Avoiding bias in self-controlled case series studies of coronavirus disease 2019.
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ABSTRACT:
SUBMITTER: Fonseca-Rodriguez O
PROVIDER: S-EPMC8661887 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The self-controlled case series (SCCS) method is useful for estimating the relative incidence (RI) of acute events, such as adverse events (AEs) during a specified risk period following an exposure (e.g., 6-week period after vaccinations or 30-day period after infection-related hospitalizations). In practice, the "optimal" risk period is unknown and must be specified. To date, two approaches are available to guide the specification of the risk period. Both methods do not fully utilize the nature of the bias due to misspecification, which to date has not been characterized. Thus, we elucidate the bias of SCCS estimate of the RI when the risk period is misspecified. We then propose a novel method that more effectively estimates the optimal risk period and the associated RI of AEs. The new method incorporates information on the functional form of the bias. Efficacy of the proposed approach is illustrated with substantial reduction in bias and variance in simulation studies. The proposed method is illustrated with two SCCS studies to determine the (1) risk of idiopathic thrombocytopenic purpura after measles-mumps-rubella vaccination in children and (2) risk of cardiovascular events after infection-related hospitalizations in older patients on dialysis.
| S-EPMC6249026 | biostudies-literature
Project description:OBJECTIVES:To describe the risk factors for and outcomes after myoclonus in a cohort of patients with coronavirus disease 2019. DESIGN:Multicenter case series. SETTING:Three tertiary care hospitals in Massachusetts, Georgia, and Virginia. PATIENTS:Eight patients with clinical myoclonus in the setting of coronavirus disease 2019. INTERVENTIONS & MEASUREMENTS AND MAIN RESULTS:Outcomes in patients with myoclonus were variable, with one patient who died during the study period and five who were successfully extubated cognitively intact and without focal neurologic deficits. In five cases, the myoclonus completely resolved within 2 days of onset, while in three cases, it persisted for 10 days or longer. Seven patients experienced significant metabolic derangements, hypoxemia, or exposure to sedating medications that may have contributed to the development of myoclonus. One patient presented with encephalopathy and developed prolonged myoclonus in the absence of clear systemic provoking factors. CONCLUSIONS:Our findings suggest that myoclonus may be observed in severe acute respiratory syndrome coronavirus 2 infected patients, even in the absence of hypoxia. This association warrants further evaluation in larger cohorts to determine whether the presence of myoclonus may aid in the assessment of disease severity, neurologic involvement, or prognostication.
| S-EPMC7448712 | biostudies-literature
Project description:BACKGROUND:Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so "Mendelian randomization" studies using this variant as an instrumental variable could help test causality. METHODS AND FINDINGS:Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98-1.07; p?=?0.28) overall, and 1.01 (0.95-1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09-1.21), significantly discrepant (p?=?0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04-1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09-1.28) in the 72 smaller ones (total 15,498 cases). CONCLUSIONS:The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems.
| S-EPMC3283559 | biostudies-literature
Project description:Background and objectiveObservational studies may provide valuable evidence on real-world causal effects of drug effectiveness in patients with coronavirus disease 2019 (COVID-19). As patients are usually observed from hospital admission to discharge and drug initiation starts during hospitalization, advanced statistical methods are needed to account for time-dependent drug exposure, confounding and competing events. Our objective is to evaluate the observational studies on the three common methodological pitfalls in time-to-event analyses: immortal time bias, confounding bias and competing risk bias.MethodsWe performed a systematic literature search on 23 October 2020, in the PubMed database to identify observational cohort studies that evaluated drug effectiveness in hospitalized patients with COVID-19. We included articles published in four journals: British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association and The Lancet as well as their sub-journals.ResultsOverall, out of 255 articles screened, 11 observational cohort studies on treatment effectiveness with drug exposure-outcome associations were evaluated. All studies were susceptible to one or more types of bias in the primary study analysis. Eight studies had a time-dependent treatment. However, the hazard ratios were not adjusted for immortal time in the primary analysis. Even though confounders presented at baseline have been addressed in nine studies, time-varying confounding caused by time-varying treatment exposure and clinical variables was less recognized. Only one out of 11 studies addressed competing event bias by extending follow-up beyond patient discharge.ConclusionsIn the observational cohort studies on drug effectiveness for treatment of COVID-19 published in four high-impact journals, the methodological biases were concerningly common. Appropriate statistical tools are essential to avoid misleading conclusions and to obtain a better understanding of potential treatment effects.
| S-EPMC8015394 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in hypoxic respiratory failure necessitating mechanical ventilation. Barotrauma is a well-documented complication of mechanical ventilation.ObjectiveTo describe the presentation, characteristics, and management of mechanically ventilated patients with COVID-19 who developed barotrauma.MethodsRetrospective case series study of 13 adult, mechanically ventilated, laboratory-confirmed COVID-19 positive patients admitted between 3/15/2020 and 4/14/2020 to a community hospital in New York City. Patient demographics, clinical course, ventilatory parameters, and radiographic results were obtained from electronic medical records. Barotrauma was defined as pneumomediastinum, subcutaneous emphysema, and or pneumothorax on chest X-ray. Descriptive analyses and Mann-Whitney U test were performed, where appropriate.ResultsOf the 574 COVID-19 positive patients, 139 (24.2%) needed mechanical ventilation and 13 (9.4%) of those developed barotrauma. Majority of patients were Black race (92.3%), older than age 65 (56.8%), male (69.2%), and had comorbidities (76.9%). Most common presenting symptoms were cough (84.6%) and dyspnea (76.9%). Barotrauma presentations included 3/13 pneumothoraces and pneumomediastinum, 12/13 pneumomediastinum and subcutaneous emphysema, and 1/13 pneumothorax alone. The average days on ventilator was 3.4, average positive expiratory-end pressure 15.5 cmH2O, dynamic compliance 33.8 mL/cmH2O, and P/F ratio 165. Interventions were 4/13 chest tubes and 2/13 pigtail catheters.ConclusionsBarotrauma is a common complication of mechanical ventilation of COVID-19 patients. Despite high ventilatory pressures, tension pneumothorax is rare and barotrauma could potentially be managed conservatively. Further studies are needed to evaluate the indication and outcome of thoracostomies and conservative management.
| S-EPMC7750442 | biostudies-literature
Project description:BackgroundCOVID-19 caused by severe acute respiratory syndrome coronavirus 2 most commonly manifests with fever and respiratory illness. The cardiovascular manifestations have become more prevalent but can potentially go unrecognized. We look to describe cardiac manifestations in three patients with COVID-19 using cardiac enzymes, electrocardiograms, and echocardiography.Case summariesThe first patient, a 67-year-old Caucasian female with non-ischaemic dilated cardiomyopathy, presented with dyspnoea on exertion and orthopnoea 1 week after testing positive for COVID-19. Echocardiogram revealed large pericardial effusion with findings consistent with tamponade. A pericardial drain was placed, and fluid studies were consistent with viral pericarditis, treated with colchicine, hydroxychloroquine, and methylprednisolone. Follow-up echocardiograms showed apical hypokinesis, that later resolved, consistent with Takotsubo syndrome. The second patient, a 46-year-old African American male with obesity and type 2 diabetes mellitus presented with fevers, cough, and dyspnoea due to COVID-19. Clinical course was complicated with pulseless electrical activity arrest; he was found to have D-dimer and troponin elevation, and inferior wall ST elevation on ECG concerning for STEMI due to microemboli. The patient succumbed to the illness. The third patient, a 76-year-old African American female with hypertension, presented with diarrhoea, fever, and myalgia, and was found to be COVID-19 positive. Clinical course was complicated, with acute troponin elevation, decreased cardiac index, and severe hypokinesis of the basilar wall suggestive of reverse Takotsubo syndrome. The cardiac index improved after pronation and non-STEMI therapy; however, the patient expired due to worsening respiratory status.DiscussionThese case reports demonstrate cardiovascular manifestations of COVID-19 that required monitoring and urgent intervention.
| S-EPMC7314080 | biostudies-literature
Project description:BackgroundSince coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019, the number of cases has risen exponentially. Clinical characteristics and outcomes among patients with orthotopic heart transplant (OHT) with COVID-19 remain poorly described.MethodsWe performed a retrospective case series of patients with OHT with COVID-19 admitted to 1 of 2 hospitals in Southeastern Michigan between March 21 and April 22, 2020. Clinical data were obtained through review of the electronic medical record. Final date of follow-up was May 7, 2020. Demographic, clinical, laboratory, radiologic, treatment, and mortality data were collected and analyzed.ResultsWe identified 13 patients with OHT admitted with COVID-19. The mean age of patients was 61 ± 12 years, 100% were black males, and symptoms began 6 ± 4 days before admission. The most common symptoms included subjective fever (92%), shortness of breath (85%), and cough (77%). Six patients (46%) required admission to the intensive care unit. Two patients (15%) died during hospitalization.ConclusionsBlack men may be at increased risk for COVID-19 among patients with OHT. Presenting signs and symptoms in this cohort are similar to those in the general population. Elevated inflammatory markers on presentation appear to be associated with more severe illness.
| S-EPMC7224667 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is a viral infection that appeared in December 2019. The risk of infection seems to be increased in chronic inflammatory rheumatic diseases due to both immune disturbances related to the disease and treatment. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Among these patients, 3 had rheumatoid arthritis and 2 had systemic lupus erythematosus. Patients' age ranged between 38 and 63 years. Only one patient (SLE) had a severe subtype of COVID-19. All the patients were cured of COVID-19 and were subsequently discharged.
| S-EPMC7667518 | biostudies-literature
Project description:BackgroundCOVID-19 may induce a coagulation dysregulation resulting in a prothrombotic state with a higher risk of arterial and venous thrombosis. This abnormal thrombotic diathesis can lead to pulmonary embolism, stroke, and intracardiac thrombosis.Case summaryWe present two cases of unusual intracardiac thrombosis in patients hospitalized for COVID-19. In both cases, imaging tests (such as transthoracic echocardiography (TTE), computed tomography scan of the chest, and cardiac magnetic resonance imaging) showed evidence of unusual intracardiac thrombosis with thrombi adherent to regularly contracting walls.DiscussionThis evidence confirms that COVID-19 induces a hypercoagulable state which can result in intracardiac thrombosis. Therefore, TTE is indicated in all COVID-19 patients for early diagnosis, and prompt anticoagulant therapy is to be considered as a thromboprophylaxis strategy.
| S-EPMC7953950 | biostudies-literature
Project description:BackgroundThe clinical history and outcomes of coronavirus disease 2019 among people not hospitalized is not yet well characterized. To better inform clinical evaluation, we set out to characterize the natural history of coronavirus disease 2019 in primary health care.MethodsCase series of all patients rostered to physicians at a university-affiliated Family Medicine clinic. Cases met the Centers for Disease Control and Prevention definition of coronavirus disease 2019 from March 1 to May 21 2020.ResultsIn total, 89 patients meeting Centers for Disease Control and Prevention criteria for coronavirus disease 2019 were documented. Their average age was 55.6 years (range 6-95 years), and all but one was symptomatic. Fifty-seven cases (64%) had a polymerase chain reaction test for coronavirus disease 2019, of whom 77.2% tested positive. Thirty cases (33.7%) reported contact with a confirmed or probable case of coronavirus disease 2019. Based on the Charlson Comorbidity Index, 28 cases (31.5%) had no comorbid conditions. The median number of days from symptom onset to first polymerase chain reaction test was 6 days (interquartile range 2.3-11 days). The median duration of fever was 3.5 days (interquartile range 1-7 days). Twenty-four cases (27%) visited the Emergency Department, and 10 were admitted to hospital. The median number of days between symptom onset and first Emergency Department visit was 8 days (interquartile range 3.5-27 days).ConclusionsAt the start of this pandemic, the implementation of basic measures such as diagnostic testing was delayed. If we are to improve our control over the spread of coronavirus disease 2019, we will need to substantially reduce the time from symptom onset to diagnostic testing, and subsequent contact tracing. To minimize unnecessary Emergency Department visits, we propose a testable strategy for Family Medicine to engage with coronavirus disease 2019 patients in the acute phase of their illness.
| S-EPMC8290383 | biostudies-literature