Tag: pubmed

Hypertension. 2023 Aug 17. doi: 10.1161/HYPERTENSIONAHA.123.21612. Online ahead of print.

ABSTRACT

BACKGROUND: This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of the relationship between measured blood pressure (BP) and cognition and thus delineate the true association between the two.

METHODS: Systolic BP (SBP) and diastolic BP polygenic risk scores (PRSs) were calculated using summary statistics from the International Consortium of Blood Pressure-Genome Wide Association Study (n=299 024). Adjusted nonlinear mixed-effects regression models were used, including a natural splines term for BP-PRS with outcomes of fluid intelligence, reaction time (RT), and composite attention score. Moderating effects of age, sex, and antihypertensive use were assessed in separate models.

RESULTS: There were 448 575 participants (mean age, 56.3 years; age range, 37-72 years) included in the analysis after genetic and neurological disease exclusions. Genetic propensity for high SBP had an approximately linear association with worsened fluid intelligence (P=0.0018). This relationship was significantly moderated by age (P<0.0001). By contrast, genetic propensity for high and low SBP and diastolic BP predicted worse attention function (P=0.0099 and P=0.0019), with high PRSs predicting worse function than low PRSs. Genetic propensity for low SBP and diastolic BP was associated with considerably worse RTs, while for high SBP-PRSs, the RT plateaued (P<0.0001). The relationships between RT and the PRSs were significantly moderated by sex (P<0.0001) and antihypertensive use (P<0.0001).

CONCLUSIONS: Genetic propensity for high and low BP impacts on midlife cognition in subtle ways and differentially affects cognitive domains. While a genetic propensity to low BP may preserve nontimed tests in midlife, it may come at a trade-off with worsened attention scores and RT.

PMID:37589153 | DOI:10.1161/HYPERTENSIONAHA.123.21612

Clin Trials. 2023 Aug 17:17407745231193137. doi: 10.1177/17407745231193137. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials.

METHODS: This study compared participants’ demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials’ using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance).

RESULTS: The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 4 (50.0%). The primary endpoint of time to hemoglobin A1c ≥7.0% was mostly concordant between the emulated trial and the published randomized controlled trial.

CONCLUSION: Despite challenges, observational methods and real-world data can be leveraged in certain important situations for a more timely evaluation of drug effectiveness and safety in more diverse and representative patient populations.

PMID:37589143 | DOI:10.1177/17407745231193137

J Am Heart Assoc. 2023 Aug 17:e030031. doi: 10.1161/JAHA.123.030031. Online ahead of print.

ABSTRACT

Background Stress experienced in a marriage or committed relationship may be associated with worse patient-reported outcomes after acute myocardial infarction (AMI), but little is known about this association in young adults (≤55 years) with AMI. Methods and Results We used data from VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), an observational cohort study that enrolled individuals aged 18 to 55 years with AMI (2008-2012). Marital stress was self-reported 1 month after AMI using the Stockholm Marital Stress Scale (categorized as absent/mild, moderate, and severe). Outcomes were physical/mental health (Short Form-12), generic health status (EuroQol-5 Dimensions), cardiac-specific quality of life and angina (Seattle Angina Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and all-cause readmission 1 year after AMI. Regression models were sequentially adjusted for baseline health, demographics (sex, age, race or ethnicity), and socioeconomic factors (education, income, employment, and insurance). Sex and marital stress interaction was also tested. Among 1593 married/partnered participants, 576 (36.2%) reported severe marital stress, which was more common in female than male participants (39.4% versus 30.4%, P=0.001). Severe marital stress was significantly associated with worse mental health (beta=-2.13, SE=0.75, P=0.004), generic health status (beta=-3.87, SE=1.46, P=0.008), cardiac-specific quality of life (beta=-6.41, SE=1.65, P<0.001), and greater odds of angina (odds ratio [OR], 1.49 [95% CI, 1.06-2.10], P=0.023) and all-cause readmissions (OR, 1.45 [95% CI, 1.04-2.00], P=0.006), after adjusting for baseline health, demographics, and socioeconomic factors. These associations were similar across sexes (P-interaction all >0.05). Conclusions The association between marital stress and worse 1-year health outcomes was statistically significant in young patients with AMI, suggesting a need for routine screening and the creation of interventions to support patients with stress recovering from an AMI.

PMID:37589125 | DOI:10.1161/JAHA.123.030031

Circ Arrhythm Electrophysiol. 2023 Aug 17:e010891. doi: 10.1161/CIRCEP.122.010891. Online ahead of print.

ABSTRACT

BACKGROUND: Pathogenic variants in genes encoding CaM (calmodulin) are associated with a life-threatening ventricular arrhythmia syndrome (calmodulinopathy). The in vivo consequences of CaM variants have not been studied extensively and there is incomplete understanding of the genotype-phenotype relationship for recurrent variants. We investigated effects of different factors on calmodulinopathy phenotypes using 2 mouse models with a recurrent pathogenic variant (N98S) in Calm1 or Calm2.

METHODS: Genetically engineered mice with heterozygous N98S pathogenic variants in Calm1 or Calm2 genes were generated. Differences between the sexes and affected genes were assessed using multiple physiological assays at the cellular and whole animal levels. Statistical significance among groups was evaluated using 1-way ANOVA or the Kruskal-Wallis test when data were not normally distributed.

RESULTS: Calm1^N98S/+ (Calm1^S/+) or Calm2 ^N98S/+ (Calm2^S/+) mice exhibited sinus bradycardia and were more susceptible to arrhythmias after exposure to epinephrine and caffeine. Male Calm1^S/+ mice had the most severe arrhythmia phenotype with evidence of early embryonic lethality, greater susceptibility for arrhythmic events, frequent premature beats, corrected QT prolongation, and more heart rate variability after epinephrine and caffeine than females with the same genotype. Calm2^S/+ mice exhibited a less severe phenotype, with female Calm2^S/+ mice having the least severe arrhythmia susceptibility. Flecainide was not effective in preventing arrhythmias in heterozygous CaM-N98S mice. Intracellular Ca²⁺ transients observed in isolated ventricular cardiomyocytes from male heterozygous CaM-N98S mice had lower peak amplitudes and slower sarcoplasmic reticulum Ca²⁺ release following in vitro exposure to epinephrine and caffeine, which were not observed in cardiomyocytes from heterozygous female CaM-N98S mice.

CONCLUSIONS: We report heterogeneity in arrhythmia susceptibility and cardiomyocyte Ca²⁺ dynamics among male and female mice heterozygous for a recurrent pathogenic variant in Calm1 or Calm2, illustrating a complex calmodulinopathy phenotype in vivo. Further investigation of sex and genetic differences may help identify the molecular basis for this heterogeneity.

PMID:37589122 | DOI:10.1161/CIRCEP.122.010891

Pol Merkur Lekarski. 2023;51(3):250-254. doi: 10.36740/Merkur202303111.

ABSTRACT

OBJECTIVE: Aim: To study the risk factors in patients with prediabetes that can lead to the progression of impaired glucose tolerance in the form of type 2 diabetes mellitus.

PATIENTS AND METHODS: Materials and methods: The selection of patients for this study was carried out on an outpatient basis at the Department of Therapy and Family Medicine, Uzhhorod National University. Patients with prediabetes were identified based on the American Diabetes Association criteria. Informed consent was obtained from all patients before the start of the study. Patients were randomly assigned to one of two groups: Group 1 (n=37) that received typical treatment according to the recommendations of the American Diabetes Association and the control Group 2 (n=42). At the 3rd year of the study, we determined the body mass index, glucose levels and glycated hemoglobin levels of the patients, also their medical documentation was analyzed and patients were interviewed about concomitant diseases.

RESULTS: Results: Analyzing the 3-year follow-up of patients with prediabetes, cases of type 2 diabetes mellitus were detected in both groups, but there is no statistically significant difference when comparing the indicators between the groups (p>0.05).

CONCLUSION: Conclusions: In our study, we analyzed the risk factors in patients with prediabetes that can lead to type 2 diabetes. During a 3-year follow-up, we identified cases of type 2 diabetes mellitus.

PMID:37589111 | DOI:10.36740/Merkur202303111

Pol Merkur Lekarski. 2023;51(3):245-249. doi: 10.36740/Merkur202303110.

ABSTRACT

OBJECTIVE: Aim: To study the risk factors in patients with prediabetes that can lead to the progression of impaired glucose tolerance in the form of type 2 diabetes mellitus.

PATIENTS AND METHODS: Materials and methods: The selection of patients for this study was carried out on an outpatient basis at the Department of Therapy and Family Medicine, Uzhhorod National University. Patients with prediabetes were identified based on the American Diabetes Association criteria. Informed consent was obtained from all patients before the start of the study. Patients were randomly assigned to one of two groups: Group 1 (n=37) that received typical treatment according to the recommendations of the American Diabetes Association and the control Group 2 (n=42). At the 3rd year of the study, we determined the body mass index, glucose levels and glycated hemoglobin levels of the patients, also their medical documentation was analyzed and patients were interviewed about concomitant diseases.

RESULTS: Results: Analyzing the 3-year follow-up of patients with prediabetes, cases of type 2 diabetes mellitus were detected in both groups, but there is no statistically significant difference when comparing the indicators between the groups (p>0.05).

CONCLUSION: Conclusions: In our study, we analyzed the risk factors in patients with prediabetes that can lead to type 2 diabetes. During a 3-year follow-up, we identified cases of type 2 diabetes mellitus.

PMID:37589110 | DOI:10.36740/Merkur202303110

Pol Merkur Lekarski. 2023;51(3):228-233. doi: 10.36740/Merkur202303107.

ABSTRACT

OBJECTIVE: Aim: The investigation of health professionals’ burnout and depression, working in refugees’ reception centers and their possible intercorrelation.

PATIENTS AND METHODS: Materials and methods: A descriptive correlation study was carried out in health professionals, who worked in refugees’ reception centers and accommodation programs throughout Greece. Data were collected using an anonymous questionnaire through online Google Forms. The questionnaire contained demographics, the Copenhagen Burnout Questionnaire (CBI-Gr) and the Patient Health Questionnaire (PHQ-9). The SPSS 22.00 was used for the statistical analysis and the significance level was set at 0.05.

RESULTS: Results: The sample consisted of 125 healthcare professionals working in refugees’ reception centers and accommodation programs, the majority of tchem were women (62.4%), aged between 30-39 years (39.2%) nurses (24.8%) and with a master’s degree (28%). A strong linear positive correlation was found between depression and burnout (r=0.542, p=0.000). A statistically significant correlation was also recorded between burnout and female gender (p=0.001), the age group of 30-39 (p=0.042) and nursing profession (p=0.003).

CONCLUSION: Conclusions: A strong linear relationship between burnout and depression was revealed, a finding indicating that it is imperative to implement interventions to strengthen the resilience of health professionals working in refugees’ reception centers.

PMID:37589107 | DOI:10.36740/Merkur202303107

Pol Merkur Lekarski. 2023;51(3):216-220. doi: 10.36740/Merkur202303105.

ABSTRACT

OBJECTIVE: Aim: Determination of factors associated with frailty syndrome (FS) in patients with heart failure (HF).

PATIENTS AND METHODS: Materials and methods: Consecutive patients hospitalized in the department were assessed for the presence of FS using L. Fried criteria, Edmonton Frail Scale (EFS) and Tilburg Frailty Indicator (TFI). Presence of arterial hypertension, diabetes, obesity, chronic obstructive pulmonary disease (COPD), and heart failure was included in the analysis based on patients’ medical history and findings from current hospitalization. Patients were assessed for the presence of depression using Beck’s Depression Inventory (BDI). Physical capacity was assessed using NYHA classification.

RESULTS: Results: 87 patients (mean age 81.4±6.7; 57 women; 11 HFrEF, mean NYHA 2.36±1.21; 11 HFmrEF, mean NYHA 2.18±1.08; 65 HFpEF mean NYHA 1.94±1.09) were included in the analysis. Multivariable analysis showed significant relationship between FS assessed with EFS and age (β=0.316, SE=0.08; p=0.0001), arterial hypertension (β=-0.194, SE=0.08; p=0.0173), COPD (β=0.176, SE=0.08; p=0.0300) and depression (β=0.565, SE=0.08; p=0.0000). FS assessed with L. Fried criteria was significantly related to age (β=0.359, SE=0.09; p= 0.0001), NYHA classification (β= 0.336, SE=0.09; p=0.0002) and depression (β=0.297, SE=0.09; p=0.0010). Age (β=0.251, SE=0.10; p=0.0114) and depression (β=0.375, SE=0.1; p=0.0002) were significantly related to FS assessed using TFI. In multivariable analysis HF phenotype was not significantly related to FS.

CONCLUSION: Conclusions: Age and depression assessed with BDI are related to FS in patients with HF. Arterial hypertension and COPD are linked to FS assessed using EFS, whereas NYHA classification is linked to FS assessed with L. Fried criteria. No statistically significant relationship was found between FS and HF phenotype.

PMID:37589105 | DOI:10.36740/Merkur202303105

Pol Merkur Lekarski. 2023;51(3):201-206. doi: 10.36740/Merkur202303103.

ABSTRACT

OBJECTIVE: Aim: To evaluate primary health physicians’ clinical and behavioral practices towards antibiotics administration in a specific region in Greece.

PATIENTS AND METHODS: Materials and methods: A cross sectional study was conducted using a questionnaire in all structures of primary health care (PHC) of the Peloponnese Region. The study was conducted in May-October 2020.

RESULTS: Results: In total, 306 out of 404 primary healthcare physicians completed the questionnaire (response rate of 75.8%). Our results showed that most of physicians used to prescribing antibiotics empirically in common diseases, except for the prevention of secondary respiratory tract infection. Overall, 66.3% answered that they do not feel diagnostic uncertainty that would lead them to prescribe antibiotics. Approximately 40% of the physicians stated an increase on antibiotics use and patients demand for antibiotic prescribing, however 71.4% “rarely/never” affected by this requirement. 51.9% of the sample used to prescribed brand name antibiotics. Statistically significant differences were found between demographic and professional characteristics, and physicians’ clinical and behavioral practices (p≤ 0.05).

CONCLUSION: Conclusions: Our findings could provide decision makers with information on how to manage antibiotic prescribing in primary health care in the country, focusing mainly on the use of specific diagnostic tests as well as relevant guidelines and protocols for changing prescription behavior.

PMID:37589103 | DOI:10.36740/Merkur202303103

Pediatrics. 2023 Aug 17:e2023061607. doi: 10.1542/peds.2023-061607. Online ahead of print.

ABSTRACT

BACKGROUNDAND OBJECTIVES: Despite being preventable, neonatal hypothermia remains common. We hypothesized that the proportion of newborns with hypothermia on admission would be high in all settings, higher in hospitals in middle-income countries (MIC) compared with high-income countries (HIC), and associated with morbidity and mortality.

METHODS: Using the Vermont Oxford Network database of newborns with birth weights 401 to 1500 g or 22 to 29 weeks’ gestational age from 2018 to 2021, we analyzed maternal and infant characteristics, delivery room management, and outcomes by temperature within 1 hour of admission to the NICU in 12 MICs and 22 HICs.

RESULTS: Among 201 046 newborns, hypothermia was more common in MIC hospitals (64.0%) compared with HIC hospitals (28.6%). Lower birth weight, small for gestational age status, and prolonged resuscitation were perinatal risk factors for hypothermia. The mortality was doubled for hypothermic compared with euthermic newborns in MICs (24.7% and 15.4%) and HICs (12.7% and 7.6%) hospitals. After adjusting for confounders, the relative risk of death among hypothermic newborns compared with euthermic newborns was 1.21 (95% confidence interval 1.09-1.33) in MICs and 1.26 (95% confidence interval 1.21-1.31) in HICs. Every 1°C increase in admission temperature was associated with a 9% and 10% decrease in mortality risk in MICs and HICs, respectively.

CONCLUSIONS: In this large sample of newborns across MICs and HICs, hypothermia remains common and is strongly associated with mortality. The profound burden of hypothermia presents an opportunity for strategies to improve outcomes and achieve the neonatal 2030 Sustainable Development Goal.

PMID:37589082 | DOI:10.1542/peds.2023-061607