Indoor environmental quality (IEQ) has become an important component of green building certification schemes. While green buildings are expected to provide enhanced IEQ, higher occupant satisfaction, ...and less risks of occupant health when compared with non‐green buildings, the literature suggests inconsistent evidence due to diverse research design, small sample size, and weak statistical analysis. This study compared several outcomes pertinent to IEQ performance in green and non‐green office buildings in Singapore. Adopting a cross‐sectional study design, objective measurements were taken in eight green and six non‐green buildings, and satisfaction and acute health symptom risks of 367 occupants were obtained. Green buildings exhibited lower concentration of PM2.5, bacteria, and fungi and maintained temperature and humidity more consistently compared to non‐green counterparts. The mean ratings for satisfaction with temperature, humidity, lighting level, air quality, and indoor environment were higher in green buildings (with statistical significance P < 0.05). There was statistically significant reduction in risk of occupants having headache, unusual fatigue, and irritated skin in green buildings. Although matching of buildings and occupant characteristics, survey participation bias, and sampling duration (a 1‐week snapshot) of IEQ monitoring remain as limitations, this study offered positive association of green buildings with qualitatively and quantitatively measured performance of IEQ.
To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.
Systematic review and meta-analysis.
PubMed, Embase, Central Register of Controlled Trials, COVID-19 ...Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.
Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.
A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.
82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I
=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I
=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I
=89%; 0.29, 0.11 to 0.58, I
=97%), and solid cancers (0.55, 0.46 to 0.65, I
=78%; 0.44, 0.36 to 0.53, I
=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I
=0%; 0.06, 0.04 to 0.08, I
=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I
=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I
=88%; 0.62, 0.54 to 0.70, I
=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I
=92%; 0.77, 0.66 to 0.85, I
=93%), and solid cancers (0.90, 0.88 to 0.93, I
=51%; 0.89, 0.86 to 0.91, I
=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I
=0%; 0.97, 0.83 to 1.00, I
=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.
Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.
PROSPERO CRD42021272088.
Background
Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ...ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28–8 and Ventana SP-142 assays in GC PD-L1 IHC.
Methods
In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer.
Results
The percentage of PD-L1-positive samples at clinically relevant CPS ≥ 1, ≥ 5 and ≥ 10 cut-offs for the 28–8 assay were approximately two-fold higher than that of the 22C3 (CPS ≥ 1: 70.3 vs 49.4%,
p
< 0.001; CPS ≥ 5: 29.1 vs 13.4%,
p
< 0.001; CPS ≥ 10: 13.7 vs 7.0%,
p
= 0.004). The mean CPS score on 28–8 assay was nearly double that of the 22C3 (6.39 ± 14.5 vs 3.46 ± 8.98,
p
< 0.001). At the clinically important CPS ≥ 5 cut-off, there was only moderate concordance between the 22C3 and 28–8 assays.
Conclusion
Our findings suggest that scoring PD-L1 CPS with the 28–8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.
Summary Background & aims The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims ...to determine the prevalence of malnutrition in a tertiary hospital in Singapore and its impact on hospitalization outcomes and costs, controlling for DRG. Methods This prospective cohort study included a matched case control study. Subjective Global Assessment was used to assess the nutritional status on admission of 818 adults. Hospitalization outcomes over 3 years were adjusted for gender, age, ethnicity, and matched for DRG. Results Malnourished patients (29%) had longer hospital stays (6.9 ± 7.3 days vs. 4.6 ± 5.6 days, p < 0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95% CI 1.1–3.2, p = 0.025). Within a DRG, the mean difference between actual cost of hospitalization and the average cost for malnourished patients was greater than well-nourished patients ( p = 0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p < 0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95% CI 3.3–6.0, p < 0.001). Conclusions Malnutrition was evident in up to one third of the inpatients and led to poor hospitalization outcomes and survival as well as increased costs of care, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.
Purpose
Social isolation in older adults is a major public health problem and associated with increased morbidity and mortality. There are limited data on the association between social isolation and ...physical function including gait speed. Hence, this study is to determine the prevalence of social isolation and its association with gait speed, frailty, cognition, depression and comorbidities amongst community-dwelling older adults.
Methods
Social isolation, depression, frailty and perceived general health were assessed using 6-item Lubben Social Network Scale (LSNS-6), Geriatric Depression Scale (GDS), FRAIL scale and EuroQol EQ-5D-5L questionnaire which includes EQ Visual Analogue Scale (EQ-VAS), respectively. Cognition was assessed using the Chinese Mini Mental State Examination (cMMSE), while physical performance test included gait speed and short physical performance battery test. Binary logistic regression was performed to determine the influence of socio-demographic, medical, functional and cognitive variables on social isolation.
Results
Out of 202 participants, 27.7% were robust, 66.8% of participants were pre-frail, and 5.4% of participants were frail. Almost half (45.5%,
n
= 92) of the participants were found to be at risk of social isolation. A poor social network was negatively associated with mean gait speed (OR = 0.674, CI 0.464–0.979,
p
= 0.039), EQ-VAS (OR = 0.561, CI 0.390–0.806,
p
< 0.01) and cMMSE (OR = 0.630, 95% CI 0.413–0.960,
p
= 0.032).
Conclusion
Almost half of older adults in the community are at risk of social isolation with a very significant association with gait speed, cMMSE and EQ-VAS scores.
Abstract Objective The psychological and coping responses of the noninfected community towards infectious disease outbreaks are relatively understudied. This cross-sectional study sought to determine ...the prevalence of severe acute respiratory syndrome (SARS)-related psychiatric and posttraumatic morbidities and associated coping styles within the general population visiting community health care services. Methods It was conducted on individuals attending community polyclinics in Singapore within the first week of July 2003, 16 weeks after the first national outbreak of SARS. The General Health Questionnaire-28, Impact of Event Scale-Revised, and Brief COPE were used to determine the prevalence rates of psychiatric and posttraumatic morbidities and employed coping strategies respectively. Results The overall response rate was 78.0%. Of the 415 community health care setting respondents, we found significant rates of SARS-related psychiatric (22.9%) and posttraumatic morbidities (25.8%). The presence of psychiatric morbidity was associated with the presence of high level of posttraumatic symptoms adjusted odds ratio (OR) 2.26, 95% confidence interval (CI) 1.24–4.13, P =.008. Psychiatric morbidity was further associated with being seen at fever stations (adjusted OR 1.90, 95% CI 1.08–3.34, P =.026), younger age (adjusted OR 0.97, 95% CI 0.94–0.98, P =.021), increased self blame (adjusted OR 1.67, 95% CI 1.22–2.28, P =.001), less substance use (adjusted OR 0.74, 95% CI 0.56–0.98, P =.034) and posttraumatic morbidity was associated with increased use of denial (adjusted OR 1.31, 95% CI 1.04–1.67, P =.024), and planning (adjusted OR 1.51, 95% CI 1.16–1.95, P =.002) as coping measures. Conclusion These findings could potentially inform the development of practical community mental health programs for future infectious disease outbreaks.
AbstractObjectiveTo clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery ...of smell and taste.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.Review methodsTwo blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included.Data extraction and synthesisTwo reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery.Main outcome measuresThe primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste.Results18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I2=0.0-77.2%, τ2=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I2=0.0-72.1%, τ2=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell.ConclusionsA substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid.Systematic review registrationPROSPERO CRD42021283922.
Background
Laparoscopic subtotal cholecystectomy (LSC) is a safe bailout procedure in situations when dissection of "critical view of safety" is not possible. After the proposed classification of ...subtotal cholecystectomy into "fenestrating" and "reconstituting" techniques in 2016, a comparative review of the outcomes of both methods is timely.
Methods
A literature search of the PubMed, Cochrane Library, and Web of Science database was conducted up to January 31, 2020 for studies that reported LSC. Studies reporting LSC only in patients with Mirizzi syndrome or xanthogranulomatous cholecystitis were excluded. Our analysis includes 39 studies with 1784 cases of LSC. We report a comparison of outcomes between reconstituting and fenestrating LSC on 1505 cases 935 reconstituting (62.1%) and 570 fenestrating (37.9%).
Results
Following LSC, the rate of open conversion is 7.7%, hemorrhage is 0.4%, bile duct injury is 0.3%, bile leak is 15.4%, retained stone is 4.6%, subhepatic or subphrenic collection is 2.9%, superficial surgical site infection is 2.0% and 30-day mortality is 0.2%. 8.8% of patients required postoperative endoscopic retrograde cholangiopancreatography (ERCP), 1.1% required percutaneous intervention, and 2.2% required reoperation. Compared to reconstituting LSC, fenestrating LSC has a higher incidence of open conversion (
n
= 58, 10.2% vs.
n
= 43, 4.6%,
p
< 0.001), retained stones (
n
= 38, 6.7% vs.
n
= 38, 4.1%,
p
= 0.0253), subhepatic or subphrenic collections (
n
= 33, 5.8% vs.
n
= 13, 1.4%,
p
< 0.001), superficial surgical site infections (
n
= 18, 3.2% vs.
n
= 14, 1.5%,
p
= 0.0303), postoperative ERCP (
n
= 82, 14.4% vs.
n
= 62, 6.6%,
p
< 0.001), and need for reoperation (
n
= 20, 3.5% vs.
n
= 12, 1.3%,
p
< 0.001).
Conclusions
Although reconstituting LSC has better outcomes, both techniques are complementary. Intraoperative findings and surgical expertise impact the choice.
To date, there are no predictive biomarkers to guide selection of patients with gastric cancer (GC) who benefit from paclitaxel. Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) was a ...2×2 factorial randomised phase III study in which patients with GC were randomised to Pac-S-1 (paclitaxel +S-1), Pac-UFT (paclitaxel +UFT), S-1 alone or UFT alone after curative surgery.
The primary objective of this study was to identify a gene signature that predicts survival benefit from paclitaxel chemotherapy in GC patients. SAMIT GC samples were profiled using a customised 476 gene NanoString panel. A random forest machine-learning model was applied on the NanoString profiles to develop a gene signature. An independent cohort of metastatic patients with GC treated with paclitaxel and ramucirumab (Pac-Ram) served as an external validation cohort.
From the SAMIT trial 499 samples were analysed in this study. From the Pac-S-1 training cohort, the random forest model generated a 19-gene signature assigning patients to two groups: Pac-Sensitive and Pac-Resistant. In the Pac-UFT validation cohort, Pac-Sensitive patients exhibited a significant improvement in disease free survival (DFS): 3-year DFS 66% vs 40% (HR 0.44, p=0.0029). There was no survival difference between Pac-Sensitive and Pac-Resistant in the UFT or S-1 alone arms, test of interaction p<0.001. In the external Pac-Ram validation cohort, the signature predicted benefit for Pac-Sensitive (median PFS 147 days vs 112 days, HR 0.48, p=0.022).
Using machine-learning techniques on one of the largest GC trials (SAMIT), we identify a gene signature representing the first predictive biomarker for paclitaxel benefit.
UMIN Clinical Trials Registry: C000000082 (SAMIT); ClinicalTrials.gov identifier, 02628951 (South Korean trial).
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