Combination Therapy for HIV-Associated Cryptococcal Meningitis-A Success Story.

Cryptococcal meningitis is the leading cause of adult meningitis in patients with HIV, and accounts for 15% of all HIV-related deaths in sub-Saharan Africa. The mainstay of management is effective antifungal therapy, despite a limited arsenal of antifungal drugs, significant progress has been made developing effective treatment strategies by using combination regimens. The introduction of fluconazole as a safe and effective step-down therapy allowed for shorter courses of more fungicidal agents to be given as induction therapy, with higher doses achieving more rapid CSF sterilisation and improved treatment outcomes.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies.

What does Success Look Like for Leaders of Integrated Health and Social Care Systems? a Realist Review.

Introduction: Health and social care services in England are moving towards greater integration, yet little is known about how leadership of integrated care teams and systems can be supported and improved. This realist review explores what works about the leadership of integrated care teams and systems, for whom, in what circumstances and why.

Methods: A realist synthesis approach was undertaken in 2020 to explore English language literature on the leadership of integrated care teams and systems, complemented by ongoing stakeholder consultation.

Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis.

Objective: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes.

'With every fibre of their being': Perspectives of healthcare professionals caring for children with non-malignant life-limiting conditions.

Background: Children with non-malignant life-limiting conditions (NMLLCs) constitute the largest proportion of children requiring palliative care. In part, due to technological advances, growing numbers of such children are experiencing improved survival. Care is mostly provided at home by the family, with significant professional input at different points in the child's life trajectory.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial.

Background: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.

The nose is the best niche for detection of experimental pneumococcal colonisation in adults of all ages, using nasal wash.

Previous studies have suggested that the pneumococcal niche changes from the nasopharynx to the oral cavity with age. We use an Experimental Human Pneumococcal Challenge model to investigate pneumococcal colonisation in different anatomical niches with age. Healthy adults (n = 112) were intranasally inoculated with Streptococcus pneumoniae serotype 6B (Spn6B) and were categorised as young 18-55 years (n = 57) or older > 55 years (n = 55).

A retrospective study examining the adverse effect of childhood abuse among adult psychiatric service users in Britain.

The long-term effects of childhood abuse have been well studied though the effects of abuse of specific types in adult psychiatric service users are less known. This study aimed to assess the association between childhood abuse and the development of harmful social and behavioural outcomes among adult psychiatric service users. Adult psychiatric service users were accessed from secondary mental health services in South London.

Association between Patellofemoral Anatomy and Chondral Lesions of the Knee in Patellofemoral Instability.

Chondral injury is a serious consequence of patellar dislocation and patellofemoral instability (PFI). There is limited data on the relationship between radiological features such as sulcus angle and patellar height to the presence, location, and severity of chondral lesions. The purpose of this study was to determine the association of anatomical variants in patellofemoral instability with injuries sustained due to patellar dislocation.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g.

Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations.

Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide.

Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy.

Steroid use and misuse: a key performance indicator in the management of IBD.

Corticosteroids remain an important tool for inducing remission in inflammatory bowel disease (IBD) but they have no role in maintenance of remission. The significant adverse side effect profile of these drugs means their use should be avoided where possible or measures taken to reduce their risk. Despite an expanding array of alternative therapies, corticosteroid dependency and excess remain common.

Changes in pain catastrophization and neuropathic pain following operative stabilisation for patellofemoral instability: a prospective study with twelve month follow-up.

Purpose: To determine the prevalence and change in neuropathic pain or pain catastrophizing before and 12 months following patellar stabilisation surgery for patellofemoral instability.

Methods: We conducted a prospective clinical audit within a UK NHS orthopaedic surgical centre. Data from 84 patients with patellofemoral instability requiring stabilisation were analysed.

Interventions to promote family member involvement in adult critical care settings: a systematic review.

Objective: To identify, appraise and synthesise evidence of interventions designed to promote family member involvement in adult critical care units; and to develop a working typology of interventions for use by health professionals and family members.

Design: Mixed-method systematic review.

Data Sources: Bibliographic databases were searched without date restriction up to June 2019: MEDLINE, EMBASE and CINAHL; the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries.

What are the risk factors and presenting features of premature physeal arrest of the distal radius? A systematic review.

Introduction: Premature physeal arrest (PPA) of the distal radius is considered a rare complication of physeal wrist fractures. Standardised guidelines for duration of follow up do not exist. The aim of this review is to recognise the risk factors of PPA and guide follow up protocols.

Antibiotic prescription monitoring and feedback in primary care in Switzerland: Design and rationale of a nationwide pragmatic randomized controlled trial.

Introduction: Antibiotic consumption is highest in primary care, and antibiotic overuse furthers antimicrobial resistance. In our recently published pilot-RCT, we used monthly aggregated claims data to provide personalized antibiotic prescription feedback to general practitioners (GPs). The pilot-RCT has shown that personalized prescription feedback is a feasible and promising low-cost intervention to reduce antibiotic prescribing.

'Starting Out in Haziness': Parental Experiences Surrounding the Diagnosis of their Child's Non-Malignant Life-Limiting Condition in Ireland.

Purpose: To explore parental experiences surrounding the diagnosis of their child's non-malignant life-limiting condition.

Design And Methods: A qualitative descriptive study design using single-occasion one-to-one semi-structured interviews collected data from twenty-three parents of children diagnosed with non-malignant life-limiting conditions.

Findings: 'Starting out in haziness' was the central concept when parents' recounted the time they learnt of their child's diagnosis.

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

Introduction: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic.

Methods And Analysis: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019.

Timing of carotid endarterectomy and clinical outcomes.

The timing of carotid endarterectomy (CEA) for symptomatic ipsilateral carotid artery stenosis has evolved in practice over time. Key landmark trials outlined the benefit of performing CEA in the recently symptomatic carotid artery stenosis, defined as revascularisation within 6 months of the index neurological event. Further evidence and sub-analysis demonstrate that performing CEA within 2 weeks of symptoms has the maximal benefit in reducing stroke free survival and is associated with a safe perioperative complication profile.

Dopamine and reward hypersensitivity in Parkinson's disease with impulse control disorder.

Impulse control disorders in Parkinson's disease are common neuropsychiatric complications associated with dopamine replacement therapy. Some patients treated with dopamine agonists develop pathological behaviours, such as gambling, compulsive eating, shopping, or disinhibited sexual behaviours, which can have a severe impact on their lives and that of their families. In this study we investigated whether hypersensitivity to reward might contribute to these pathological behaviours and how this is influenced by dopaminergic medication.

Safety, Tolerability, and Dose Proportionality of a Novel Transdermal Fentanyl Matrix Patch and Bioequivalence With a Matrix Fentanyl Patch: Two Phase 1 Single-Center Open-Label, Randomized Crossover Studies in Healthy Japanese Volunteers.

Two open-label, single-dose, randomized crossover studies were conducted in healthy Japanesemen to (1) assess dose proportionality of 5 doses (1.38, 2.75, 5.