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To identify factors that likely contribute to potentially inappropriate prescriptions (PIPs) among older adults in primary care settings, as well as barriers to medicines optimisation and recommended potential solutions.

Systematic review.

Quantitative studies that analysed the factors associated with PIPs among older adults (≥65 years) in primary care settings, and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population.

PubMed, EMBASE, Scopus, CINAHL, PsycINFO, Web of Science, CNKI and Wanfang.

Of the 13 167 studies identified, 50 were included (14 qualitative, 34 cross-sectional and 2 cohort). Nearly all quantitative studies examined patient-related non-clinical factors (eg, age) and clinical factors (eg, number of medications) and nine studies examined prescriber-related factors (eg, physician age). A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies, and a higher number other factors are related. Barriers to medicines optimisation among primary care older adults comprise multiple factors, and evidence-based and targeted interventions are needed to address these difficulties.

CRD42020216258.

CRD42020216258.Immunotherapies aimed at alleviating the inhibitory constraints on Tcells have revolutionised cancer management. To date, these have focused on the blockade of cell surface checkpoints such as PD-1. Herein we identify protein-tyrosine-phosphatase-1B (PTP1B) as an intracellular checkpoint that is upregulated in T cells in tumors. We show that the increased PTP1B limits T cell expansion and cytotoxicity to contribute to tumor growth. T cell-specific PTP1B deletion increased STAT-5 signaling and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumor growth. The pharmacological inhibition of PTP1B recapitulated the T cell-mediated repression of tumor growth and enhanced the response to PD-1 blockade. GW2580 clinical trial Furthermore, the deletion or inhibition of PTP1B enhanced the efficacy of adoptively-transferred chimeric-antigen-receptor (CAR) T cells against solid tumors. Our findings identify PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells and CAR T cells to combat cancer.The factors determining disease course and survival in fibrotic hypersensitivity pneumonitis (fHP) have not been fully elucidated.The aim of this study was to describe the characteristics of patients with fHP in a real-world cohort and investigate factors associated with worse outcomes. We aimed to explore the use of neutrophil to lymphocyte ratio (NLR) and peripheral blood monocyte levels in predicting mortality.

A retrospective, multicentre, observational UK cohort study.

Patients with fHP were significantly younger than those with idiopathic pulmonary fibrosis (IPF) (median age fHP 73 vs IPF 75 years) and were much more likely to be woman (fHP 61% vs IPF 26%). In almost half of all fHP cases (49%, n=104/211), no causative antigen was identified from either the history or specific antigen testing. Overall, fHP was associated with a better survival than IPF, although median survival of both groups was poor (fHP 62 months vs IPF 52 months).IPF survival in patients with a high NLR was significantly lower than those with a low NLR (44 vs 83 months). A monocyte count ≥0.95 K/uL also predicted significantly poorer outcomes for patients with IPF compared with <0.95 K/uL (33 vs 57 months). In contrast, NLR and monocyte count did not predict survival in the fHP cohort.

Although fHP has a statistically lower mortality than IPF, absolute survival time of both conditions is poor. High baseline NLR and absolute monocyte counts predict worse survival in IPF but not in fHP, highlighting the potential for divergence in their pathogenic mechanisms.

Although fHP has a statistically lower mortality than IPF, absolute survival time of both conditions is poor. High baseline NLR and absolute monocyte counts predict worse survival in IPF but not in fHP, highlighting the potential for divergence in their pathogenic mechanisms.

With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria.

We conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13.

There were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66th and social measures is needed to mitigate the resurgence of another wave.

Despite the low prevalence of HIV and broad provision of antiretroviral therapy, the Middle East and North Africa (MENA) remains the only region where new HIV infections and AIDS-related deaths are not declining. There is a dearth of evidence from MENA on antiretroviral therapy engagement. In this qualitative study, we sought to identify the ways in which successful treatment is hindered in Iran, which is home to 24% of HIV infections in MENA.

From August 2018 to January 2019, we used purposive sampling and conducted 12 individual interviews and 8 focus group discussions with 27 female and 31 male patients, in addition to 5 individual interviews with HIV care providers and 1 focus group discussion with 8 care providers. Social constructivism augmented with realist-informed thematic analysis was used to understand how the socioecological context triggers cognitive and affective mechanisms that disrupt antiretroviral therapy.

The use of Thematic Network Analysis resulted in the identification of three key first study within MENA to identify pathways through which successful treatment is hindered. It appears that lack of societal awareness regarding HIV is specific to low prevalence settings, such as MENA countries, where negative perceptions, stigma, discrimination and misinformation regarding HIV and its treatment produce denial, fear and despair, acting as mechanisms that disrupt antiretroviral therapy. The experience of despair, in response to changing economic conditions and social support, further impacts treatment experience.

Sleep disordered breathing represents a spectrum of upper airway obstruction including snoring, increased respiratory effort and obstructive sleep apnoea. An increasing demand for paediatric preoperative sleep studies and postoperative high dependency unit (HDU) beds was having a significant impact on service delivery at this ear, nose and throat (ENT) unit.

Retrospective and prospective review of all paediatric sleep study requests over a 30-month period in a single tertiary ENT department. Data were collected on indication for and result of sleep study, patient outcome, operative details and HDU bed occupancy. During the study period, a 'Sleep Study' proforma was introduced which incorporated the 'I'm Sleepy Score' (ISS) and ENT-UK national guidelines.

Retrospective review included 198 sleep studies, of which 62% (n=118) showed no evidence of obstructive sleep apnoea (OSA). There was little consistency in patients' sleep study results and need for monitoring on HDU following adenotonsillectomy. Prospeith corresponding cost benefits.

To assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use.

Retrospective cohort study.

Large administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies.

Individuals age 11-65 years and without a history of substance use (except alcohol) at baseline.

Episodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episodd naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion.

Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis.

Good collateral status was present in 67 patientrs of good collateral flow.

After aneurysmal SAH, transcranial Doppler is commonly used to monitor cerebral vasospasm. The diagnostic accuracy of transcranial Doppler flow velocity values in detecting angiographic vasospasm in patients requiring urgent endovascular intervention has not been established.

We performed a retrospective analysis of a consecutive series of patients with aneurysmal SAH who underwent transcranial Doppler (index test) within 24 hours of conventional angiography (reference test). The judgment of 33%, 50%, and 66% degree of vessel narrowing on angiography was independently established by multiple neuroendovascular clinicians. Vessel-specific per-segment and per-patient transcranial Doppler velocities were studied using receiver operating characteristic curves, the Youden index, and minimal acceptable sensitivity models. Optimal mean flow-velocity thresholds were explored to calculate sensitivity and specificity using a per-patient judgment of vasospasm of at least 50% angiographic narrowing in any large arterilusive.

Intracranial stents for the treatment of aneurysms can be responsible for parent artery straightening, a phenomenon with potential consequences for aneurysmal occlusion. We aimed to evaluate parent artery straightening following flow-diverter stent placement in patients with intracranial aneurysms and explored the association between parent artery straightening and subsequent aneurysm occlusion.

All patients treated with flow-diverter stents for anterior circulation aneurysms located downstream from the carotid siphon between January 2009 and January 2018 were screened for inclusion. Parent artery straightening was defined as the difference (α-β) in the parent artery angle at the neck level before (α angle) and after flow-diverter stent deployment (β angle). We analyzed the procedural and imaging factors associated with parent artery straightening and the associations between parent artery straightening and aneurysmal occlusion.

Ninety-five patients met the inclusion criteria (

 = 64/95 women, 67.4%; mean age, 54.