Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease

Background: Corticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy. Methods: We performed a retrospective medical chart review of patients with IBD aged 18–65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection. Results: During a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49–3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52–7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25–75% (AOR: 2.29; 95% CI: 1.21–4.34) and for >75% (AOR: 1.93; 95% CI: 1.19–3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period. Conclusion: We observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.

Blood pressure screening in midlife aids in prediction of dementia later in life

Background: There is substantial evidence that midlife hypertension is a risk factor for late life dementia. Our aim was to investigate if even high blood pressure at a single timepoint in midlife can predict an increased risk for all-cause dementia, Alzheimer’s disease (AD), or vascular dementia (VaD) later in life. Methods: The community-based study population comprised 30,102 dementia-free individuals from the Westmannia Cardiovascular Risk Factors Study. The participants were aged 40 or 50 years when the health examination took place in 1990–2000. Diagnose registers from both hospitals and primary healthcare centers were used to identify individuals who after inclusion to the study developed dementia. The association between midlife high blood pressure (defined as systolic blood pressure >140 and/or diastolic blood pressure >90 mmHg) at a single timepoint and dementia was adjusted for age, gender, body mass index (BMI), fasting blood glucose, education, smoking, and physical activity level. Multivariate binary cox regression analyses were used. Results: After a mean follow-up time of 24 years resulting in 662,244 person/years, 761 (2.5%) individuals had been diagnosed with dementia. Midlife high blood pressure at a single timepoint predicted all-cause dementia (hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.02–1.45) and VaD (HR: 2.10, 95% CI: 1.47–3.00) but not AD (HR: 1.06, 95% CI: 0.81–1.38). Conclusion: This study suggests that even midlife high blood pressure at a single timepoint predicts all-cause dementia and more than doubles the risk for VaD later in life independently of established confounders. Even though there was no such association with AD, this strengthens the importance of midlife health examinations in order to identify individuals with hypertension and initiate treatment.

Fertility awareness and intentions among young adults in Greece

Background: Greece has a mean age of first motherhood at 31.5 years, higher than the European average age of 29.4. Delaying conception, however, may be an important non-reversible cause of infertility. The aim of this study was to identify possible knowledge deficits regarding fertility in young adults. Methods: This was an online survey of young adults, regarding information on intention to parenthood and knowledge on issues affecting fertility. This study was conducted from February to December 2020, aiming for a representative sample of Greek men and women aged 18 and 26 years. The questionnaire was designed by a multidisciplinary group based on the Cardiff Fertility Knowledge Scale, which contained 22 multiple-choice or Likert-scale questions. Results: We obtained responses from 1875 young adults, whose mean age was 22.1 years. About 91.8% of men and 94.0% of women declared an intention to have children, out of which 44.0% wanted to have two and 29.0% three children. About 52.0 and 50.8% men and women, respectively, aimed to start a family between 31 and 35 years. Residents of rural areas and those with a lower education level more likely aimed to have children before the age of 30. The most prevalent answers for age of ideal parenthood were between 26 and 30 years for a woman and 31–35 years for a man. Smoking, alcohol consumption and sexually transmitted infections were identified as factors affecting both female and male fertility. Half of men and women, respectively, overestimated general success rates of reproductive techniques. Conclusion: The knowledge of fertility, particularly with regards to assisted reproductive techniques’ success rates, may be overestimated as more young adults plan for having children after the age of 30.

The profile of the COvid-19 VACcination register SAFEty study in Sweden (CoVacSafe-SE)

Background: The coronavirus disease 2019 (COVID-19) vaccines have been rapidly implemented in national vaccination programs world-wide after accelerated approval processes. The large population exposure achieved in very short time requires systematic monitoring of safety. The Swedish Medical Products Agency has launched a project platform for epidemiological surveillance to detect and characterise suspected adverse effects of COVID-19 vaccines in Sweden. Methods: The platform includes all individuals 12 years or older in Sweden in 2021 and will be updated annually. Data, including vaccine and COVID-19 disease data, socioeconomic and demographic data, comorbidity, prescribed medicines and healthcare utilisation outcomes, are obtained from several national registers in collaboration with other Swedish Government agencies. Data from 2015 to 2019 are used as a historical comparison cohort unexposed to both the COVID-19 pandemic and to the COVID-19 vaccines. Results: The primary study cohort includes 8,305,978 adults 18 years and older permanently residing in Sweden on 31 December 2020. The historical control cohort includes 8,679,641 subjects. By 31 July 2021, around 50% of those 18 years and older and two-thirds of those 50 years and older were vaccinated with at least one dose, 90% of those 70 years or older had two doses. Conclusions: The nationwide register-based study cohort created by the Swedish Medical Products Agency with regular updates of individual level linkage of COVID-19 vaccination exposure data to other health data registers will facilitate both safety signal detection and evaluation and other pharmacoepidemiological studies.

Assessing the relationship between systemic immune-inflammation index and mortality in patients with hypertrophic cardiomyopathy

Background: This study investigates the predictive value of the systemic immune-inflammation index (SII), which was calculated as platelet × neutrophil/lymphocyte ratio, for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM). Methods: A total of 360 HCM patients were enrolled. They were divided into three groups based on the tertiles of baseline SII. The association between SII and all-cause mortality was analyzed. Results: There were 53 HCM patients who died during a mean follow-up time of 4.8 years (min: 6 days and max: 10.8 years), and the mortality rate was 3.0 per 100 person years. The cumulative mortality rate was significantly different among the three tertiles of SII (P = 0.004), and the mortality rate in tertile 3 was much higher than that in the first two tertiles. In reference to tertile 1, the fully adjusted hazard ratios of all-cause mortality were 1.02 for the tertile 2 (95% confidence interval [CI]: 0.45–2.31, P = 0.966) and 2.31 for tertile 3 (95% CI: 1.10–4.87, P = 0.027). No significant interactions between SII and other variables were observed during subgroup analysis. The discriminative power was better for mid-term outcome than that for short-term or long-term outcomes. Sensitivity analyses including patients with normal platelet and white blood cell count have revealed similar results. Conclusion: SII was a significant risk factor for all-cause mortality in HCM patients. However, the discriminative power was poor to moderate. It could be used in combination with other risk factors in mortality risk stratification in HCM.

Accuracy in detecting major depressive episodes in older adults using the Swedish versions of the GDS-15 and PHQ-9

Objectives: The purpose of this study was to evaluate the diagnostic accuracy at different cut-off values for the Swedish versions of the 15-item Geriatric Depression Scale (GDS-15) and Patient Health Questionnaire (PHQ-9) compared with a structured clinical psychiatric interview in older adults. Methods: Community-dwelling participants (N = 113) aged 65 years or older completed the Swedish versions of the GDS-15 and PHQ-9 and were then interviewed using the Mini International Neuropsychiatric Interview (MINI) to establish the presence or absence of current major depressive episodes (MDEs). Areas under the curve (AUC) were calculated for each scale, as well as the sensitivity, specificity, and Youden’s index for different cut-off values. Results: Seventeen participants met the criteria for MDEs. The AUC was 0.97 for the GDS-15 and 0.95 for the PHQ-9. A cut-off of ≥6 on the GDS-15 yielded a sensitivity of 94%, a specificity of 88%, and a Youden’s index of 0.82. A cut-off of ≥5 on the PHQ-9 yielded a sensitivity of 100%, a specificity of 81%, and a Youden’s index of 0.81. The proposed cut-off of ≥10 on the PHQ-9 produced excellent specificity of 95% but a lower sensitivity of 71%. Conclusions: This study indicates that the Swedish versions of the GDS-15 and PHQ-9 have comparable accuracy as screening instruments for older adults with MDEs. However, the proposed cut-off of 10 on the PHQ-9 might be too high when applied to older individuals in Sweden, and further investigations in larger samples in different healthcare settings are warranted.

Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation

Background: Gastric nitric oxide (NO) production in response to Helicobacter pylori via inducible nitric oxide synthase (iNOS) is suggested as a biomarker of inflammation and cytotoxicity. The aim of this study was to investigate relationships between gastric [NO], immunological biomarkers and histopathology. Materials and methods: Esophagogastroduodenoscopy was done in 96 dyspepsia patients. Luminal [NO] was measured by chemiluminescence. Biopsies were taken from gastric antrum and corpus for culture and histopathology. H. pylori IgG was detected by immunoblot assay. Biobanked plasma from 76 dyspepsia patients (11 H. pylori positives) was analyzed for 39 cytokines by multiplexed ELISA. Results: H. pylori-positive patients had higher [NO] (336 ± 26 ppb, mean ± 95% CI, n = 77) than H. pylori-negative patients (128 ± 47 ppb, n = 19) (P < 0.0001). Histopathological changes were found in 99% of H. pylori-positive and 37% of H. pylori-negative patients. Histopathological concordance was 78–100% between corpus and antrum. Correlations were found between gastric [NO] and severity of acute, but not chronic, inflammation. Plasma IL-8 (increased in H. pylori positives) had greatest difference between positive and negative groups, with eotaxin, MIP-1β, MCP-4, VEGF-A, and VEGF-C also higher (P < 0.004 to P < 0.032). Diagnostic odds ratios using 75% cut-off concentration were 7.53 for IL-8, 1.15 for CRP, and 2.88 for gastric NO. Conclusions: Of the parameters tested, increased gastric [NO] and circulating IL-8 align most consistently and selectively in H. pylori-infected patients. Severity of mucosal inflammatory changes is proportional to luminal [NO], which might be tied to IL-8 production. It is proposed that IL-8 be further investigated as a blood biomarker of treatment outcomes.

The association between BMI and 90-day mortality in patients with and without diabetes seeking care at the emergency department

Background: The impact of body mass index (BMI) on mortality varies with age and disease states. The aim of this research study was to analyse the associations between BMI categories and short- and long-term mortality in patients with or without diabetes seeking care at the emergency department (ED) with acute dyspnoea. Population and methods: Patients aged ≥18 years at ED during daytime on weekdays from March 2013 to July 2018 were included. Participants were triaged according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A), and blood samples were collected. Totally, 1,710 patients were enrolled, with missing values in 113, leaving 1,597 patients, 291 with diabetes and 1,306 without diabetes. The association between BMI and short-term (90-day) and long-term (mean follow-up time 2.1 years) mortality was estimated by Cox regression with normal BMI (18.5–24.9) as referent category, with adjustment for age, sex, METTS-A scoring, glomerular filtration rate, smoking habits and cardiovascular comorbidity in a fully adjusted model. The Bonferroni correction was also used. Results: Regarding long-term mortality, patients with diabetes and BMI category ≥30 kg/m2 had a fully adjusted Hazard Ratio (HR) of 0.40 (95% confidence interval [CI]: 0.23–0.69), significant after the Bonferroni correction. Amongst patients without diabetes, those with underweight had an increased risk but only of borderline significance, whilst risks in those with overweight or obesity did not differ from reference. Regarding short-term mortality, risks did not differ from reference amongst patients with or without diabetes. Conclusions: We found divergent long-term mortality risks in patients with and without diabetes, with lower risk in obese patients (BMI ≥ 30 kg/m2) with diabetes, but no increased risk for patients without diabetes and overweight (BMI: 25–29.9 kg/m2) and obesity.