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BACKGROUND: Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels. It is associated with fatty liver disease and elevated liver function tests (LFT) in cross-sectional studies, but data from cohort studies are scarce.

AIM: To investigate the association between insulin and pathological LFT, liver disease, and cirrhosis in a population-based retrospective cohort study.

METHODS: Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used. LFT were obtained at two time points 8 years to 24 years after baseline. Liver disease diagnoses were obtained from nationwide registries. The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.

RESULTS: Total follow-up was 54054 person-years for women and 27556 person-years for men. Insulin levels were positively correlated with elevated LFT during follow-up, whereas physical activity and coffee consumption were negatively correlated. Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease, adjusted hazard ratio (aHR) of 4.3 (95%CI: 1.6-14.6) and cirrhosis (aHR = 4.8, 95%CI: 1.6-14.6).

CONCLUSION: This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease. The results support the concept of metabolic dysfunction associated liver disease.

BACKGROUND:  "Direct-to-consumer (DTC) telemedicine" is increasing worldwide and changing the map of primary health care (PHC). Virtual care has increased in the last decade and with the ongoing COVID-19 pandemic, patients' use of online care has increased even further. In Sweden, online consultations are a part of government-supported health care today, and there are several digital care providers on the Swedish market, which makes it possible to get in touch with a doctor within a few minutes. The fast expansion of this market has raised questions about the quality of primary care provided only in an online setting without any physical appointments. Antibiotic prescribing is a common treatment in PHC.

OBJECTIVE:  This study aimed to compare antibiotic prescribing between digital PHC providers (internet-PHC) and traditional physical PHC providers (physical-PHC) and to determine whether prescriptions for specific diagnoses differed between internet-PHC and physical-PHC appointments, adjusted for the effects of attained age at the time of appointment, gender, and time relative to the COVID-19 pandemic.

METHODS:  Antibiotic prescribing data based on Anatomical Therapeutic Chemical (ATC) codes were obtained for Region Sörmland residents from January 2020 until March 2021 from the Regional Administrative Office. In total, 160,238 appointments for 68,332 Sörmland residents were included (124,398 physical-PHC and 35,840 internet-PHC appointments). Prescriptions issued by internet-PHC or physical-PHC physicians were considered. Information on the appointment date, staff category serving the patient, ICD-10 (International Statistical Classification of Diseases, Tenth Revision) diagnosis codes, ATC codes of prescribed medicines, and patient-attained age and gender were used.

RESULTS:  A total of 160,238 health care appointments were registered, of which 18,433 led to an infection diagnosis. There were large differences in gender and attained age distributions among physical-PHC and internet-PHC appointments. Physical-PHC appointments peaked among patients aged 60-80 years while internet-PHC appointments peaked at 20-30 years of age for both genders. Antibiotics with the ATC codes J01A-J01X were prescribed in 9.3% (11,609/124,398) of physical-PHC appointments as compared with 6.1% (2201/35,840) of internet-PHC appointments. In addition, 61.3% (6412/10,454) of physical-PHC infection appointments resulted in antibiotic prescriptions, as compared with only 25.8% (2057/7979) of internet-PHC appointments. Analyses of the prescribed antibiotics showed that internet-PHC followed regional recommendations for all diagnoses. Physical-PHC also followed the recommendations but used a wider spectrum of antibiotics. The odds ratio of receiving an antibiotic prescription (after adjustments for attained age at the time of appointment, patient gender, and whether the prescription was issued before or during the COVID-19 pandemic) during an internet-PHC appointment was 0.23-0.39 as compared with a physical-PHC appointment.

CONCLUSIONS:  Internet-PHC appointments resulted in a significantly lower number of antibiotics prescriptions than physical-PHC appointments, adjusted for the large differences in the characteristics of patients who consult internet-PHC and physical-PHC. Internet-PHC prescribers showed appropriate prescribing according to guidelines.

Objective

To study cumulative incidence and predictors of myocardial infarction (MI) in two random general population samples consisting of middle-aged Swedish men born 30 years apart.

Method

Results from the “Study of Men Born In 1913” and the “Study of Men Born In 1943”, two longitudinal cohort studies performed in the same geographic area and using the same methodology were compared. Both cohorts were followed prospectively from 50 to 70 years of age. MI was defined as first myocardial infarction, fatal or non-fatal.

Results

Men born in 1943 had a 34% lower cumulative risk of first MI [HR 0.66 (0.50–0.88), p = 0.0051] during follow-up as compared to men born in 1913. Interaction analysis showed that hypertension had a significantly higher impact on risk of MI in cohort 1943 than in cohort 1913 [HR 2.33 (95% CI 1.41–3.83)] and [HR 1.10 (0.74–1.62)], p = 0.0009 respectively. The population attributable risk for hypertension was 2.5-fold higher in the cohort of men born in 1943 as compared to men born in 1913, and diabetes mellitus and sedentary lifestyle attributed more to MI risk in cohort 1943 than in cohort 1913. On the contrary, smoking and total cholesterol have less attributable risk to MI in cohort 1943 than in cohort 1913.

Conclusion

Despite declining incident MI and improved cardiovascular prevention in general, hypertension remains an increasingly important attributable risk factor to MI together with diabetes mellitus and sedentary lifestyle over time.

Background:

Several studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation.

Methods:

Data on 10,051 individuals aged >45 years in the Vastra Gotaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register.

Results:

Hazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59-0.85; p = 0.0002) and men (HR 0.61; 95 % CI 0.52-0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or >5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four.

Conclusion:

Use of warfarin early after diagnosis in patients with CRC was associated with improved survival.

OBJECTIVES: Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other.

METHODS: Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed.

RESULTS: Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study.

CONCLUSIONS: After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y.

Introduction: Data on the prognostic value of hypertensive response to exercise in cardiovascular disease are limited. The aim was to determine whether SBP reactions during exercise have any prognostic value in relation to the long-term risk of stroke and myocardial infarction (MI).

Patients and methods: A representative cohort of men from Gothenburg, Sweden, born in 1913, who performed a maximum exercise test at age 54 years, (n = 604), was followed-up for a maximum of 44 years with regard to stroke and MI.

Results: Among the 604 men, the mean resting and maximum SBP was 141.5 (SD 18.8) and 212.1 (SD 24.6) mmHg, respectively. For maximum SBP, the risk of stroke increased by 34% (hazard ratio 1.34, 95% confidence interval 1.11-1.61) per 1-SD increase, while no risk increase was observed for MI. The highest risk of stroke among blood pressure groups was observed among men with a resting SBP of at least 140 mmHg and a maximum SBP of at least 210 mmHg with an hazard ratio of 2.09 (95% confidence interval 1.29-3.40), compared with men with a resting SBP of less than 140 mmHg and a maximum SBP of less than 210 mmHg, independent of smoking, blood glucose, cholesterol and BMI.

Conclusion: Among middle-aged men with high resting and maximum blood pressure during maximum exercise workload, an increased risk of stroke was observed but not for MI. Further studies with larger sample sizes are needed to investigate the underlying mechanisms of the increased risk of stroke among individuals with hypertensive response to exercise.

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N-2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD, i.e. incident COPD events, in relation to the presence of various respiratory symptoms. A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N-2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model. The N-2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20-2.22; p<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N-2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of similar to 70% and similar to 90% for a very steep N-2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively. The alveolar N-2-slope should be considered in the critical need for further research on early diagnosis of COPD.

Background

A high resting heart rate (RHR) is associated with an increase in adverse events. However, the long-term prognostic value in a general population is unclear. We aimed to investigate the impact of RHR, based on both baseline and time-updated values, on mortality in a middle-aged male cohort.

Methods

A random population sample of 852 men, all born in 1913, was followed from age 50 until age 98, with repeated examinations including RHR over a period of 48 years. The impact of baseline and time-updated RHR on cause-specific mortality was assessed using Cox proportional hazard models and cubic spline models.

Results

A baseline RHR of ≥ 90 beats per minute (bpm) was associated with higher all-cause mortality, as compared with an RHR of 60–70 bpm (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.17–2.19, P = 0.003), but not with cardiovascular (CV) mortality. A time-updated RHR of < 60 bpm (HR 1.41, 95% CI 1.07–1.85, P = 0.014) and a time-updated RHR of 70–80 bpm (HR 1.34, 95% CI 1.02–1.75, P = 0.036) were both associated with higher CV mortality as compared with an RHR of 60–70 bpm after multivariable adjustment. Analyses using cubic spline models confirmed that the association of time-updated RHR with all-cause and CV mortality complied with a U-shaped curve with 60 bpm as a reference.

Conclusion

In this middle-aged male cohort, a time-updated RHR of 60–70 bpm was associated with the lowest CV mortality, suggesting that a time-updated RHR could be a useful long-term prognostic index in the general population.

Objective: To compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF).

Methods: Two population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963-1994 and 1993-2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF.

Results: Eighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913.

Conclusions: Men born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

Background To evaluate the efficacy of a multidisciplinary vocational programme in sick-listed, primary health care patients as compared to matched non-programme patients.

Methods The design was a 3-year prospective population-based, matched case-control study. It was set in a large primary healthcare centre in the city of Eskilstuna, Sweden. The subjects were 943 sickness-certified patients (482 women and 461 men). 170 high-risk patients and a matched control group (n = 340) with similar risk for not returning to work within expected time, based on propensity score was created. The intervention group passed a multidisciplinary medical assessment and a coordinated vocational programme, while the control group received usual care by their general practitioner. Main outcome was sick leave conclusion and the day when it occurred.

Results The follow-up time was subdivided into four periods. During the first two periods, days 1-14 and days 15-112 after baseline, the intervention group had a significantly lower sick leave conclusion rate than the control group (hazard ratios, (HR) 0.32, 95% CI 0.20-0.51, p < 0.0001 and 0.47, 95% CI 0.35-0.64). During the third period, days 113-365, the intervention group had an insignificantly lower conclusion rate (HR 0.70, 95% CI 0.46-1.08, p = 0.10), and during the fourth follow-up period, days 366-1096, the intervention group had an insignificantly higher conclusion rate than the control group (HR 1.16, 95% CI 0.69-1.96, p = 0.58). Across the total follow-up period, the intervention group had a lower conclusion rate than the control group (HR 0.55, 95% CI 0.45-0.66, p < 0.0001).

Conclusions No positive significant effects of the rehabilitation programme on time to sick leave conclusion were found.