Impact of the COVID-19 pandemic on a tertiary care public hospital in Singapore: resources and economic costs.

BACKGROUND: The COVID-19 pandemic has prompted hospitals to respond with stringent measures. Accurate estimates of costs and resources used in outbreaks can guide evaluations of responses. We report on the financial expenditure associated with COVID-19, the bed-days used for COVID-19 patients and hospital services displaced due to COVID-19 in a Singapore tertiary hospital. METHODS: We conducted a retrospective cost analysis from January to December 2020 in the largest public hospital in Singapore. Costs were estimated from the hospital perspective. We examined financial expenditures made in direct response to COVID-19; hospital admissions data related to COVID-19 inpatients; and the number of outpatient and emergency department visits, non-emergency surgeries, inpatient days in 2020, compared with preceding years of 2018 and 2019. Bayesian time-series was used to estimate the magnitude of displaced services. RESULTS: USD $41.96 million was incurred in the hospital for COVID-19-related expenses. Facilities set-up and capital assets accounted for 51.6% of the expenditure; patient-care supplies comprised 35.1%. Of the 19,611 inpatients tested for COVID-19 in 2020, 727 (3.7%) had COVID-19. The total inpatient- and intensive care unit (ICU)-days for COVID-19 patients in 2020 were 8009 and 8 days, respectively. A decline in all hospital services was observed from February following a raised disease outbreak alert level; most services quickly resumed when the lockdown was lifted in June. CONCLUSION: COVID-19 led to an increase in healthcare expenses and a displacement in hospital services. Our findings are useful for informing economic evaluations of COVID-19 response and provide some information about the expected costs of future outbreaks.

Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

INTRODUCTION: To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS: We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS: From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS: Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.

Serum Cholesterol Levels within the High Normal Range Are Associated with Better Cognitive Performance among Chinese Elderly.

OBJECTIVES: The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. DESIGN: A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. SETTING: Community-based setting in eight longevity areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study. MEASUREMENTS: Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score ≤23. RESULTS: There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62-0.84) for TC, 0.81(0.70-0.94) for LDL-C and 0.81(0.70-0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). CONCLUSIONS: These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly.

Chapter 6: assessing applicability of medical test studies in systematic reviews.

Use of medical tests should be guided by research evidence about the accuracy and utility of those tests in clinical care settings. Systematic reviews of the literature about medical tests must address applicability to real-world decision-making. Challenges for reviews include: (1) lack of clarity in key questions about the intended applicability of the review, (2) numerous studies in many populations and settings, (3) publications that provide too little information to assess applicability, (4) secular trends in prevalence and the spectrum of the condition for which the test is done, and (5) changes in the technology of the test itself. We describe principles for crafting reviews that meet these challenges and capture the key elements from the literature necessary to understand applicability.

Cost of multiple sclerosis by level of disability: a review of literature.

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

Meta-analysis: the detection of pancreatic malignancy with positron emission tomography.

BACKGROUND: Several factors contribute to the high mortality of pancreatic cancer, including limitations of diagnostic imaging. AIM: To perform a meta-analysis to assess the diagnostic accuracy of Fluro-deoxy-glucose positron emission tomography with computed tomography compared with computed tomography alone. METHODS: Articles were identified through a MEDLINE search and bibliography review. Summary estimates and receiver operating curves were calculated using Meta-Test 0.6. Publication bias and heterogeneity were assessed with a funnel plot and chi-squared test. RESULTS: The summary estimate and 95% confidence interval for sensitivity and specificity were as follows: computed tomography 81% (72-88%) and 66% (53-77%), PET after a positive computed tomography 92% (87-95%) and 68% (51-81%), PET after a negative computed tomography 73% (50-88%) and 86% (75-93%) and PET after an indeterminate computed tomography 100 and 68%. The area under the summary receiver operating curve was 0.82 for computed tomography and 0.94 for PET. There was no heterogeneity or publication bias. CONCLUSIONS: Our results suggest that although adding Fluro-deoxy-glucose positron emission tomography to the diagnostic work-up may enhance the diagnosis of pancreatic malignancy, its usefulness will vary depending upon the pretest probability of the patient, the results of computed tomography and the provider's testing thresholds. Further evaluation using a well-designed prospective study with a cost-effectiveness analysis is needed to clarify the appropriate role of Fluro-deoxy-glucose positron emission tomography.

VA Stroke Study: neurologist care is associated with increased testing but improved outcomes.

OBJECTIVE: VA Stroke Study (VASt) data were analyzed to determine whether neurologist management affected the process and outcome of care of patients with ischemic stroke. METHODS: VASt prospectively identified patients with stroke admitted to nine VA hospitals (April 1995 to March 1997). Demographics, stroke severity (Canadian Neurologic Score), stroke subtype (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), tests/procedures, and discharge status (independent, Rankin < or = 2, vs dead or dependent, Rankin 3 through 5) were compared between patients who were or were not cared for by a neurologist. RESULTS: Of 1,073 enrolled patients, 775 (neurologist care, n = 614; non-neurologist, n = 161) with ischemic stroke were admitted from home. Stroke severity (Canadian Neurologic Score 8.7 +/- 0.1 vs 8.4 +/- 0.2; p = 0.44), TOAST subtype (p = 0.55), and patient age (71.4 +/- 0.4 vs 72.4 +/- 0.7; p = 0.23) were similar for neurologists and non-neurologists. Neurologists more frequently obtained MRI (44% vs 16%; p < 0.001), transesophageal echocardiograms (12% vs 2%; p < 0.001), carotid ultrasounds (65% vs 57%; p = 0.05), cerebral angiography (8% vs 1%; p = 0.001), speech (35% vs 18%; p < 0.001), and occupational therapy (46% vs 33%; p = 0.005) evaluations. Brain CT, transthoracic echocardiogram, 24-hour ambulatory ECG use, and hospitalization durations (18.2 +/- 0.8 vs 19.7 +/- 4.1 days; p = 0.725) were similar. Neurologists' patients were less likely to be dead (5.6% vs 13.5%; OR = 0.38; 95% CI 0.22, 0.68; p = 0.001) and less likely to be dead or dependent (46.1% vs 57.1%; OR = 0.64; 95% CI 0.45, 0.92; p = 0.019) at the time of discharge. The benefit remained after controlling for stroke severity and comorbidity (OR = 0.63; 95% CI 0.42, 0.94; p = 0.025). CONCLUSION: Neurologist care was associated with more extensive testing, but similar lengths of hospitalization and improved outcomes.

Racial differences in survival post cerebral infarction among the elderly.

OBJECTIVE: To investigate whether there are differences in poststroke survival between African American and white patients, aged 65 and over, in the United States. METHODS: A biracial cohort of patients was selected from a random 20% national sample of Medicare patients (age 65 and over) hospitalized with cerebral infarction in 1991, and was followed up to a period of 3 years. The Cox regression model was used for covariate adjustment. RESULTS: A total of 47,045 patients (including 5,324 African Americans) were identified for our analysis. Compared to white patients, African American patients on average were 6% more likely to die post cerebral infarction. The subpopulation analyses further suggest that African Americans age 65 to 74 had much lower 3-year survival probabilities (15 to 20%) than their white counterparts. CONCLUSIONS: The authors find evidence of racial disparities in survival post cerebral infarction among the elderly, although the differences by race are not as great as reported elsewhere for stroke incidence and mortality. Future analyses, using more clinically detailed data, should focus especially on whether survival differences by race persist in the young-old (age 65 to 74) population.

Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria.

BACKGROUND AND PURPOSE: We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible. METHODS: In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record. RESULTS: The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95% CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction. CONCLUSIONS: Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through standardized medical record abstraction procedures. Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstraction. This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s) for the disagreement.

Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles.

BACKGROUND AND PURPOSE: The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered. METHODS: Computer simulations were based on the binomial distribution. RESULTS: We illustrate that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that the use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived with cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition. CONCLUSIONS: We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of the public health impact obtained in conjunction with the use of epidemiological and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.

Depression and other determinants of values placed on current health state by stroke patients: evidence from the VA Acute Stroke (VASt) study.

BACKGROUND AND PURPOSE: This prospective study examined the determinants of the utility (value) placed on health status among a sample of patients with acute ischemic and intracerebral hemorrhagic stroke. METHODS: Data were from the VA Acute Stroke (VASt) study, a nationwide prospective cohort of 1073 acute stroke patients admitted at any of 9 Department of Veterans Affairs Medical Center sites between April 1, 1995, and March 31, 1997. The primary outcome was the patient's health status utility as measured by the time-tradeoff method. Data were obtained by telephone interviews at 1, 6, and 12 months and by medical record review. General linear mixed modeling was used to assess the effects of social, psychological, and physical factors on patients' valuations of their current health state. The analysis was confined to the 327 patients who were able to provide self-reports at >/=2 time points. RESULTS: Patients' valuations of their health state status over the initial 12 months after stroke were very stable over time, with only a slight improvement at 6 months, followed by a slight decline at 12 months. In adjusted analyses, living alone, being institutionalized, decreased physical function, and depression were independently associated with lower levels of patient health status utility over time. CONCLUSIONS: Stroke patient health status utilities are relatively stable during the initial year after stroke. In addition to physical function, psychological health and social environment are important determinants of patient health status utility. These factors need to be considered when conducting stroke decision analyses if more accurate conclusions are to be drawn regarding preferred patterns of care.

New transient ischemic attack and stroke: outpatient management by primary care physicians.

BACKGROUND: Patients with transient ischemic attack (TIA) or stroke frequently first contact their primary care physician rather than seeking care at a hospital emergency department. The purpose of the present study was to identify a group of patients seen by primary care physicians in an office setting for a first-ever TIA or stroke and characterize their evaluation and management. METHODS: Practice audit based on retrospective, structured medical record abstraction from 27 primary care medical practices in 2 geographically separate communities in the eastern United States. RESULTS: Ninety-five patients with a first-ever TIA and 81 with stroke were identified. Seventy-nine percent of those with TIA vs 88% with stroke were evaluated on the day their symptoms occurred (P =.12). Only 6% were admitted to a hospital for evaluation and treatment on the day of the index visit (2% TIA; 10% stroke; P =.03); only an additional 3% were admitted during the subsequent 30 days. Specialists were consulted for 45% of patients. A brain imaging study (computed tomography or magnetic resonance imaging) was ordered on the day of the index visit in 30% (23% TIA, 37% stroke; P =.04), regardless of whether the patient was referred to a specialist. Carotid ultrasound studies were obtained in 28% (40% TIA, 14% stroke; P<.001), electrocardiograms in 19% (18% TIA, 21% stroke; P =.60), and echocardiograms in 16% (19% TIA, 14% stroke; P =.34). Fewer than half of patients with a prior history of atrial fibrillation (n = 24) underwent anticoagulation when evaluated at the index visit. Thirty-two percent of patients (31% TIA, 33% stroke; P =.70) were not hospitalized and had no evaluations performed during the first month after presenting to a primary care physician with a first TIA or stroke. Of these patients, 59% had a change in antiplatelet therapy on the day of the index visit. CONCLUSIONS: Further primary care physician education regarding the importance of promptly and fully evaluating patients with TIA or stroke may be warranted, and barriers to implementation of established secondary stroke prevention strategies need to be carefully explored. Arch Intern Med. 2000;160:2941-2946

Setting the target for a better cervical screening test: characteristics of a cost-effective test for cervical neoplasia screening.

OBJECTIVE: To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer. METHODS: Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40-90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from $0 to $15. RESULTS: When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions. CONCLUSION: Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.

Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis.

The authors constructed a Markov model as part of a systematic review of cervical cytology conducted at the Duke University Evidence-based Practice Center (Durham, North Carolina) between October 1997 and September 1998. The model incorporated states for human papillomavirus infection (HPV), low- and high-grade squamous intraepithelial lesions, and cervical cancer stages I-IV to simulate the natural history of HPV infection in a cohort of women from ages 15 to 85 years. The age-specific incidence rate of HPV, and regression and progression rates of HPV and squamous intraepithelial lesions, were obtained from the literature. The effects of varying natural history parameters on cervical cancer incidence were evaluated by using sensitivity analysis. The base-case model resulted in a lifetime cervical cancer risk of 3.67% and a lifetime cervical cancer mortality risk of 1.26%, with a peak incidence of 81/100,000 at age 50 years. Age-specific distributions of precursors were similar to reported data. Lifetime risk of cancer was most sensitive to the incidence of HPV and the probability of rapid HPV progression to high-grade lesions (two- to threefold variations in risk). The model approximates the age-specific incidence of cervical cancer and provides a tool for evaluating the natural history of HPV infection and cervical cancer carcinogenesis as well as the effectiveness and cost-effectiveness of primary and secondary prevention strategies.