for 6years. Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST) were used to measure cognition. Tandem balance measures were used to evaluate balance. Regression models were adjusted for demographics, behavioural and disease factors.

Worse balance was independently associated with worse cognition in cross-sectional analysis. Longitudinally, participants aged ≥76years with poorer balance had a faster rate of decline after adjustment for co-variates -0.97 points faster decline in 3MSE per year (95% confidence interval (CI) -1.32, -0.63) compared to the participants with good balance. There was no association of balance and change in 3MSE among adults aged <76years (P value for balance and age interaction < 0.0001). DSST scores reflected -0.21 (95% CI -0.37, -0.05) points greater decline when adjusted for co-variates. In Cox proportional hazard models, participants with worse balance had a higher risk of being cognitively impaired over the 6 years of follow-up visits (adjusted HR1.72, 95% CI 1.30, 2.29).

Future studies should evaluate standing balance as a potential screening technique to identify individuals at risk of cognitive decline. Furthermore, a better understanding of the pathophysiological link between balance and cognition may inform strategies to prevent cognitive decline.

Future studies should evaluate standing balance as a potential screening technique to identify individuals at risk of cognitive decline. Furthermore, a better understanding of the pathophysiological link between balance and cognition may inform strategies to prevent cognitive decline.