Prospective Matched Cohort Study Research Articles

Characteristics and outcomes of children with SARS-CoV-2 respiratory failure: a matched cohort study

BackgroundThere are limited data on the clinical characteristics and outcomes of critically ill children requiring mechanical ventilation for SARS-CoV-2 acute respiratory failure.MethodsWe performed a multicentre prospective matched cohort study of mechanically ventilated paediatric patients aged 2 weeks to 18 years with confirmed SARS-CoV-2 acute respiratory failure, excluding Multisystem Inflammatory Syndrome. Cases were matched at 1:4 ratio to a pre COVID-19 pandemic paediatric cohort. Age, paediatric acute respiratory distress (PARDS) category, and organ dysfunction on days 0–1 of mechanical ventilation were used to match patients.ResultsOf 53 COVID-19 subjects, 60% were male, median age was 11.1 years (interquartile range 1.6–15.7), and 89% had moderate to severe PARDS on days 0–1. Compared to 195 matched controls, more children with COVID-19 were obese, cognitively or functionally impaired at baseline, Hispanic/Latino, and had pre-existing respiratory and neurologic conditions. Observed 28-day mortality was not different, but the COVID-19 cohort experienced fewer ventilator-free days and, among survivors, longer PICU stays. More COVID-19 patients were transitioned to extracorporeal membrane oxygenation.ConclusionsChildren with COVID-19 related acute respiratory failure suffered disproportionately from chronic conditions and required more critical care support than children with acute respiratory failure without SARS-CoV-2 related infection.

The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study.

Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.

Minimal impact on the resistome of children in Botswana after azithromycin treatment for acute severe diarrhoeal disease.

Macrolide antibiotics, including azithromycin, can reduce under-five mortality rates and treat various infections in children in sub-Saharan Africa. These exposures, however, can select for antibiotic-resistant bacteria in the gut microbiota. Our previous randomized controlled trial (RCT) of a rapid-test-and-treat strategy for severe acute diarrhoeal disease in children in Botswana included an intervention (three-day azithromycin dose) group and a control group that received supportive treatment. In this prospective matched cohort study using stools collected at baseline and 60 days after treatment from RCT participants, the collection of antibiotic resistance genes or resistome was compared between groups. Certain macrolide resistance genes increased in prevalence by 13% to 55% at 60 days, without differences in gene presence between the intervention and control groups. These genes were linked to tetracycline resistance genes and mobile genetic elements. Azithromycin treatment for bacterial diarrhoea for young children in Botswana resulted in similar effects on the gut resistome as the supportive treatment and did not provide additional selective pressure for macrolide resistance gene maintenance. The gut microbiota of these children contains diverse macrolide resistance genes that may be transferred within the gut upon repeated exposures to azithromycin or co-selected by other antibiotics.

Long-term bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study

Background: Severe grief is highly distressing and prevalent up to 1 year post-death among people bereaved during the first wave of COVID-19, but no study has assessed changes in grief severity beyond this timeframe. Aim: Understand the trajectory of grief during the pandemic by reassessing grief symptoms in our original cohort 12–18 months post-death. Design: Prospective matched cohort study. Settings/participants: Family members of decedents who died in an acute care hospital between November 1, 2019 and August 31, 2020 in Ottawa, Canada. Family members of patients who died of COVID (COVID +ve) were matched 2:1 with those who died of non-COVID illness (COVID −ve) during pandemic wave 1 or immediately prior to its onset (pre-COVID). Grief was assessed using the Inventory of Complicated Grief (ICG). Results: Follow-up assessment was completed by 92% (111/121) of family members in the initial cohort. Mean ICG score on the 12–18-month assessment was 19.9 (SD = 11.8), and severe grief (ICG > 25) was present in 28.8% of participants. One-third (33.3%) had either a persistently high (>25) or worsening ICG score (⩾4-point increase between assessments). Using a modified Poisson regression analysis, persistently high or worsening ICG scores were associated with endotracheal intubation in the deceased, but not cause of death (COVID +ve, COVID −ve, pre-COVID) or physical presence of the family member in the final 48 h of life. Conclusions: Severe grief is a substantial source of psychological morbidity in the wake of the COVID-19 pandemic, persisting more than a year post-death. Our findings highlight an acute need for effective and scalable means of addressing severe grief.

Growth and Body Composition 5 y After Treatment for Severe Acute Malnutrition: A 5-y Prospective Matched Cohort Study in Ethiopian Children

BackgroundShort-term anthropometric outcomes are well documented for children treated for severe acute malnutrition (SAM). However, anthropometric recovery may not indicate restoration of healthy body composition. ObjectivesThis study aimed to evaluate long-term associations of SAM with growth and body composition of children 5 y after discharge from community-based management of acute malnutrition (CMAM). MethodsWe conducted a 5-y prospective cohort study, enrolling children aged 6 to 59 mo discharged from CMAM (post-SAM) (n = 203) and nonmalnourished matched controls (n = 202) from Jimma Zone, Ethiopia in 2013. Anthropometry and body composition (bioelectrical impedance) were assessed. Multiple linear regression models tested differences in height-for-age (HAZ), weight-for-age (WAZ), and body mass index-for-age (BAZ) z-scores; height-adjusted fat-free mass index (FFMI); and FM index (FMI) between groups. ResultsPost-SAM children had higher stunting prevalence than controls at discharge (82.2% compared with 36.0%; P < 0.001), 1 y (80.2% compared with 53.7%; P < 0.001), and 5 y postdischarge (74.2% compared with 40.8%; P < 0.001). Post-SAM children remained 5 cm shorter throughout follow-up, indicating no HAZ catch-up. No catch-up in WAZ or BAZ was observed. Post-SAM children had lower hip (-2.05 cm; 95% CI: -2.73, -1.36), waist (-0.92 cm; CI: -1.59, -0.23) and mid-upper arm (-0.64 cm; CI: -0.90, -0.42) circumferences and lower-limb length (-1.57 cm; 95% CI: -2.21, -0.94) at 5 y postdischarge. They had larger waist-hip (0.02 cm; 95% CI: 0.008, 0.033) and waist-height (0.013 cm; 95% CI: 0.004, 0.021) ratios, and persistent deficits in FFMI at discharge and 6 mo and 5 y postdischarge (P < 0.001 for all). No difference was detected in head circumference, sitting height, or FMI. ConclusionsFive y after SAM treatment, children maintained deficits in HAZ, WAZ, BAZ, and FFMI, with preservation of FMI, sitting height, and head circumference at the expense of lower-limb length, indicating a “thrifty growth” pattern. Research is urgently needed to identify effective clinical and public health interventions to mitigate these consequences of malnutrition.

The Impact of Facial Burns on Short- and Long-Term Quality of Life and Psychological Distress-A Prospective Matched Cohort Study.

Burn injuries are a major healthcare challenge worldwide, with up to 50% of all minor burns located on the head and neck. With this study, we sought to describe the effect of facial burns (FB) on health-related quality of life through a prospective and matched cohort study design. Patients completed the 36 Item Short Form (SF-36) and the Hospital Anxiety and Depression Scale (HADS). Results were analyzed based on the distribution of datasets. In total, 55 patients with FB and 55 age-and sex-matched candidates were recruited. The most common mechanism of thermal injury was burns from flames. The FB group scored lower in physical and psychological dimensions than the control group, both acutely and one year after injury. An analysis of each domain showed that subjects in the FB group trended toward improvements in their score after one-year post-burn in physical functioning (acute: 71.0 ± 29.2; one-year: 83.7 ± 23.9; p = 0.02) and bodily pain (acute: 58.5 ± 30.3; one-year: 77.9 ± 30.5; p = 0.01) domains. Additionally, the FB group had significanlyt higher scores for anxiety (FB: 4.8 ± 3.2; control: 2.5 ± 2.8; p = <0.002) and depression (FB: 3.9 ± 3.5; control: 2.1 ± 2.7; p = 0.01) compared to the control. In conclusion, facial burns are associated with physical and psychosocial deficits, as well as elevated levels of psychological distress.

Need for Neonatal Resuscitation: Does Maternal COVID-19 Affect It?

Background Maternal COVID-19 infection acquired during late pregnancy carries a potential risk for adverse neonatal outcomes. There is still a paucity of data on its effect on the transition from intrauterine to extrauterine life. Objectives The objectives of this study were to determine the impact of maternal COVID-19 infection on neonates for the risk and need for resuscitation at birth, Apgar scores at 1- and 5-minutes, and the need of NICU admission during early neonatal period. Materials and method In this hospital-based prospective matched cohort study, 100 COVID-positive pregnant women presenting for delivery were enrolled. We also included 100 non-COVID pregnant women after the best possible matching of their major baseline parameters with the study group. Neonates of both groups were followed-up till 7 days of life. Results The two groups were comparable for all baseline variables except for the mode of delivery. The requirement of neonatal resuscitation was 30% and 21% in the study and control groups (RR = 1.429; 95% CI 0.88–2.32; p = 0.149). Apgar scores at 1- and 5- minutes were also unaffected by maternal COVID-19 infection with mean scores of 8.8 ± 0.651 vs. 8.87 ± 0.562 (p = 0.42) in the study and control groups, respectively. COVID-exposed neonates had a higher incidence of NICU admission when compared with the unexposed group (RR =1.616; 95% CI 1.002–2.606; p = 0.047). Among neonates born to COVID-positive mothers, 11% demonstrated evidence of SARS-CoV-2 positivity within first 5 days of life. The risk for need of resuscitation and mean Apgar scores were comparable among SARS-CoV-2 positive and negative neonates (p &gt; 0.05). Conclusion COVID-19 infection in pregnant women is not associated with an increased risk of neonatal resuscitation.

Defining the feasibility of same day adrenalectomy - A prospective matched cohort study

BackgroundDespite technical advances, day surgery still accounts for <1 % of adrenal procedures. We investigated feasibility and safety of same day adrenalectomy (SDA). MethodsBetween We recruited 30 patients with primary hyperaldosteronism (PHA) or Cushing's syndrome (CS) into a prospective matched, single centre cohort study to evaluate the impact of exposure to a same day discharge pathway (SDA cohort; n = 10) or inpatient adrenalectomy (PIPA cohort; n = 20). We compared results to a matched cohort (n = 40) from our prospective in-patient adrenalectomy registry (RIPA cohort). ResultsMean age was 51.3 ± 8.5 years, with 43 % female, 3.3 % ASA I and 96.7 % ASA II. Lesion size was 17 ± 9 mm (range 5-40 mm). 80 % of patients presented with PHA. The predefined primary endpoint (discharge on same calendar day without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, but none of the in-patients (χ2 = 57; p < 0.0001). The secondary endpoint (discharge within 23 h of surgery without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, 90 % of PIPA (n.s.), 33 % of RIPA (33 %; χ2 = 14.6 p < 0.001), and 51.5 % of IPA patients (χ2 = 8.5 p < 0.01). Combining SDA and PIPA cohorts, 93.3 % of treatment episodes met widely used (WHO, United States) definitions of day surgery as completion of the hospital care episode within 23 h. Patients admitted for SDA were highly satisfied (100 %). ConclusionSame day discharge after adrenalectomy is feasible, safe, and well-perceived in appropriately selected patients with PHA and Cushing's syndrome.

The association between proton pump inhibitor use and risk of post-hospitalization acute kidney injury: a multicenter prospective matched cohort study

BackgroundProton Pump Inhibitors (PPI) are among the most commonly used drugs to treat acid-related gastrointestinal disorders in the USA. Although PPI use has been linked to acute interstitial nephritis, the side effects of post-hospitalization acute kidney injury (AKI) and the progression of kidney disease still are controversial. We conducted a matched cohort study to examine the associations between PPI use and the side effects, especially in post-hospitalization AKI.MethodsWe investigated 340 participants from the multicenter, prospective, matched-cohort ASSESS-AKI study, which enrolled participants from December 2009 to February 2015. After the baseline index hospitalization, follow-up visits were conducted every six months, and included a collection of self-reported PPI use by participants. Post-hospitalization AKI was defined as the percentage increase from the nadir to peak inpatient SCr value was ≥ 50% and/or absolute increase ≥ 0.3 mg/dL in peak inpatient serum creatinine compared with baseline outpatient serum creatinine. We applied a zero-inflated negative binomial regression model to test the relationship between PPI use and post-hospitalization AKI. Stratified Cox proportional hazards regression models also were conducted to examine the association between PPI use and the risk of progression of kidney disease.ResultsAfter controlling for demographic variables, baseline co-morbidities and drug use histories, there was no statistically significant association between PPI use and risk of post-hospitalization AKI (risk ratio [RR], 0.91; 95% CI, 0.38 to 1.45). Stratified by AKI status at baseline, no significant relationships were confirmed between PPI use and the risk of recurrent AKI (RR, 0.85; 95% CI, 0.11 to 1.56) or incidence of AKI (RR, 1.01; 95% CI, 0.27 to 1.76). Similar non-significant results also were observed in the association between PPI use and the risk of progression of kidney diseases (Hazard Ratio [HR], 1.49; 95% CI, 0.51 to 4.36).ConclusionPPI use after the index hospitalization was not a significant risk factor for post-hospitalization AKI and progression of kidney diseases, regardless of the AKI status of participants at baseline.

Assessment of Hypertension Complications and Health Service Use 5 Years After Implementation of a Multicomponent Intervention

There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term. To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care. In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023. Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care. Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic). A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients. In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.

Chemotherapy-induced weight gain in early-stage breast cancer: a prospective matched cohort study reveals associations with inflammation and gut dysbiosis

BackgroundEarly-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes.MethodsWe undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices.ResultsAs opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species.ConclusionsWe confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes.

Are Geriatrics-Focused Primary Care Clinics Better at Diagnosing Dementia Than Traditional Clinics? A Matched Cohort Study.

Dementia and mild cognitive impairment (MCI) are prevalent but underdiagnosed. To compare new dementia/MCI diagnosis rates in geriatrics-focused primary care clinics and traditional primary care clinics. Secondary analysis of a prospective matched cohort study that spanned 2017-2021. Community-dwelling Veterans over 65 receiving primary care in a geriatrics-focused medical home (GeriPACT) or traditional primary care home (PACT) at one of 57 Veterans Affairs sites. We excluded individuals with a documented diagnosis of dementia or MCI in the year prior to enrollment. Diagnoses obtained from EHR. Cognitive status was assessed using modified Telephone Interview for Cognitive Status (mTICS) tool. The 470 participants included in this analysis were predominantly white, non-Hispanic males with an average age of 80.3years. 9.4% of participants received a diagnosis of dementia/MCI after 24months: 11.5% in GeriPACT and 7.2% in PACT. Adjusted OR for dementia/MCI diagnosis based on GeriPACT exposure was 1.47 (95% CI 0.65-3.29). Low mTICS score (≤ 27) (OR 4.89, 95% CI 2.36-10.13) and marital status (married/partnered) (OR 1.89, CI 0.99-3.59) were independent predictors of dementia/MCI diagnosis. When stratified by cognitive status: diagnosis rates were 20.8% in GeriPACT and 16.7% in PACT among those who scored lower on the cognitive assessment (mTICS ≤ 27); 7.4% in GeriPACT and 3.6% in PACT among those who scored higher (mTICS > 27). The OR for new dementia/MCI diagnosis in GeriPACT was 1.19 (95% CI 0.49-2.91) among those with a low mTICS score and 1.85 (95% CI 0.70-4.88) among those with a higher mTICS score. Observed rates of new dementia/MCI diagnosis were higher in GeriPACT, but with considerable uncertainty around estimates. Geriatrics-focused primary care clinics may be a promising avenue for improving the detection of dementia in older adults, but further larger studies are needed to confirm this relationship.

Study design and rationale for the PAASIM project: a matched cohort study on urban water supply improvements and infant enteric pathogen infection, gut microbiome development and health in Mozambique

IntroductionDespite clear linkages between provision of clean water and improvements in child health, limited information exists about the health impacts of large water infrastructure improvements in low-income settings. Billions of...

Faster lung function decline in people living with HIV despite adequate treatment: a longitudinal matched cohort study

IntroductionChronic lung disease is common among people living with HIV (PLWH). We hypothesised that PLWH receiving antiretroviral therapy (ART) have faster lung function decline than matched controls.MethodsWe performed a prospective...

Partial versus total knee arthroplasty for isolated antero-medial osteoarthritis – An analysis of PROMs and satisfaction

This study aimed to compare the patient-reported functional outcomes and patient satisfaction after medial Unicompartmental Knee Arthroplasty (UKA) versus Total Knee Arthroplasty (TKA), performed for anteromedial osteoarthritis (AMOA) of the knee in patients from an Indian population, at a minimum 3-year follow-up. This is a prospective matched cohort study (1:2 ratio). One hundred and one UKA cases were matched to 206 TKA cases by propensity score matching for age, body mass index (BMI), gender distribution, and the Charlson Comorbidity Index (CCI). The primary outcome (Oxford knee score, OKS) was assessed at a 3-year follow-up, along with secondary outcomes (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] Score, Forgotten Joint Score (FJS), Anterior Knee Pain (Kujala) score, patient satisfaction, and revision rate at the final follow-up). The UKA group was superior to the TKA group in patient-reported functional outcomes based on the OKS (p=0.004). Using the FJS score, UKA was more likely to be a forgotten joint compared to TKA (p<0.001). However, differences in the OKS and FJS did not meet the reported minimal clinically important difference (MCID) thresholds. Quality of life (EuroQol-5D VAS scale) was found to be significantly higher in the UKA group (p<0.001). Patients in the UKA group were more likely to be very satisfied (75.2%) versus the TKA group (62.1%, p=0.023). For AMOA, UKA was associated with improved patient satisfaction compared to TKA. Although patient-reported outcome measures were statistically in favour of UKA over TKA, the differences were not clinically significant. Multicenter and randomized studies comparing the two procedures are warranted. Level-II Therapeutic.

Association between pneumonia hospitalisation and long-term risk of cardiovascular disease in Chinese adults: Aprospective cohort study.

Lower respiratory tract infections, including pneumonia, have been associated with short-term increased risk of cardiovascular disease (CVD). However, there is only limited evidence about the long-term impact of pneumonia on the cardiovascular system beyond one year. We conducted a prospective matched cohort study based on data from the China Kadoorie Biobank study of 482,017 adults who were enrolled between June 25, 2004, and July 15, 2008, and were free of CVD at baseline and before pneumonia hospitalization. A total of 24,060 patients hospitalised with pneumonia were identified until December 31, 2018, and were matched on age, sex, urban or rural areas, and decile of the frailty index to 223,875 controls. We used the piecewise Cox proportional hazards model to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for pre-specified incident CVD outcomes, including ischaemic heart disease (IHD), arrhythmia, heart failure (HF), ischaemic stroke (IS), and hemorrhagic stroke (HS), at various time intervals through 10 years after pneumonia hospitalization. Of the 247,935 pneumonia cases and controls included, the mean age (standard deviation) was 53.5 (10.4), and 40.8% (101,159) were men. During follow-up, 2389 (9.9%) pneumonia cases developed IHD, 489 (2.0%) cases developed arrhythmia, 545 (2.3%) cases developed HF, 1764 (7.3%) cases developed IS, and 348 (1.4%) cases developed HS. After adjustment for sociodemographic characteristics, lifestyle factors, health status and medication, underlying conditions, and family history of CVD, the elevated CVD risk was highest within the first 30 days after pneumonia hospitalisation, with subsequent risk reductions varying by subtypes. The elevated risk remained until the eighth year after pneumonia hospitalisation for IHD, arrhythmia, and HF, with HRs (95% CIs) of 1.48 (1.13-1.93), 2.69 (1.70-4.25), and 4.36 (2.86-6.64), respectively. The risk of stroke associated with pneumonia hospitalisation remained elevated until the seventh year for IS (HR=1.30; 95% CI: 1.04-1.63), and until the second year for HS (1.39; 1.07-1.80). The above associations were consistently observed across various characteristics of the participants. In middle-aged and older Chinese adults, pneumonia hospitalisation was associated with short- and long-term CVD risk, with the elevated risk of certain CVD outcomes persisting for up to 8 years. National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation in Hong Kong, the UK Wellcome Trust.

Prognostic factors for persistent fatigue after COVID-19: a prospective matched cohort study in primary care.

Persistent fatigue after COVID-19 is common; however, the exact incidence and prognostic factors differ between studies. Evidence suggests that age, female sex, high body mass index, and comorbidities are risk factors for long COVID. To investigate the prevalence of persistent fatigue after COVID-19 in patients with a mild infection (managed in primary care) during the first wave of the pandemic and to determine prognostic factors for persistent fatigue. This was a prospective cohort study in Dutch general practice, combining online questionnaires with data from electronic health records. Patients who contacted their GP between March and May 2020 and were diagnosed with COVID-19 during the first wave of the pandemic were included. Patients were matched to controls without COVID-19 based on age, sex, and GP practice. Fatigue was measured at 3, 6, and 15 months, using the Checklist of Individual Strength. All the participants were GP attendees and included 179 with suspected COVID-19, but who had mild COVID and who had not been admitted to hospital with COVID, and 122 without suspected COVID-19. Persistent fatigue was present in 35% (49/142) of the suspected COVID-19 group and 13% (14/109) of the non-COVID-19 group (odds ratio 3.65; 95% confidence interval = 1.82 to 7.32). Prognostic factors for persistent fatigue included low education level, absence of a partner, high neuroticism (using the Eysenck Personality Questionnaire Revised-Short Form), low resilience, high frequency of GP contact, medication use, and threatening experiences in the past. The latter three factors appeared to be prognostic factors for persistent fatigue specifically after COVID-19 infection. GP patients with COVID-19 (who were not admitted to hospital with COVID) have a fourfold higher chance of developing persistent fatigue than GP patients who had not had COVID-19. This risk is even higher in psychosocially vulnerable patients who had COVID-19.

Follow-up evaluation for norovirus asymptomatic infection among healthy adults: a prospective matched cohort study

Objectives No study has evaluated the follow-up of asymptomatic norovirus infection among healthy adults. This study compared norovirus detection rates between previously known norovirus-positive and norovirus-negative adults without diarrheal symptoms, and evaluated reinfection risk among the previously-norovirus-positive group, and new asymptomatic norovirus infection risk among the previously-norovirus-negative group after 600 days. Methods This prospective age- and sex-matched cohort study, conducted in 2019 at a Japan teaching hospital, included apparently healthy asymptomatic adults with a positive norovirus result and those with a negative result (ratio 1:3) during the 2016–2017 screening. The primary outcome was real-time reverse-transcription polymerase chain reaction-confirmed norovirus in stool specimens. We evaluated descriptive statistics and associated factors, including demographics, social habits, and clinical parameters. Results Of 288 participants [mean age, 59.9 (standard deviation: 12.6) years; male, 143 (49.7%)], 73 [genogroup (G) I 35; GII 37; both included 1 each] were positive for norovirus previously, while 215 were negative. After a median of 599 (interquartile range 515–799) days between baseline screening and follow-up, 14 (4.9%; GI 0; GII 14) tested positive for norovirus (2.7% and 5.6% among positive- and negative-norovirus groups at baseline, respectively). Among previously norovirus-negative participants, being older, having elevated blood pressure and haemoglobin A1c level, and drinking Japanese sake at baseline were associated with positive results at follow-up. Conclusions Genogroup homotypic protective effect may exist for subsequent asymptomatic infection. There may be higher risks of future asymptomatic norovirus infection in previously no-norovirus asymptomatic infection people with specific lifestyles or medical histories. SUMMARY The detection follow-up rates of norovirus were 2.7% and 5.6% among asymptomatic adults with positive- and negative-norovirus status at baseline, respectively. Specific lifestyles or medical histories may confer higher risk of norovirus detection.

Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study

Background and aimsIndividuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. MethodsThis prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. ResultsIndividuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. ConclusionsNo significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti-thrombotic medication.

No increased risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study

Background and Aims : Risk of ischemic stroke is associated with elevated concentrations of LDL-C, which is severely elevated in subjects with familial hypercholesterolemia (FH). The risk of hemorrhagic stroke is however unknown. Aim was to investigate risk of incident stroke (ischemic and hemorrhagic combined) in individuals with genetically verified FH compared with age and sex matched controls. Further, to examine the relationship between cumulative statin exposure [daily defined doses (DDD)] and risk of stroke in FH.