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This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to COVID-19 with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplemental materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.
Electroconvulsive therapy (ECT) remains irreplaceable in the treatment of several psychiatric conditions. However, evidence derived using data from a national database to support its safety is limited. The aim of this study was to investigate in-hospital mortality among patients with psychiatric conditions treated with and without ECT.
Using data from the Taiwan National Health Insurance Research Database from 1997 to 2013, we identified 828,899 inpatients with psychiatric conditions, among whom 0.19% (n = 1571) were treated with ECT.
We found that ECT recipients were more frequently women, were younger and physically healthier, lived in more urbanized areas, were treated in medical centers, and had longer hospital stays. ECT recipients had lower odds of in-hospital mortality than did those who did not receive ECT. Moreover, no factor was identified as being able to predict mortality in patients who underwent ECT. Among all patients, ECT was not associated with in-hospital mortality after controlling for potential confounders.
ECT was indicated to be safe and did not increase the odds of in-hospital mortality. However, ECT appeared to be administered only on physically healthy but psychiatrically compromised patients, a pattern that is in opposition with the scientific evidence supporting its safety. Moreover, our data suggest that ECT is still used as a treatment of last resort in the era of modern psychiatry.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.
Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.
Economically depressed small-town population.
Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).
Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).
Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.
We investigated the clinical predictors of methicillin-resistance and their impact on mortality in 371 patients with Staphylococcus aureus bacteraemia identified from two prospective multi-centre studies. Methicillin resistant S. aureus (MRSA) accounted for 42.2% of community-onset and 74.5% of hospital-onset cases. No significant clinical difference was found between patients infected with MRSA vs. methicillin-sensitive S. aureus (MSSA), except that the former were more likely to have had hospital-onset bacteraemia and received antibiotics in the preceding 90 days. After stratifying according to the acquisition site, prior antibiotic use was the only independent predictor of having MRSA in both community-onset and hospital-onset cases. The frequency of inappropriate empirical antibiotic therapy was higher in patients with MRSA than in those with MSSA bacteraemia. However, methicillin resistance was not a predictor of mortality in patients and the clinical characteristics and outcomes of both MRSA and MSSA bacteraemia were similar. This study indicates that there are no definitive clinical or epidemiological risk factors which could distinguish MRSA from MSSA cases with the exception of the previous use of antibiotics for having MRSA bacteraemia, which emphasises the prudent use of glycopeptide treatment of patients at risk for invasive MRSA infections.
Evidence suggests that semantic interference may be a sensitive indicator of early dementia. We examined the utility of the Semantic Interference Test (SIT), a cognitive stress memory paradigm which taps proactive and retroactive semantic interference, for predicting progression from mild cognitive impairment (MCI) to dementia in both a clinical and a population-based sample.
Participants with MCI in the clinical (n = 184) and population-based (n = 435) samples were followed for up to four years. We employed receiver operating characteristic (ROC) methods to establish optimal thresholds for four different SIT indices. Threshold performance was compared in the two samples using logistic and Cox proportional hazard regression models.
Within four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%) individuals in the population-based sample progressed to dementia. Overall classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different subtests of the SIT had slightly different performance characteristics in the two samples. However, regression models showed that thresholds established in the clinical sample performed similarly in the population sample before and after adjusting for demographics and other baseline neuropsychological test scores.
Despite differences in demographic composition and progression rates, baseline SIT scores predicted progression from MCI to dementia similarly in both samples. Thresholds that best predicted progression were slightly below thresholds established for distinguishing between amnestic MCI and cognitively normal subjects in clinical practice. This confirms the utility of the SIT in both clinical and population-based samples and establishes thresholds most predictive of progression of individuals with MCI.
Depression is one of the most common mental disorders and identifying effective treatment strategies is crucial for the control of depression. Well-conducted systematic reviews (SRs) and meta-analyses can provide the best evidence for supporting treatment decision-making. Nevertheless, the trustworthiness of conclusions can be limited by lack of methodological rigour. This study aims to assess the methodological quality of a representative sample of SRs on depression treatments.
A cross-sectional study on the bibliographical and methodological characteristics of SRs published on depression treatments trials was conducted. Two electronic databases (the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects) were searched for potential SRs. SRs with at least one meta-analysis on the effects of depression treatments were considered eligible. The methodological quality of included SRs was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. The associations between bibliographical characteristics and scoring on AMSTAR items were analysed using logistic regression analysis.
A total of 358 SRs were included and appraised. Over half of included SRs (n = 195) focused on non-pharmacological treatments and harms were reported in 45.5% (n = 163) of all studies. Studies varied in methods and reporting practices: only 112 (31.3%) took the risk of bias among primary studies into account when formulating conclusions; 245 (68.4%) did not fully declare conflict of interests; 93 (26.0%) reported an ‘a priori’ design and 104 (29.1%) provided lists of both included and excluded studies. Results from regression analyses showed: more recent publications were more likely to report ‘a priori’ designs [adjusted odds ratio (AOR) 1.31, 95% confidence interval (CI) 1.09–1.57], to describe study characteristics fully (AOR 1.16, 95% CI 1.06–1.28), and to assess presence of publication bias (AOR 1.13, 95% CI 1.06–1.19), but were less likely to list both included and excluded studies (AOR 0.86, 95% CI 0.81–0.92). SRs published in journals with higher impact factor (AOR 1.14, 95% CI 1.04–1.25), completed by more review authors (AOR 1.12, 95% CI 1.01–1.24) and SRs on non-pharmacological treatments (AOR 1.62, 95% CI 1.01–2.59) were associated with better performance in publication bias assessment.
The methodological quality of included SRs is disappointing. Future SRs should strive to improve rigour by considering of risk of bias when formulating conclusions, reporting conflict of interests and authors should explicitly describe harms. SR authors should also use appropriate methods to combine the results, prevent language and publication biases, and ensure timely updates.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.
This study aimed to evaluate the association of chronic rhinosinusitis with sudden sensorineural hearing loss using a population-based database.
Sampled subject data were obtained from the Taiwan Longitudinal Health Insurance Database 2000. A total of 3325 patients with sudden sensorineural hearing loss were identified and 9975 controls were randomly selected. A conditional logistic regression was used to calculate the odds ratio for having been previously diagnosed with chronic rhinosinusitis, for cases and controls.
Results and conclusion:
The adjusted odds ratio of having prior chronic rhinosinusitis among cases compared to controls was 1.36 (95 per cent confidence interval = 1.16–1.60). The significant relationship between sudden sensorineural hearing loss and chronic rhinosinusitis was most pronounced among those patients aged 44 years or less (compared to controls) (odds ratio = 2.18; 95 per cent confidence interval = 1.63–2.92). However, the significant relationship between sudden sensorineural hearing loss and prior chronic rhinosinusitis was not sustained for patients older than 60 years compared to controls.
A review is presented of Synchrotron X-ray Topography and KOH etching studies carried out on n type 4H-SiC offcut substrates before and after homo-epitaxial growth to study defect replication and strain relaxation processes and identify the nucleation sources of both interfacial dislocations (IDs) and half-loop arrays (HLAs) which are known to have a deleterious effect on device performance. We show that these types of defects can nucleate during epilayer growth from: (1) short segments of edge oriented basal plane dislocations (BPDs) in the substrate which are drawn by glide into the epilayer; and (2) segments of half loops of BPD that are attached to the substrate surface prior to growth which also glide into the epilayer. It is shown that the initial motion of the short edge oriented BPD segments that are drawn from the substrate into the epilayer is caused by thermal stress resulting from radial temperature gradients experienced by the wafer whilst in the epi-chamber. This same stress also causes the initial glide of the surface half-loop into the epilayer and through the advancing epilayer surface. These mobile BPD segments provide screw oriented segments that pierce the advancing epilayer surface that initially replicate as the crystal grows. Once critical thickness is reached, according to the Mathews-Blakeslee model , these screw segments glide sideways under the action of the mismatch stress leaving IDs and HLAs in their wake. The origin of the mismatch stress is shown to be associated with lattice parameter differences at the growth temperature, arising from the differences in doping concentration between substrate and epilayer.
Additional high-quality evidence for predictors of peritonsillar abscess recurrence could lead to better-informed treatment decisions regarding tonsillectomy.
In this study, 172 patients, who had been diagnosed and treated for peritonsillar abscess, were evaluated at follow up. A retrospective review of medical records and a telephone survey were performed. The clinical characteristics analysed included underlying disease, laboratory findings and computed tomography findings. Cox proportional hazard models were used to identify risk factors for peritonsillar abscess recurrence.
The recurrence rate of peritonsillar abscess was 13.9 per cent. Univariate analysis indicated that extraperitonsillar spread of the abscess (beyond the peritonsillar area) on computed tomography and a history of recurrent tonsillitis were associated with recurrence. Multivariate analysis also indicated that extraperitonsillar spread (p = 0.007; hazard ratio = 3.399) and recurrent tonsillitis history (p < 0.001; hazard ratio = 11.953) were significant risk factors for recurrence.
Our results suggest that tonsillectomy may be indicated as a treatment for peritonsillar abscess in patients with a history of recurrent tonsillitis or extraperitonsillar spread on computed tomography.
To determine whether controlling the prescription of targeted antibiotics would translate to a measurable reduction in hospital-onset Clostridium difficile infection (CDI) rates.
A multicenter before-and-after intervention comparative study.
Ten medical centers in the greater New York region. Intervention group comprised of 6 facilities with early antimicrobial stewardship programs (ASPs). The 4 facilities without ASPs made up the nonintervention group.
Intervention facilities identified target antibiotics using case-control studies and implemented ASP-based strategies to control their use. Pre- and postintervention hospital-onset CDI rates and antibiotic consumption were compared for a 20-month period from June 2010 to January 2012. Antibiotic usage was compared using defined daily dose, days of therapy, and number of courses prescribed. Comparisons used bivariate and regression techniques.
Intervention facilities identified piperacillin/tazobactam, fluoroquinolones, or cefepime (odds ratio, 2.0-9.8 in CDI case patients compared with those without CDI) as intervention targets and selected several interventions (all included a component of audit and feedback). Varying degrees of success were observed in reducing antibiotic consumption over time. Total target antibiotic use significantly decreased (P < .05) when measured by days of therapy and number of courses but not by defined daily dose. Intravenous moxifloxacin and oral ciprofloxacin use showed significant reduction when measured by defined daily dose and days of therapy (P ≤ .01). Number of courses with all forms of these antibiotics was reduced (P ≤ .005). Intervention hospitals reported fewer hospital-onset CDI cases (2.8 rate point difference) compared with nonintervention hospitals; however, we were unable to show statistically significant decreases in aggregate hospital-onset CDI either between intervention and nonintervention groups or within the intervention group over time.
Although decreases in target antibiotic consumption did not translate into reductions of hospital-onset CDI in this study, many valuable lessons (including implementation strategies and antibiotic consumption measures) were learned. The findings can inform potential policy decisions regarding incorporating control of CDI and ASP as healthcare quality measures.
Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design.
Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed.
Results suggested that EI patients had reduced suicide rate (χ2(1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR −0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery.
The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.
Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002–2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32–4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17–4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01–3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35–9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10–6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06–7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.
This paper discusses formation mechanisms and potential paths to reduce defect density in current SiC epitaxy technology. Comprehensive optimization efforts have resulted in defect density measured by laser light scattering below 0.5 cm-2 for 30 um thick epi wafers. Possible approaches to reduce basal plane dislocations and mitigate interfacial dislocations are discussed. The progress in epitaxy defect reduction has been made on the foundation of the high quality 100mm substrates. The average and median BPD density is 700 cm-2 and 500 cm-2, respectively, and a low TSD density is also achieved simultaneously with both average and median values around 350 cm-2. High quality and low stress 150mm substrates have been obtained with very low TSD density of <150 cm-2.
This multicentre surveillance study was conducted to investigate the trends in incidence and aetiology of healthcare-associated bloodstream infections (HCA-BSIs) in Taiwan. From 2000 to 2011 a total of 56 830 HCA-BSIs were recorded at three medical centres, and coagulase-negative staphylococci (CoNS) were the most common pathogens isolated (n = 9465, 16·7%), followed by E. coli (n = 7599, 13·4%). The incidence of all HCA-BSIs in each and all hospitals significantly increased over the study period owing to the increase of aerobic Gram-positive cocci and Enterobacteriaceae by 4·2% and 3·6%, respectively. Non-fermenting Gram-negative bacteria, Bacteroides spp. and Candida spp. also showed an increase but there was a significant decline in the numbers of methicillin-resistant S. aureus. In conclusion, the incidence of HCA-BSIs in Taiwan is significantly increasing, especially for Enterobacteriaceae and aerobic Gram-positive cocci.