ObjectiveTo identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas.Data sourceMedline, Embase, Cochrane Central ...Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019.Study selectionThe inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons.Data analysisThe potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model.Results1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2–0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (<0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25).ConclusionPatients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects.
ObjectivesSARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, ...particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear.DesignSystematic review.Data sourcesWe searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020.Eligibility criteriaAll comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing.ResultsOf 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified.ConclusionsThere is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.
Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that ...mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics.
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•Drosophila Piezo regulates cell proliferation and tissue stiffening of gliomas•Human PIEZO1 is overexpressed in aggressive gliomas and predicts poor survival•Piezo/PIEZO1 interacts with integrin-FAK signaling to regulate tumor stiffness•PIEZO1 co-opts aberrant tissue mechanics to promote glioma aggression
PIEZO1 is an ion channel that converts mechanical stimuli into cellular signaling. Here, Chen et al. perform multi-species studies to define a feedforward circuit mediated by PIEZO1 and tumor tissue mechanics to promote glioma growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence ...regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products.
Source
Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv.
Review 1
: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure.
Review 2:
we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology.
Principal findings
No eligible studies included COVID-19 patients.
Review 1:
12 RCTs (
n
= 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk RR, 0.85; 95% confidence interval CI, 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively).
Review 2
: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density.
Conclusions
High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective:
Estimates of mood and anxiety disorders are highly variable among migrant groups, as they are influenced by the socio-political context. Our objective was to conduct a systematic review ...and meta-analysis to synthesize available Canadian evidence on the prevalence and incidence of mood and anxiety disorders among migrant groups.
Methods:
Studies were identified from MEDLINE, EMBASE, and PsycINFO. They were included if they used population-based samples, presented data on the incidence or prevalence of diagnosed or self-reported mood or anxiety disorders for first-generation migrant groups in Canada, and used a Canadian-born or long-term resident reference group.
Results:
Nineteen studies met our inclusion criteria. Prevalence ratios ranged from 0.48 to 0.87, and nearly all estimates were obtained from population health surveys. Prevalence estimates among migrant groups were lower than the reference group, with the 90th percentile of estimates ranging from 1.5% to 8.2%. Risk factors for mood and anxiety disorders among migrants included being female, younger, unemployed, having lower income, and living in neighborhoods with a lower proportion of migrants.
Conclusions:
There remain many gaps in our current understanding of mood and anxiety disorders among migrant groups in Canada. Although evidence suggests the prevalence of mood and anxiety disorders are consistently lower among migrant groups, a lack of incidence estimates limits the strength of this conclusion. Future research should focus on comparisons of self-reported and diagnosed estimates, the use of a range of different primary or secondary data sources, and consideration of important risk factors.
Prospero Citation:
Jordan Edwards, Malini Hu, Amardeep Thind, Saverio Stranges, Maria Chiu, Kelly Anderson. The burden of mood and anxiety disorders among immigrant and refugee populations in Canada: a systematic review. PROSPERO 2018 CRD42018087869 Available from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018087869.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. ...Here, we show that Sox2+ tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries. Sox2+ tumor cells perceive substrate stiffness to sustain local intracellular calcium, actomyosin tension, and adhesion to promote cellular process growth and cell surface sequestration of β-catenin. Piezo2 knockout reverses WNT/β-catenin signaling states between Sox2+ tumor cells and endothelial cells, compromises the BTB, reduces the quiescence of Sox2+ tumor cells, and markedly enhances the MB response to chemotherapy. Our study reveals that mechanosensitive tumor cells construct the BTB to mask tumor chemosensitivity. Targeting Piezo2 addresses the BTB and tumor quiescence properties that underlie treatment failures in brain cancer.
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•Tumor cells ensheathe capillaries to construct the BTB•BTB-constructing tumor cells respond to mechanical cues•Piezo2 governs WNT/β-catenin signaling in tumor and endothelial cells in the BTB•Piezo2 knockout disrupts BTB and tumor quiescence to elevate chemosensitivity
Blood-tumor barrier (BTB) and tumor cell quiescence are two major obstacles in brain cancer treatment. Chen, Momin, and Wanggou et al. show that mechanosensitive tumor cells construct the BTB. Targeting Piezo2 perturbs the BTB and decreases tumor cell quiescence to enhance chemosensitivity of medulloblastoma, the most common pediatric brain cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Background: Anemia is common in cancer patients and cancer-related anemia has been associated with poorer clinical outcomes in various malignancies. The degree of anemia in patients receiving ...chemotherapy, as a prognostic factor in gastroesophageal cancers (GE), is not well understood. There have been studies looking at clinical prognostic scores and their efficacy of predicting outcomes, of which the Gustave Roussy Immune (GRIm-Score) has been seen to be most predictive of early death in GE cancers. This study aims to compare hemoglobin (g/L) values before treatment and at multiple longitudinal timepoints during treatment as a prognostic marker of overall survival (OS) and progression-free survival (PFS). It also aims to identify whether various laboratory measures in the GRIm-Score, which includes lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR) and body mass index (BMI) may hold prognostic value. Methods: A retrospective analysis of 171 patients with advanced GE cancer receiving first-line palliative-intent systemic therapy at the Princess Margaret Cancer Centre in Toronto, Canada from 2011 to 2021 was performed. Laboratory data were longitudinally collected across four time points: pre-chemotherapy, at first restaging scan, at disease progression and at final blood draw at last known follow up. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between change in hemoglobin from baseline, adjusted for LDH, NLR and BMI. Results: Mean hemoglobin value decreased with chemotherapy initiation at the first staging time point compared to pre-chemotherapy values by 10.82 g/L (-10.82, CI: -13.57, -8.07, p < 0.001). On univariate analysis, patients with a hemoglobin increase of 10 g/L at their final blood draw compared to pre-chemotherapy decreased their overall risk of death by 8.50% (HR 0.915, CI: 0.843-0.993, p = 0.033) as well as their PFS by 6.90% (HR 0.931, CI: 0.873-0.994, p = 0.031). On multivariable analysis, adjusting for relevant clinical factors including LDH, NLR and BMI, an increase in hemoglobin increase of 10 g/L from baseline to final was associated with better OS (HR 0.893, CI: 0.817-0.977, p = 0.01). On multivariate analysis, an increase in LDH at progression bloodwork compared to baseline levels was associated with poorer OS (HR 1.002, CI: 1.001-1.003, p = 0.026) and an increase in NLR at final blood draw compared to baseline was associated with poorer OS (HR 1.02, CI: 1.012-1.028, p < 0.001). Conclusions: Patients with metastatic GE cancers can develop treatment-associated anemia and this prognosticates a poorer overall survival. Prognostic models incorporating change in hemoglobin, LDH and NLR ratios should be considered in future clinical evaluation of metastatic GE cancers.
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