Inference for covariate-adjusted time-dependent prognostic accuracy measures.

Evaluating the prognostic performance of candidate markers for future disease onset or progression is one of the major goals in medical research. A marker's prognostic performance refers to how well it separates patients at the high or low risk of a future disease state. Often the discriminative performance of a marker is affected by the patient characteristics (covariates). Time-dependent receiver operating characteristic (ROC) curves that ignore the informativeness of the covariates will lead to biased estimates of the accuracy parameters. We propose a time-dependent ROC curve that accounts for the informativeness of the covariates in the case of censored data. We propose inverse probability weighted (IPW) estimators for estimating the proposed accuracy parameters. We investigate the performance of the IPW estimators through simulation studies and real-life data analysis.

Understanding the role of configural processing in face emotion recognition in Parkinson's disease.

This investigation examined whether impairment in configural processing could explain deficits in face emotion recognition in people with Parkinson's disease (PD). Stimuli from the Radboud Faces Database were used to compare recognition of four negative emotion expressions by older adults with PD (n = 16) and matched controls (n = 17). Participants were tasked with categorizing emotional expressions from upright and inverted whole faces and facial composites; it is difficult to derive configural information from these two types of stimuli so featural processing should play a larger than usual role in accurate recognition of emotional expressions. We found that the PD group were impaired relative to controls in recognizing anger, disgust and fearful expressions in upright faces. Then, consistent with a configural processing deficit, participants with PD showed no composite effect when attempting to identify facial expressions of anger, disgust and fear. A face inversion effect, however, was observed in the performance of all participants in both the whole faces and facial composites tasks. These findings can be explained in terms of a configural processing deficit if it is assumed that the disruption caused by facial composites was specific to configural processing, whereas inversion reduced performance by making it difficult to derive both featural and configural information from faces.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study.

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Use of a Real-Time Locating System for Contact Tracing of Health Care Workers During the COVID-19 Pandemic at an Infectious Disease Center in Singapore: Validation Study.

BACKGROUND: In early 2020, coronavirus disease (COVID-19) emerged and spread by community and nosocomial transmission. Effective contact tracing of potentially exposed health care workers is crucial for the prevention and control of infectious disease outbreaks in the health care setting. OBJECTIVE: This study aimed to evaluate the comparative effectiveness of contact tracing during the COVID-19 pandemic through the real-time locating system (RTLS) and review of the electronic medical record (EMR) at the designated hospital for COVID-19 response in Singapore. METHODS: Over a 2-day study period, all admitted patients with COVID-19, their ward locations, and the health care workers rostered to each ward were identified to determine the total number of potential contacts between patients with COVID-19 and health care workers. The numbers of staff-patient contacts determined by EMR reviews, RTLS-based contact tracing, and a combination of both methods were evaluated. The use of EMR-based and RTLS-based contact tracing methods was further validated by comparing their sensitivity and specificity against self-reported staff-patient contacts by health care workers. RESULTS: Of 796 potential staff-patient contacts (between 17 patients and 162 staff members), 104 (13.1%) were identified by both the RTLS and EMR, 54 (6.8%) by the RTLS alone, and 99 (12.4%) by the EMR alone; 539 (67.7%) were not identified through either method. Compared to self-reported contacts, EMR reviews had a sensitivity of 47.2% and a specificity of 77.9%, while the RTLS had a sensitivity of 72.2% and a specificity of 87.7%. The highest sensitivity was obtained by including all contacts identified by either the RTLS or the EMR (sensitivity 77.8%, specificity 73.4%). CONCLUSIONS: RTLS-based contact tracing showed higher sensitivity and specificity than EMR review. Integration of both methods provided the best performance for rapid contact tracing, although technical adjustments to the RTLS and increasing user compliance with wearing of RTLS tags remain necessary.

Determinants of change in intention to receive influenza vaccination among health-care workers in Singapore.

Understanding the change in intention for influenza vaccine among health-care workers (HCWs) is important to increase influenza vaccination uptake. We aimed to investigate the psychosocial beliefs associated with a change in the intention for influenza vaccine. An anonymous cross-sectional survey was distributed to tertiary hospital HCWs in 2016. Of 3007 HCWs, 70% were compliant (vaccinated, with an intention to revaccinate), 8% were resistant (unvaccinated, without intention to vaccinate), 10% had positive change (unvaccinated, but with intention) and 12% had negative change (vaccinated, but without intention). Across HCW groups, medical staff had both the highest proportion receiving all influenza vaccinations in the last 5 years (101, 28.4%), as well as the highest proportion who had never received vaccination (41, 11.5%). With increasing age, HCWs were less likely to have a negative (p = .02) or positive change (p = .06) in intention, compared to the vaccine-resistant group. HCWs were more likely to be compliant or have a positive change in intention to receive influenza vaccine, if they perceived the vaccine as effective, safe, or had a higher frequency of influenza vaccination in the last 5 years (all with p < .05). HCWs who were medical staff, who believed that side effects of the vaccine were common, or had worked for 6 to 10 years (vs 5 years or less) were less likely to be compliant (all with p < .05). In conclusion, older HCWs were more likely to maintain the status quo in their behavior toward influenza vaccination. Influenza vaccination strategies should place emphasis on vaccine effectiveness and safety.

The Long-Term Impact of Political Activism on Mental Wellbeing in the Context of Adult Immigrants Who Experienced Childhood Political Trauma.

There is limited literature on the long-term impact of political activism on mental wellbeing in the context of childhood political trauma and subsequent forced migration. Such information is important for developing mental health services suitable to this population. This qualitative study contributes to this gap by exploring the experience of an understudied population: adult Jewish Argentinian immigrants to Israel, who as children experienced the military dictatorship in Argentina (1976-1983). Thematic textual analysis of narrative interviews revealed that in the case of participants who escaped with their parents as political exiles to Israel, political activism during childhood and adulthood can be both a risk and protective factor and affect a range of positive and negative long-term mental health outcomes including resilience and symptoms that appear as Complex Post-Traumatic Stress Disorder.

Increasing Influenza and Pneumococcal Vaccination Uptake in Seniors Using Point-of-Care Informational Interventions in Primary Care in Singapore: A Pragmatic, Cluster-Randomized Crossover Trial.

Objectives. To evaluate the effectiveness of point-of-care informational interventions in general practitioner clinics to improve influenza and pneumococcal vaccination uptake among elderly patients.Methods. We conducted a pragmatic, cluster-randomized crossover trial in 22 private general practitioner clinics in Singapore, from November 2017 to July 2018. We included all patients aged 65 years or older. Clinics were assigned to a 3-month intervention (flyers and posters encouraging vaccination) plus 1-month washout period, and a 4-month control period (usual care). Primary outcomes were differences in vaccination uptake rates between periods. Secondary outcomes were identification of other factors associated with vaccination uptake.Results. A total of 4378 and 4459 patients were included in the intervention and control periods, respectively. Both influenza (5.9% vs 4.8%; P = .047) and pneumococcal (5.7% vs 3.7%; P = .001) vaccination uptake rates were higher during the intervention period compared with the control period. On multilevel logistic regression analysis, follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 was associated with uptake of both vaccines.Conclusions. Point-of-care informational interventions likely contributed to increased influenza and pneumococcal vaccination uptake. Patients on follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 were more likely to receive influenza and pneumococcal vaccination and should be actively engaged by physicians.Trial Registration. ClinicalTrials.gov Identifier: NCT03445117.

Seasonal influenza-associated intensive care unit admission and death in tropical Singapore, 2011-2015.

BACKGROUND: Seasonal influenza can cause severe illness leading to intensive care unit (ICU) admission and death. OBJECTIVE: To define the clinical and epidemiological features of severe seasonal influenza infection and factors associated with mortality. STUDY DESIGN: A retrospective review was conducted on all patients with laboratory-confirmed influenza infection who were either admitted into the ICU or died in the two largest tertiary hospitals in Singapore from 2011-2015. RESULTS: Of 520 patients included in our study, 423 (81.3%) had influenza A infection and the rest with influenza B. Of patients with influenza A infection, 70.0% (296/423) were subtyped, of whom 24.0% (71/296) had A/H1N1pdm2009 and 76.0% (225/296) had A/H3N2. The median age of patients was 72 years (IQR 61-82). Males constituted 53.1% (276/520). Median Charlson comorbidity index score was 1 (IQR 0-3). About 70% had physical or radiological evidence of pneumonia upon admission. In-hospital mortality was 58.1% (302/520). On multiple logistic regression analysis, factors positively associated with mortality were age ≥65 years (adjusted odds ratio, aOR = 3.64, 95%CI 2.21-5.99, p < 0.001), malignancy (aOR = 2.53, 95%CI 1.12-5.73; p = 0.026), and hypoalbuminemia (aOR = 2.16, 95%CI 1.26-3.73; p = 0.005), while antiviral therapy (aOR = 0.33, 95%CI 0.17-0.63; p < 0.001) and ventilation (aOR = 0.23, 95% CI 0.13-0.39; p < 0.001) were negatively associated. CONCLUSIONS: Patients with severe seasonal influenza infection were characterized by advanced age, hypoalbuminemia and presence of pneumonia on admission. Age ≥65 years, malignancy, and hypoalbuminemia were associated with increased mortality, and antiviral therapy and ventilation with decreased mortality.

Interaction between Antibiotic Resistance, Resistance Genes, and Treatment Response for Urinary Tract Infections in Primary Care.

Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016. Cohort characteristics and antimicrobial susceptibility of cultured isolates were analyzed. Among Enterobacteriaceae isolates, early symptom resolution (within 3 days) according to antibiotic prescribed and isolate susceptibility and factors associated with antibiotic resistance were evaluated. Of 695 symptomatic patients, 299 were urine culture positive; of these 299 patients, 259 (87%) were female. Escherichia coli was the most common uropathogen (76%). Enterobacteriaceae isolates (n = 283) were highly susceptible to amoxicillin-clavulanate (86%), nitrofurantoin (87%), and fosfomycin (98%), but >20% were resistant to ciprofloxacin and co-trimoxazole. Isolates resistant to appropriate indicator antibiotics were further tested to determine proportions positive for blaCTX-M (14/26, 54%), plasmid-mediated ampC (12/24, 50%), qnr (7/69, 10%), and fos (1/6, 17%) resistance genes. A total of 67% of patients given antibiotics with susceptible isolates reported early resolution versus 45% given antibiotics with nonsusceptible isolates (P = 0.001) and 27% not treated (P = 0.018). On multivariable analysis, Indian ethnicity and diabetes mellitus were associated with amoxicillin-clavulanate resistance. Genitourinary abnormalities, UTI in the past 12 months, and hospitalization in the past 6 months were associated with ciprofloxacin and co-trimoxazole resistance. Patients given active empirical antibiotics were most likely to report early symptom resolution, but correlation with in vitro susceptibility was imperfect. Factors associated with resistance may guide the decision to obtain initial urine culture.

Factors influencing seasonal influenza vaccination uptake among health care workers in an adult tertiary care hospital in Singapore: A cross-sectional survey.

BACKGROUND: This study aimed to evaluate the factors influencing seasonal influenza vaccination uptake among different health care professional groups. METHODS: A single-center, cross-sectional survey using a standardized anonymous, self-administered questionnaire to assess knowledge, attitudes, and uptake of seasonal influenza vaccination was used. Associations between respective health care groups and vaccination acceptance were then assessed. RESULTS: In total, 3,873 health care workers completed the questionnaire. Of these, 7% were administrative staff, 17% were allied health staff, 7% were ancillary staff, 11% were medical staff, and 58% were nursing staff. The overall vaccination rate for the Southern Hemisphere 2015 influenza season was 82%. In a multivariate logistic regression model, after controlling for gender and presence of chronic disease, associated factors for accepting influenza vaccination were age, education level of bachelor degree or higher, preference for vaccination provided by mobile teams, having 1-50 patient contacts per week, and belief in the potential severity of influenza and vaccine safety (P < .05). In contrast, factors negatively associated with vaccination acceptance included being a medical staff member or allied health staff member, living with family members under the age of 16, fear of adverse reactions, and disbelief in vaccination effectiveness (P < .05). CONCLUSIONS: Although vaccine coverage in Singapore has been high, our findings provide guidance for the development of strategies to further improve vaccine coverage among different groups of health care workers.

ELD revisited: A second look at a neuropsychological impairment of working memory affecting retention of visuo-spatial material.

Neuropsychological case studies involving putative impairment of the visuo-spatial sketch-pad component of Baddeley's (1986) working memory model have been uncommon, with our own investigation of case ELD still being one of the most comprehensive to date (Hanley, Pearson, & Young, 1990; Hanley, Young, & Pearson, 1991). A recent theoretical review by Morey (2018) has offered a critique of ELD's data that has sought to cast doubt on our claim that she showed a pattern that reflects a problem with a functional component equivalent to the visuo-spatial sketch-pad. The importance of neuropsychological evidence to understanding visuo-spatial short-term memory has prompted us to revisit this case study, correct errors and misunderstandings in Morey's (2018) description of it, and provide some additional statistical information. Whilst acknowledging that cognitive neuropsychological studies will often depend on more than a single patient to offer definitive resolution of such an important issue, we show that there are compelling reasons to reject many of the claims that Morey (2018) made about ELD.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Correlation of clinical illness with viremia in Zika virus disease during an outbreak in Singapore.

BACKGROUND: The first autochthonous Zika virus (ZIKV) outbreak in Singapore was detected in August 2016. We report an analysis of the correlation of clinical illness with viremia and laboratory parameters in this Asian cohort. METHODS: We conducted a prospective longitudinal cohort study of patients with a positive blood ZIKV polymerase chain reaction (PCR) result who were admitted to Tan Tock Seng Hospital, Singapore, for isolation and management. RESULTS: We included 40 patients in our study. Rash was present in all patients, while 80% (32/40) had fever, 62.5% (25/40) myalgia, 60% (24/40) conjunctivitis and 38% (15/40) arthralgia. The median duration of viremia was 3.5 days (IQR: 3-5 days). Patients with viremia of ≥4 days were more likely to have prolonged fever compared to those with viremia of less than 4 days (95% versus 63%, p = 0.01), but had no significant correlation with other clinical signs and symptoms, or laboratory investigations. However, 21 patients (53%) had hypokalemia despite the absence of gastrointestinal symptoms. CONCLUSION: Although fever correlated with duration of viremia, 30% of patients remained viremic despite defervescence. Laboratory abnormalities such as leukopenia or thrombocytopenia were not prominent in this cohort but about half the patients were noted to have hypokalemia.

Developmental surface dysgraphia without surface dyslexia.

The case is reported of an individual (N.K.) with a developmental spelling impairment (dysgraphia) who has no apparent problems in reading. His performance therefore provides further evidence of a classical dissociation between impaired spelling and preserved reading in individuals with developmental literacy problems. The dissociation is observed when N.K. is asked to read and spell in either his first (Greek) or his second language (English). An investigation of his spelling performance revealed that his impairment was more selective than that of P.J.T. Although his spelling of regular words and nonwords was normal, N.K. had a problem in spelling words with atypical sound-letter associations despite having no problems in reading aloud or understanding the meaning of words of this kind. It is argued that N.K.'s pattern of performance can be best explained in terms of normal development of an orthographic system that allows access to the meaning and pronunciation of written words during reading. In terms of a dual-route model of spelling, his poor spelling appears to be the result of a developmental impairment that impedes access to the orthographic system from phonology and semantics. In terms of the triangle model, his poor spelling appears to be the result of a developmental impairment that affects activation of orthography from semantics.

An unusual outbreak of rotavirus G8P[8] gastroenteritis in adults in an urban community, Singapore, 2016.

BACKGROUND: An outbreak of gastroenteritis (GE) occurred in community-dwelling adults in the Central Region of urban Singapore, in May 2016. OBJECTIVES: To investigate the cause of the outbreak. STUDY DESIGN: We conducted a case-cohort study on GE patients linked to the outbreak who presented to the emergency department of a tertiary-care hospital near the outbreak area, from 18 May to 11 June 2016. Stools were tested for gastrointestinal pathogens including rotavirus antigen and positive rotavirus samples were subject to genotyping. RESULTS: A total of 57 adult GE patients, with a median age of 40 (range 18 to 84) years, were included. Predominant symptoms were diarrhoea (98.2%), vomiting (64.9%), and abdominal discomfort (38.6%). Age 65 years and above (Adjusted OR 21.78, 95% CI 1.49-318.84; P = 0.02) was the only predictor of admission, after adjusting for comorbidities and clinical severity. Molecular microbiological investigations confirmed that the outbreak was caused by a novel human-bovine reassortant strain of rotavirus G8P[8] with DS-1-like backbone. Exposure to the market in the outbreak area was strongly associated with rotavirus infection (OR 46.14; 95% CI 43.04-49.25, P < 0.01). No particular food item could be identified as the outbreak cause. CONCLUSIONS: This is the first report of an outbreak of rotavirus G8P[8] in adults in an urban community that is not waterborne. Transmission was likely through fomites in the market and its surrounding areas, via consumption or contact with contaminated food items purchased from the market, and from person-to-person. The potential for novel G8P[8] strains to cause outbreaks cannot be overemphasized.

Characterisation of bone and joint infections due to Group B Streptococcus serotype III sequence type 283.

In 2015, an epidemic of Group B Streptococcus (GBS) serotype III sequence type 283 (ST283) disease was reported in Singapore, associated with consumption of raw freshwater fish. In this study, we further characterise the characteristics of bone and joint infections associated with ST283 GBS in adults and the differences between ST283 and non-ST283 manifestations. A retrospective study of 54 inpatients with invasive GBS disease involving bones and/or joints from 2010 to 2015 was performed. Archived isolates were identified as GBS serotype III and ST283 positive using PCR methods. Clinical data were collected from a review of clinical charts. Twenty-three cases were ST283 and 31 were non-ST283. ST283 GBS patients were more likely to be of Chinese ethnicity, have lower Charlson comorbidity scores, and have fewer overall comorbidities, including diabetes mellitus with end-organ damage, peripheral vascular disease, and previous stroke, compared to non-ST283 GBS patients. ST283 patients had more oligoarthritis, with greater involvement of the knee, shoulder, and vertebrae, compared to monoarticular joint involvement in non-ST283 patients. Six patients had a unique combination of knee and shoulder joint involvement. All ST283 cases were mono-microbial, compared to a significant proportion of polymicrobial cultures in non-ST283 patients. Non-ST283 patients had a significantly longer length of stay and were more likely to undergo amputation or wound debridement. This study adds to growing evidence of a distinct clinical presentation associated with ST283 GBS, involving predominantly healthier patients without significant comorbidities, and with distinct clinical manifestations with regard to bone and joint disease.

Similarities between the irrelevant sound effect and the suffix effect.

Although articulatory suppression abolishes the effect of irrelevant sound (ISE) on serial recall when sequences are presented visually, the effect persists with auditory presentation of list items. Two experiments were designed to test the claim that, when articulation is suppressed, the effect of irrelevant sound on the retention of auditory lists resembles a suffix effect. A suffix is a spoken word that immediately follows the final item in a list. Even though participants are told to ignore it, the suffix impairs serial recall of auditory lists. In Experiment 1, the irrelevant sound consisted of instrumental music. The music generated a significant ISE that was abolished by articulatory suppression. It therefore appears that, when articulation is suppressed, irrelevant sound must contain speech for it to have any effect on recall. This is consistent with what is known about the suffix effect. In Experiment 2, the effect of irrelevant sound under articulatory suppression was greater when the irrelevant sound was spoken by the same voice that presented the list items. This outcome is again consistent with the known characteristics of the suffix effect. It therefore appears that, when rehearsal is suppressed, irrelevant sound disrupts the acoustic-perceptual encoding of auditorily presented list items. There is no evidence that the persistence of the ISE under suppression is a result of interference to the representation of list items in a postcategorical phonological store.