Risk of infections in non-alcoholic fatty liver disease: A nationwide population-based cohort study

Background and Aims

Previous literature suggests an association between non-alcoholic fatty liver disease (NAFLD) and infections. We aimed to determine the rate and risk of severe infections in NAFLD compared to the general population.

Methods

In this population-based cohort study, we used national registers to identify all patients with a hospital-based diagnosis of NAFLD in Sweden 1987–2020 (n = 14 869). The patients were matched with ≤10 comparators from the general population for age, sex, municipality, and calendar year (n = 137 145). Cox regression was used to estimate hazard ratios (HR) for infections in patients with NAFLD compared to comparators. Cumulative incidences were calculated while accounting for competing risks (non-infection death and liver transplantation).

Results

Severe infections leading to death or hospitalization occurred in 1990 (13.4%) patients with NAFLD and 9899 (7.2%) comparators during a median of 4.5 and 6.1 years of follow-up, respectively. The rate of severe infections per 1000 person-years was higher in patients with NAFLD (21.0) than comparators (9.1) independently of components related to the metabolic syndrome (adjusted HR 1.9, 95% CI = 1.8–2.0). Infection-related mortality was also higher in NAFLD compared to comparators (adjusted HR 1.8, 95% CI = 1.6–2.2). The 10-year cumulative incidence of severe infections was 16.6% (95% CI = 15.8–17.4) in NAFLD and 8.0% (95% CI = 7.8–8.2) in comparators.

Conclusion

NAFLD was associated with severe infections and infection-related mortality, independently of components associated with the metabolic syndrome. Increased clinical vigilance of severe infections in NAFLD may diminish the risk of premature death.     

Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study

BACKGROUND: Patients using higher dosages of inhaled or oral glucocorticoids (GCs) have an increased risk of hip/femur fractures. The role of the underlying disease in the aetiology of this increased risk has not been widely studied. OBJECTIVE: To evaluate the contribution of the underlying disease to the risk of hip/femur fracture in patients using inhaled or oral GCs. DESIGN AND SUBJECTS: A case-control study within the Dutch PHARMO-RLS database was conducted. Cases (n = 6763) were adult patients with a first hip/femur fracture during enrolment. Each case was matched to four controls by age, gender and region. RESULTS: The risk of hip/femur fracture increased with current use of inhaled GCs (crude OR 1.30, 95% CI:1.16-1.47) and with current use of oral GCs (crude OR 1.66, 95% CI: 1.46-1.90). After adjustment for disease severity, the risk of hip/femur fracture was no longer statistically significantly increased in inhaled GC users (adjusted OR 1.08, 95% CI: 0.91-1.27), whilst it remained elevated in oral GC users (adjusted OR 1.43, 95% CI: 1.22-1.67). Patients using inhaled GCs without any exposure to oral GCs had no increased risk of fracture (adjusted OR 0.98, 95% CI: 0.79-1.22). CONCLUSION: Inhaled GC users had no increased risk of femur/hip fracture after adjustment for underlying disease severity. Our data suggest that, even at higher dosages, inhaled GC use is not an independent risk factor for fracture. In contrast, oral GC use was associated with an increased risk of fracture, which was not fully explained by the underlying disease severity.     

Risk factors for cardiovascular disease in a Brazilian population-based cohort study

Objective: Our aim was to investigate risk factors for cardiovascular disease (CVD) in a population-based Brazilian cohort. Design and methods: A cohort study was conducted with 1091 individuals identified through multi-stage probability sampling in Porto Alegre, Brazil. Risk factors were investigated among demographic and anthropometric characteristics, including education, smoking habits, income, alcoholic beverage consumption, and blood pressure. A fatal or non-fatal episode of myocardial infarction, stroke, or heart failure, and cases of sudden death comprised the composite endpoint. Results: Vital status was determined in 982 (90.0%) of the participants of the original cohort after 6.0±1.7 years of follow-up. A total of 52 individuals presented a cardiovascular event. Male gender (hazard ratio (HR) 2.01, 95% CI 1.03–3.91), systolic blood pressure (mmHg) (HR 1.03, 95% CI 1.01–1.04) and alcohol consumption (g/day) (HR 1.001, 95% CI 1.00–1.003) were associated with the incidence of CVD after controlling for confounding. Body mass index (HR 1.05, 95% CI 0.99–1.11) and current or previous smoking (HR 1.65, 95% CI 0.83–3.26) showed a trend for a positive association. Conclusions: We confirmed that male gender, systolic blood pressure, obesity and smoking are risk factors for cardiovascular disease in a Brazilian population. The positive association between alcohol consumption and incident CVD was unexpected and deserves replication.     

Risk of inflammatory bowel disease after Campylobacter jejuni and Campylobacter concisus infection: a population-based cohort study

Objectives: In this population-based cohort study, we aimed to examine the risk of IBD following a positive stool culture with Campylobacter jejuni or Campylobacter concisus, as well as following culture-negative stool testing.

Materials and methods: Patients with a first-time positive stool culture with C. jejuni or C. concisus, as well as negative stool testing, from 2009 through 2013 in North Denmark Region, Denmark, were identified. Patients diagnosed with IBD during follow-up (to 1 March 2018) were identified using national registries. For each case, we selected ten population comparisons matched by age, gender, and calendar-time.

Results: We identified 1693 patients with C. jejuni, 910 C. concisus-positive patients, and 11,383 patients with culture-negative stools. During the first year of follow-up C. jejuni-positive patients had higher risk of IBD (HR 2.2, 95% CI 1.3–3.7) compared to population comparisons, but not after exclusion of the first year (HR 1.1, 95% CI 0.5–2.3). Campylobacter concisus-positive patients and culture-negative patients had similar risk of IBD (HR 12.9, 95% CI 7.2–22.9 and HR 8.7, 95% CI 7.5–10.2), during the first year, which decreased to (HR 3.3, 95% CI 1.3–8.5 and HR 3.2, 95% CI 2.6–4.0) after exclusion of the first year.

Conclusions: This study does not support exposure of C. jejuni or C. concisus infection as a causal trigger in subsequent development of IBD, since culture-negative patients had similar risk for IBD on long term follow-up. Additional studies including C. concisus exposures for an evaluation of the specific risk of IBD are needed.     

Mortality in inflammatory bowel disease: a population-based cohort study

BACKGROUND & AIMS: There is no consensus regarding any increase in mortality with inflammatory bowel disease (IBD). In general, previous studies were not contemporary and were unable to correct for likely confounders. We have performed a large cohort study to examine contemporary IBD related mortality in the United Kingdom. METHODS: We selected subjects within the General Practice Research Database with a coded diagnosis of inflammatory bowel disease and up to 5 matched controls for each. We derived the date of recorded deaths and information on smoking and a variety of medical conditions. We calculated both the absolute risk of death and the relative risk as a hazard ratio corrected for available confounders by Cox regression. RESULTS: We included 16,550 IBD cases with 1047 deaths and 82,917 controls with 3758 deaths. The mortality rate was 17.1 per 1000 person-years overall for IBD cases and 12.3 for controls; this difference was greatest in the elderly. Conversion of these figures to hazard ratios by Cox regression gave hazard ratios of 1.54 (1.44-1.65) for all IBD, 1.44 (1.31-1.58) for ulcerative colitis (UC), and 1.73 (1.54-1.96) for Crohn's disease. The greatest hazard ratio for UC was among the 40-59-year age group (1.79 [1.42-2.27]) and for Crohn's disease among 20-39-year-olds (3.82 [2.17-6.75]). CONCLUSIONS: IBD is associated with an overall small increase in mortality rate greatest in relative terms in younger subjects but in absolute terms in the elderly.     

Serological antibodies and surgery in a population-based inception cohort of Crohn’s disease patients – the IBSEN study

Abstract

Introduction: Serological antibodies have been associated with complicated disease course in Crohn’s disease (CD), including the need for surgery.

Aim: The aim of this study was to investigate if a panel of relevant antibodies could predict surgery in a prospective population-based cohort of patients with CD.

Methods: The population-based IBSEN cohort has been followed prospectively for 20?years. At the 10- and 20-year follow-up, the following panel of serological antibodies was analysed: pANCA, ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1. At the 20-year follow-up or until lost to follow-up, all CD-related surgeries were registered.

Results: Serum was available from 159 patients at 10-year follow-up and 135 patients at 20-year follow-up. In 113 patients, serum was available at both time points. No significant change of antibody status (positive vs. negative) was found from 10-year to 20-year follow-up. Negative pANCA, positive ASCA IgA and positive ASCA IgG at 10-year follow-up were all individually associated with increased risk for CD-related surgery. There was no association between anti-OmpC, anti-I2 or anti-CBir1 and CD-related surgery. In a multiple regression model including disease location and behaviour, only stricturing or penetrating disease behaviour and negative pANCA remained significantly associated with higher odds for surgery.

Conclusion: Positive ASCA IgA and IgG, and negative pANCA were associated with higher odds for CD-related surgery in univariate analysis. Since disease phenotype changes during the disease course, while serological antibodies are stable, our results support the use of pANCA, ASCA IgA and ASCA IgG as prognostic markers in CD.     

Personality pattern in peptic ulcer disease: a cohort study

Abstract. Objectives. To investigate the direction of a possible relationship between peptic ulcer disease and personality disorders. Design. A cohort study of 50-year old patients, observed for 2 decades. Setting. Glostrup County, Denmark (population 100000). Subjects. A representative sample of 50-year old people born in 1914 (n = 673) were followed for 20 years. All 673 filled in the Minnesota Multiphasic Personality Inventory (MMPI) in 1964 and 513 were retested with MMPI in 1974. Main outcome measures. Prevalence of peptic ulcer disease 1964, incidence of peptic ulcer disease 1964-84, MMPI scores. Results. The prevalence of peptic ulcer disease in 1964 was 7% and the average annual incidence in the period 1964-84 was 2.1 per 1000 persons. Those with incidental peptic ulcer in 1964-84 had normal MMPI scores in 1964, whilst those with peptic ulcer in 1964 had a slight but statistically significant increase in one neuroticism scale (HS) only. The group with prevalent ulcer disease in 1974 exhibited statistically significant increases in the three neuroticism scales (HS, D, HY) and in scale Pd and scale Pt at MMPI retesting. In addition they had statistically significantly higher scores in the three neuroticism scales compared with the other persons who still had normal scores in all scales. Conclusions. Personality disorders in patients with peptic ulcer are consequences of the disease and not causal factors.     

Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study

Objective: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn’s disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort.

Methods: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses.

Results: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p?<?.001, and CD 17.5 versus 13.3, p?<?.001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression.

Conclusion: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.     

Premature mortality in patients with Addison's disease: a population-based study

BACKGROUND: The survival rate of patients with primary adrenal insufficiency (Addison's disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison's disease in Sweden. METHODS: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987-2001. After a diagnosis of Addison's disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. FINDINGS: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91-2.51) for men and 2.86 (confidence interval 2.54-3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. INTERPRETATION: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison's disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.     

Risk of developing diabetes is inversely related to lung function: a population-based cohort study.

AIM: To investigate whether reduced lung function is a risk factor for developing diabetes. METHODS: Non-diabetic men (n = 382) from the population-based cohort 'Men Born in 1914' were examined with spirometry at age 55 years. The cohort was re-examined at 68 years. Diabetes and fasting plasma glucose at follow-up were studied in relation to vital capacity (VC) and forced expiratory volume (FEV1.0) at baseline. RESULTS: Fifteen men developed diabetes during the follow-up. The percentage with diabetes in the 1st, 2nd, 3rd and top quartile of vital capacity were 7%, 5%, 2%, and 1%, respectively (P for trend = 0.01). Fasting glucose (log transformed, mmol/l) at follow-up was 1.63 +/- 0.16, 1.62 +/- 0.18, 1.61 +/- 0.11 and 1.60 +/- 0.11, respectively (P for trend = 0.11). The longitudinal associations between VC and diabetes (P = 0.001) and log glucose (P = 0.036) were significant after adjustments for several potential confounders. FEV(1.0) at baseline showed similar associations with diabetes at follow-up. CONCLUSIONS: The risk of developing diabetes is inversely associated with pulmonary function among middle-aged men.     

Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: A nationwide,population-based study

BACKGROUND There is a growing evidence regarding an increased risk of inflammatory bowel disease(IBD) among patients with airway diseases.AIM To investigate the influence of chronic obstructive pulmonary disease(COPD) on the risk of IBD.METHODS A nationwide, population-based study was conducted using data from the National Health Insurance Service database. A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified. The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria. The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models. The cumulativeincidences of IBD were compared between the groups.RESULTS The COPD group had higher incidences of IBD compared to non-COPD controls(incidence rate, 9.98 vs 7.18 per 100000 person-years, P 0.001). The risk of IBD in the COPD group was increased by 1.38(adjusted hazard ratio(HR); 95%CI: 1.25-1.52). The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group(12.39 vs 9.77 per 100000 person-year, P 0.001). The severity of COPD was associated with an increased risk of IBD(adjusted HR 1.70 in severe COPD, 95%CI: 1.27-2.21 and adjusted HR 1.35 in mild COPD, 95%CI: 1.22-1.49)CONCLUSION The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.     

Risk of malignancy in scleroderma: a population-based cohort study

OBJECTIVE: To determine the incidence of cancer in patients with scleroderma (systemic sclerosis) and to compare those rates with cancer rates in the local population. METHODS: Cancer risk in scleroderma patients in the Detroit metropolitan area was assessed by linking patient identification codes of the Michigan Scleroderma Registry to the Metropolitan Detroit Cancer Surveillance System database. Patients were screened between the years 1973 and 2002, with additional followup to 2004. Standardized incidence ratios (SIRs) were calculated for selected malignancies (lung, liver, colon, breast, cervical, and prostate cancers, and non-Hodgkin's lymphomas), with stratification by sex and race. RESULTS: Of 934 patients in the Scleroderma Registry, 538 were included in the study based on tri-county residency (436 females and 102 males). Of these, 45 first malignancies were noted (37 females and 8 males). Lung cancer (10 cases) was found to be the most common cancer in scleroderma patients. However, its incidence was not significantly different from that in the general population of metropolitan Detroit (SIR 1.23). Other types of cancer were examined, and no significant differences were found as compared with the rates in the local population, with 1 exception: black females with scleroderma had significantly higher rates of liver cancer (SIR 45.8). CONCLUSION: Contrary to previous studies, this study did not find statistical evidence of an increased incidence of cancer in scleroderma patients, except for liver cancer. One possible reason is the high background rates of certain cancers in the metropolitan Detroit area. It may be necessary to consider local cancer rates when comparing different scleroderma cohorts.     

Older adults' medication use 6 months before and after hip fracture: a population-based cohort study

OBJECTIVES: To study changes in use of fall‐risk increasing drugs (FRIDs) and bone density–related medication in participants with hip fracture before and after the fracture and to analyze differences between five healthcare districts. DESIGN: Population‐based cohort study. SETTING: Data retrieved from two national databases PARTICIPANTS: All 2,043 people with hip fracture aged 60 and older in a Swedish county in 2006. MEASUREMENTS: Changes in FRIDs and bone‐active medications prescribed within 6 months before and 6 months after hip fracture and differences between health care districts. RESULTS: Before hip fracture, 1,308 participants (67.7%) received any FRIDs or combinations; after fracture, 97.7% were treated. Polypharmacy (≥5 drugs) increased 39.3%, excessive polypharmacy (≥10 drugs) increased 36.4%, and use of three or more psychotropic drugs increased 8.6%. After fracture, the use of all analyzed drugs including psychotropic, cardiovascular, opioid, and anticholinergic drugs increased significantly (P<.001). Treatment with calcium and vitamin D increased from 9% before to 27.7% after and with bisphosphonates from 3.5% to 7.6%. Variations in postfracture prescribing between the five health care districts were observed regarding opioids (range 85–64%), bisphosphonates (range 20–4%), and calcium and vitamin D (72–13%) (P<.001, for all comparisons). CONCLUSION: Two‐thirds of participants with hip fracture were prescribed FRIDs before fracture, and the number increased significantly after fracture. Significant variations between healthcare districts in treating osteoporosis and pain were evident; geriatric support could be a contributing factor to the greater treatment in two districts.     

Mortality,disability, and nursing home use for persons with and without hip fracture: a population-based study

OBJECTIVES: To compare persons with and without hip fracture for subsequent mortality and change in disability and nursing home (NH) use. DESIGN: Population-based historical cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: All residents who experienced a first hip fracture between January 1, 1989, and December 31, 1993, and, for each case, a resident of the same sex and similar age who had not experienced a hip fracture and was seen by a local care provider. MEASUREMENTS: Data on disability (Rankin score), comorbidity (Charlson Index), and NH residency before baseline (fracture date for cases and registration date for controls) were obtained by review of complete community-based medical records. The records were then reviewed from baseline through December 31, 1994, for Rankin disability at 1 month and 1 year, all NH admissions and discharges, and date of death for those who died. RESULTS: There were 312 cases and 312 controls (81% female, mean age +/- standard deviation = 81 +/- 12 years). Before baseline, cases had higher comorbidity (45% vs 30% had Charlson Index >/= 1, P <.001) and disability (mean Rankin score = 2.5 +/- 1.1 vs 2.2 +/- 1.1, P <.001) and were more likely to be in a NH (28% vs 18%, P <.001) than controls. One year after baseline, estimated mortality was 20% (95% confidence interval (CI) = 16-24) for cases vs 11% (95% CI = 8-15) for controls, 51% of cases versus 16% of controls had a level of disability one or more units worse than before baseline (P <.001), and the cumulative incidence of first NH admission was 64% (95% CI = 58-71) for cases versus 7% (95% CI = 4-11) for controls. The risk of NH admission for cases relative to controls diminished over time, but remained elevated 5 years after the event (risk ratio = 20.0 at 3 months and 2.1 at 5 years), but, in persons admitted to a nursing home, cases were two times more likely than controls to be discharged alive within a year (P <.001). CONCLUSIONS: Hip fracture is an important contributor to disability and NH use, but the potential savings from hip fracture prophylaxis may be overestimated by studies that fail to consider differential risk, mortality, and long-term follow-up.