Tag: pubmed

J Investig Med. 2021 Jun 7:jim-2021-001816. doi: 10.1136/jim-2021-001816. Online ahead of print.

ABSTRACT

The role of thrombolysis in submassive pulmonary embolism (PE) is controversial due to the high risk of hemorrhage. This study aimed to evaluate the role of half-dose tissue-type plasminogen activator (rt-PA) in preventing death/hemodynamic decompensation in submassive (intermediate-risk) PE without increasing the risk of bleeding. In a prospective, non-randomized, open-label, single-center trial, we compared 50 mg rt-PA plus low molecular weight heparin (LMWH) with LMWH in submassive (intermediate-risk) PE. Eligible cases had confirmed pulmonary hypertension on echocardiography, and/or right ventricular cavity expansion and/or interventricular septal deviation on echocardiography, and/or right to left ventricular ratio equal to or greater than 0.9 mm on CT angiography. The primary outcome was death or hemodynamic decompensation within 7 and 30 days after treatment was given. The primary safety outcome was major extracranial bleeding or hemorrhagic stroke within 7 days. Seventy-six patients were included in the study. Total death/hemodynamic decompensation in the first 7 and 30 days was significantly less in the half-dose rt-PA group than in the LMWH group (p=0.028 and p=0.009, respectively). No significant differences were found between the two groups in terms of recurrent embolism and pulmonary hypertension at 6-month follow-up (p=1.000 and p=0.778). There was no intracranial hemorrhage in any of the patients. There were no statistically significant differences between the two groups in terms of major or minor bleeding complications. This trial showed half-dose rt-PA treatment in submassive (intermediate-risk) PE prevented death/hemodynamic decompensation in the first 7-day and 30-day period compared with LMWH treatment without increasing the risk of bleeding.

PMID:34099544 | DOI:10.1136/jim-2021-001816

Cancer Discov. 2021 Jun 7:candisc.1500.2020. doi: 10.1158/2159-8290.CD-20-1500. Online ahead of print.

ABSTRACT

Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 lung cancer patients under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progress-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted NK cells and decreased CD8+ T cell and NK cell populations in patients with MET-amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3′-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.

PMID:34099454 | DOI:10.1158/2159-8290.CD-20-1500

BMJ Glob Health. 2021 Jun;6(6):e005238. doi: 10.1136/bmjgh-2021-005238.

ABSTRACT

BACKGROUND: Little is known about the contribution of community health posts and community health workers (CHWs) to geographical accessibility of primary healthcare (PHC) services at community level and strategies for optimising geographical accessibility to these services.

METHODS: Using a complete georeferenced census of community health posts and CHWs in Niger and other high-resolution spatial datasets, we modelled travel times to community health posts and CHWs between 2000 and 2013, accounting for training, commodities and maximum population capacity. We estimated additional CHWs needed to optimise geographical accessibility of the population beyond the reach of the existing community health post network. We assessed the efficiency of geographical targeting of the existing community health post network compared with networks designed to optimise geographical targeting of the estimated population, under-5 deaths and Plasmodium falciparum malaria cases.

RESULTS: The per cent of the population within 60-minute walking to the nearest community health post with a CHW increased from 0.0% to 17.5% between 2000 and 2013. An estimated 10.4 million people (58.5%) remained beyond a 60-minute catchment of community health posts. Optimal deployment of 7741 additional CHWs could increase geographical coverage from 41.5% to 82.9%. Geographical targeting of the existing community health post network was inefficient but optimised networks could improve efficiency by 32.3%-47.1%, depending on targeting metric.

INTERPRETATIONS: We provide the first estimates of geographical accessibility to community health posts and CHWs at national scale in Niger, highlighting improvements between 2000 and 2013, geographies where gaps remained and approaches for optimising geographical accessibility to PHC services at community level.

PMID:34099482 | DOI:10.1136/bmjgh-2021-005238

Neurology. 2021 Jun 7:10.1212/WNL.0000000000012343. doi: 10.1212/WNL.0000000000012343. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relationship between late-life duration of poverty exposure and cognitive function and decline among older adults in China.

METHODS: Data were from 3,209 participants aged ≥64 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Duration of poverty, defined according to urban and rural regional standards from the China Statistical Yearbook, was assessed based on annual household income from 2005-2011 (never in poverty; 1/3 of the period in poverty; ≥2/3 of the period in poverty). Cognitive function was measured by the Chinese Mini Mental State Exam (CMMSE) from 2011-2018. We used attrition-weighted, multivariable mixed-effects Tobit regression to examine the association of duration of poverty with cognitive function and rate of decline.

RESULTS: A total of 1,162 individuals (36.21%) were never in poverty over the period from 2005-2011, 1,172 (36.52%) were in poverty 1/3 of the period, and 875 (27.27%) were in poverty ≥2/3 of the period. A longer poverty duration was associated with lower subsequent CMMSE scores with a dose-response relationship (1/3 vs. never in poverty: β = -0.98; 95% CI: -1.61 to -0.35; ≥2/3 vs. never in poverty: β = -1.55; 95% CI: -2.29 to -0.81). However, a longer duration of poverty was associated with a slower rate of CMMSE score decline over time from 2011-2018.

CONCLUSION: These findings provide valuable evidence on the role of cumulative late-life poverty in relation to cognitive health among older adults in a rapidly urbanizing and aging middle-income country. Our findings may support a compensation hypothesis for cognitive reserve in this setting.

PMID:34099525 | DOI:10.1212/WNL.0000000000012343

J Am Soc Cytopathol. 2021 May 19:S2213-2945(21)00050-8. doi: 10.1016/j.jasc.2021.05.003. Online ahead of print.

ABSTRACT

INTRODUCTION: Cytopathology fellowships need measures to assess performance of fellows. We sought to compare several internal quantitative assessment metrics in our fellowship with external metrics, such as performance on the American Society of Cytopathology (ASC) Progressive Evaluation of Competency (PEC) examination and United States Medical Licensing Examination (USMLE).

METHODS: Quantitative parameters generated from our laboratory information system (LIS) on cytopathology fellows were evaluated over 6 years, including case volume and diagnostic discrepancies, in addition to ASC PEC and USMLE scores. For discrepancy reports, interpretations made by the fellow were compared with that of the cytopathologist, and classified as none (concordant), minor (<2-levels) or major (≥2-levels).

RESULTS: We evaluated internal and external metrics on 13 fellows over 6 years. The program average diagnostic concordance rate was 89.9%, with an average major discrepancy rate of 1.5%, and an average monthly case volume of 260 cases. More fellows with above-average ASC PEC performance showed above-average concordant diagnoses and lower case volume, while below-average PEC scores were seen more often with higher major discrepancy rates. More fellows with above-average USMLE scores had higher case volumes, while low USMLE scores showed a trend towards higher major discrepancy rates.

CONCLUSION: Our fellowship program has used a variety of internal and external measures of performance for cytopathology fellows. Although the findings show no statistically significant finding correlating performance, these quantitative parameters generated from our LIS were helpful to identify areas of improvement, facilitate comparison to peers, and provide case volume documentation.

PMID:34099427 | DOI:10.1016/j.jasc.2021.05.003

Women Birth. 2021 Jun 4:S1871-5192(21)00086-X. doi: 10.1016/j.wombi.2021.05.007. Online ahead of print.

ABSTRACT

PROBLEM: Although perinatal universal depression and psychosocial assessment is recommended in Australia, its clinical performance and cost-effectiveness remain uncertain.

AIM: To compare the performance and cost-effectiveness of two models of psychosocial assessment: Usual-Care and Perinatal Integrated Psychosocial Assessment (PIPA).

METHODS: Women attending their first antenatal visit were prospectively recruited to this cohort study. Endorsement of significant depressive symptoms or psychosocial risk generated an ‘at-risk’ flag identifying those needing referral to the Triage Committee. Based on its detailed algorithm, a higher threshold of risk was required to trigger the ‘at-risk’ flag for PIPA than for Usual-Care. Each model’s performance was evaluated using the midwife’s agreement with the ‘at-risk’ flag as the reference standard. Cost-effectiveness was limited to the identification of True Positive and False Positive cases. Staffing costs associated with administering each screening model were quantified using a bottom-up time-in-motion approach.

FINDINGS: Both models performed well at identifying ‘at-risk’ women (sensitivity: Usual-Care 0.82 versus PIPA 0.78). However, the PIPA model was more effective at eliminating False Positives and correctly identifying ‘at-risk’ women (Positive Predictive Value: PIPA 0.69 versus Usual Care 0.41). PIPA was associated with small incremental savings for both True Positives detected and False Positives averted.

DISCUSSION: Overall PIPA performed better than Usual-Care as a psychosocial screening model and was a cost-saving and relatively effective approach for detecting True Positives and averting False Positives. These initial findings warrant evaluation of longer-term costs and outcomes of women identified by the models as ‘at-risk’ and ‘not at-risk’ of perinatal psychosocial morbidity.

PMID:34099393 | DOI:10.1016/j.wombi.2021.05.007

J Pediatr Urol. 2021 May 17:S1477-5131(21)00282-5. doi: 10.1016/j.jpurol.2021.05.014. Online ahead of print.

ABSTRACT

BACKGROUND: Despite many technical advances the debate continues on single versus staged procedures for proximal hypospadias. In this systematic review and meta-analysis we have compared the contemporary outcomes of proximal hypospadias repair: single stage foreskin pedicle tube (FPT) versus two stage foreskin free graft (FFG) and two-stage foreskin pedicled flap (FPF) over the last decade.

METHODS: A systematic literature review of publications in English of the following electronic databases was conducted: Cochrane Database, PUBMED, MEDLINE and EMBASE. The following keywords were used: (proximal) AND (hypospadias) AND (repair OR urethroplasty) AND (outcomes OR complications). The publication date range for studies was from January 2010 to December 2020. Outcomes analyzed were complications like urethro-cutaneous fistula (UCF), glans dehiscence (GD), meatal stenosis (MS), urethral stricture (US), urethral diverticulum (UD), recurrent curvature or residual chordee (RC), buried penis (BP) and poor cosmesis (PC) as per objective assessment scores, or poor graft uptake (PGF) during first stage. We also divided the papers based on case load into two groups: < 5 cases or >5 cases operated per year and compared the post-operative outcomes.

RESULTS: The I 2 statistics for prevalence of total complications showed high heterogeneity with I 2 of 88% for one stage repair and 92% & 98% for two stage repairs. The pooled data from 26 articles covered a total of 2664 patients; mean follow-up of 4.5 years (1.8-14 years). One stage repair (FPT) was used in 680 (25%) patients while two stage repair was used in 1984 (75%) patients. Complications were encountered in 285/680 (42%) of those who underwent single stage repair (FPT) and this was significantly higher (Fishers; p = 0.001) than 414/1984 (21%) complication rate seen in two stage repair. Among the two different techniques of two stage operations over-all complication rate was not significantly different (Fisher’s; p = 0.1) between FFG (155/674; 23%) and FPF (259/1310; 20%). FFG was superior to FPF in terms of individual complications UCF, MS, GD and UD. For two-stage FPT and FPF repairs the complication rate significantly reduced (p = 0.01) with increasing case load. For single stage repairs the complication rate remained high despite the increasing case load.

CONCLUSIONS: Two-stage repair of proximal hypospadias had significantly less complications compared to single stage repair. Among two-stage repairs specific complications were significantly less for FFG, although total complications were not significantly different from that seen with FPF. The results of two-stage repairs improved with higher case load supporting the concept of dedicated hypospadias centres.

PMID:34099397 | DOI:10.1016/j.jpurol.2021.05.014

Cardiovasc Revasc Med. 2021 May 19:S1553-8389(21)00257-8. doi: 10.1016/j.carrev.2021.05.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Trials investigating aspirin omission in patients taking oral anticoagulation (OAC) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) were not powered to assess rates of major bleeding or ischemic events.

METHODS: We performed an updated meta-analysis and network analysis of randomized trials comparing treatment with or without aspirin in patients taking OAC and a P2Y12-inhibitor after PCI or ACS. The primary outcome was TIMI major bleeding.

RESULTS: Five trials enrolling 11,542 patients allocated to antithrombotic regimens omitting (n = 5795) or including aspirin (n = 5747) were included. Aspirin omission was associated with a lower risk of TIMI major bleeding (RR = 0.56, 95% CI [0.44-0.71]; P < 0.001) but a trend towards a higher risk of MI (RR = 1.21, 95% CI [0.99-1.47]; P = 0.06), which was significantly higher when only non-vitamin K antagonist OAC (NOAC)-based trials were considered (P_interaction = 0.02). The risk of stent thrombosis was comparable with both strategies (RR = 1.29, 95% CI [0.87-1.90]; P = 0.20), with a trend towards a higher risk of ST with aspirin omission when only NOAC-based trials were considered (P_interaction = 0.06). Risks of stroke and death were similar with both strategies. Network meta-analysis ranked dabigatran (low dose) without aspirin as the best strategy for bleeding reduction (P-score = 0.86) and apixaban with aspirin as the best strategy for MI reduction (P-score = 0.66).

CONCLUSIONS: In patients taking OAC after PCI or ACS, aspirin omission is associated with a lower risk of TIMI major bleeding, with a numerically increased risk of MI, which is statistically significant when only NOAC-based trials are considered. This supports individualization of the treatment regimen based on patient risk.

PMID:34099410 | DOI:10.1016/j.carrev.2021.05.013

Chin J Traumatol. 2021 May 18:S1008-1275(21)00087-0. doi: 10.1016/j.cjtee.2021.05.003. Online ahead of print.

ABSTRACT

PURPOSE: Posttraumatic stress disorder (PTSD) is a significant global mental health concern, especially in the military. This study aimed to estimate the efficacy of mindfulness meditation in the treatment of military-related PTSD, by synthesizing evidences from randomized controlled trials.

METHODS: Five electronic databases (Pubmed, EBSCO Medline, Embase, PsychINFO and Cochrane Library) were searched for randomized controlled trials focusing on the treatment effect of mindfulness meditation on military-related PTSD. The selection of eligible studies was based on identical inclusion and exclusion criteria. Information about study characteristics, participant characteristics, intervention details, PTSD outcomes, as well as potential adverse effects was extracted from the included studies. Risk of bias of all the included studies was critically assessed using the Cochrane Collaboration’s tool. R Statistical software was performed for data analysis.

RESULTS: A total of 1902 records were initially identified and screened. After duplicates removal, 834 records were screened for title and abstract. Then, full-text of 115 related articles were retrieved and assessed for eligibility. Among them, 96 articles were excluded for no random assignment, article type of commentary, editorial, review, case report, etc. Finally, 19 articles in English language with 1326 participants were included through strict inclusion and exclusion criteria. The results revealed that mindfulness meditation had a significantly larger effect on alleviating military-related PTSD symptoms compared with control conditions, such as treatment as usual, present-centered group therapy and PTSD health education (standardized mean difference (SMD) = -0.33; 95% CI [-0.45, -0.21]; p < 0.0001). Mindfulness interventions with different control conditions (active or non-active control, SMD = -0.33, 95% CI [-0.46, -0.19]; SMD = -0.49, 95% CI [-0.88, -0.10], respectively), formats of delivery (group-based or individual-based, SMD = -0.30, 95% CI [-0.42, -0.17], SMD = -0.49, 95% CI [-0.90, -0.08], respectively) and intervention durations (short-term or standard duration, SMD = -0.27, 95% CI [-0.46, -0.08], SMD = -0.40, 95% CI [-0.58, -0.21], respectively) were equally effective in improving military-related PTSD symptoms.

CONCLUSION: Findings from this meta-analysis consolidate the efficacy and feasibility of mindfulness meditation in the treatment of military-related PTSD. Further evidences with higher quality and more rigorous design are needed in the future.

PMID:34099359 | DOI:10.1016/j.cjtee.2021.05.003

Eur J Surg Oncol. 2021 Jun 1:S0748-7983(21)00535-7. doi: 10.1016/j.ejso.2021.05.040. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients’ morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites.

MATERIALS AND METHODS: A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population.

RESULTS: Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure.

CONCLUSION: The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.

PMID:34099356 | DOI:10.1016/j.ejso.2021.05.040