Effects of Tezepelumab on Quality of Life of Patients with Moderate-to-Severe, Uncontrolled Asthma: Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: To assess the effects of tezepelumab on quality of life (QoL) in patients with moderate-to-severe, uncontrolled asthma. RECENT FINDINGS: Tezepelumab improves pulmonary function tests (PFTs) and reduces the annualized asthma exacerbation rate (AAER) in patients with moderate-to-severe, uncontrolled asthma. We searched MEDLINE, Embase, and Cochrane Library from inception to September 2022. We included randomized controlled trials comparing tezepelumab versus placebo in patients aged ≥ 12 years with asthma on medium- or high-dose inhaled corticosteroids with ≥ 1 additional controller medication for ≥ 6 months and who had ≥ 1 asthma exacerbation in the 12 months before enrollment. We estimated effects measures with a random-effects model. Of 239 records identified, three studies were included, with a total of 1,484 patients. Tezepelumab significantly decreased biomarkers of T helper 2-driven inflammation, including blood eosinophil count (MD -135.8 [95% CI -164.37, -107.23]) and fractional exhaled nitric oxide (MD -9.64 [95% CI -13.75, -5.53]); improved PFTs, including pre-bronchodilator forced expiratory volume in 1 s (MD 0.18 [95% CI 0.08-0.27]); reduced the AAER (MD 0.47 [95% CI 0.39-0.56]); improved asthma-specific health-related QoL in the Asthma Control Questionnaire-6 (MD -0.33 [95% CI -0.34, -0.32]), Asthma Quality of Life Questionnaire for 12 Years and Older (MD 0.34 [95% CI 0.33, -0.35]), Asthma Symptom Diary (MD -0.11 [95% CI -0.18, -0.04]), and European Quality of Life 5 Dimensions 5 Levels Questionnaire (SMD 3.29 [95% CI 2.03, 4.55]) scores, although not clinically important; and did not change key safety outcomes, including any adverse event (OR 0.78 [95% CI 0.56-1.09]).

Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus.

OBJECTIVES: To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation. METHODS: Retrospective cohort study with propensity score matching in veterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertiles of cumulative metformin doses. RESULTS: A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%), and their mean ± standard deviation age was 69.15 ± 7.65 years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39-0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10-0.77, P = 0.013). CONCLUSIONS: This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.

Depression but not frailty contributed to a higher risk for all-cause hospitalizations in male older veterans.

INTRODUCTION: Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Depression and frailty often coexist, suggesting a bidirectional relationship that may increase the effects of each individual condition on clinical outcomes and health-care utilization in older adults. OBJECTIVE: To determine the effects of concurrent frailty and depression on all-cause hospitalizations. METHODS/DESIGN: Prospective cohort study, conducted at a Veterans Affairs (VA) Medical Center. The participants were male, community-dwelling veterans 65 years and older. From 4 January through 30 December 2016, a 46-item frailty index was generated from data obtained from the VA electronic health record. Trained staff conducted in-depth reviews of electronic health records ascertaining depression status. Patients were followed through 31 December 2017 for all-cause hospitalizations following the initial assessment of frailty. After adjusting for covariates, the association of frailty and depression with all-cause hospitalizations was determined with the Andersen-Gill model, accounting for repeated hospitalizations. RESULTS: Five hundred fifty-three male patients were part of the study, mean age 76.3 (SD = 8.2) years. One hundred eighty-one patients (32.7%) had depression diagnoses. During a median follow-up period of 530 days (interquartile range [IQR] = 245), 123 patients (22.2%) had 240 hospitalizations. Frailty status was not associated with future hospitalizations (adjusted hazard ratio [HR] = 1.61; 95% CI, 95-2.74; P > .05). Depression was associated with higher all-cause hospitalizations (adjusted HR = 1.57; 95% CI, 1.09-2.26); P = .0157). CONCLUSIONS: Depression but not frailty was significantly associated with higher rates of all-cause hospitalization. Implementing interventions that target older adults with both frailty and depression may reduce the burden of both conditions and reduce hospitalizations.

Is there an association between ageist attitudes and frailty?

BACKGROUND: Frailty is defined as a state of vulnerability to stressors that is associated with higher morbidity, mortality and healthcare utilization in older adults. Ageism is "a process of systematic stereotyping and discrimination against people because they are old." Explicit biases involve deliberate or conscious controls, while implicit bias involve unconscious processes. Multiple studies show that self-directed ageism is a risk factor for increased morbidity and mortality. The purpose of this study was to determine whether explicit ageist attitudes are associated with frailty in Veterans. METHODS: This is a cross-sectional study of Veterans 50 years and older who completed the Kogan's Attitudes towards Older People Scale (KAOP) scale to assess explicit ageist attitudes and the Implicit Association Test (IAT) to evaluate implicit ageist attitudes from July 2014 through April 2015. We constructed a frailty index (FI) of 44 variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily living) that was retrospectively applied to the time of completion of the KAOP and IAT. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with KAOP and IAT scores as the independent variables. Age, race, ethnicity, median household income and comorbidities were considered as covariates. RESULTS: Patients were 89.76% male, 48.03% White, 87.93% non-Hispanic and the mean age was 60.51 (SD = 7.16) years. The proportion of robust, pre-frail and frail patients was 11.02% (n = 42), 59.58% (n = 227) and 29.40% (n = 112) respectively. The KAOP was completed by 381 and the IAT by 339 participants. In multinomial logistic regression, neither explicit ageist attitudes (KAOP scale score) nor implicit ageist attitudes (IAT) were associated with frailty in community dwelling Veterans after adjusting for covariates: OR = .98 (95% CI = .95-1.01), p = .221, and OR:=.97 (95% CI = .37-2.53), p = .950 respectively. CONCLUSIONS: This study shows that neither explicit nor implicit ageist attitudes were associated with frailty in community dwelling Veterans. Further longitudinal and larger studies with more diverse samples and measured with other ageism scales should evaluate the independent contribution of ageist attitudes to frailty in older adults.

The association of health literacy, numeracy and graph literacy with frailty.

BACKGROUND: Frailty is a state of vulnerability to stressors which may result in high mortality, morbidity, and health-care utilization in older adults. Whether health literacy, graph literacy and numeracy are associated with frailty is unknown. AIM: To assess the association of health literacy, numeracy and graph literacy with frailty in male veterans. METHODS: This is a retrospective study of 470 cognitively intact, non-depressed veterans who completed evaluations of health literacy, numeracy and graph literacy at Miami VA facility in 2012. A 43-item frailty index was created as a proportion of all potential variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily life). Odds ratios and 95% confidence intervals were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with health literacy, numeracy, and graph literacy scores as independent variables. Age, race, ethnicity, education, socio-economic status, and comorbidities were considered as covariates. RESULTS: Patients were 100% male, 40% White, 82% non-Hispanic, mean age was 56.8 years. The proportion of robust, pre-frail and frail was 10.0%, 61.3% and 28.7%, respectively. Neither health literacy nor objective nor subjective numeracy was associated with frailty after adjustment for covariates. In contrast, higher graph literacy scores were associated with a lower risk for frailty (p = .015) even after adjusting known risk factors for frailty. DISCUSSION AND CONCLUSION: Neither health literacy nor numeracy is associated with frailty. Higher graph literacy score is associated with a lower risk for frailty even after adjusting for known risk factors for frailty.

Body Fat Distribution in Lean Individuals with Metabolic Abnormalities.

Objective: Obesity, defined as body mass index (BMI) >30 kilogram/m2 is associated with metabolic derangements, but lean individuals with BMI <25 kilogram/m2 may also have metabolic abnormalities. This study was conducted to evaluate fat distribution in metabolically unhealthy lean (MUL) individuals. Methods: Adults with BMI 18.5-24.9 kilogram/m2 had their body composition evaluated with dual-energy X-ray absorptiometry. Metabolic data were obtained from their medical records. Patients with ≥2 components of the metabolic syndrome (MetS) were considered MUL and those with ≤1 component metabolically healthy lean (MHL). Multivariable logistic regression was used to analyze the association between metabolic abnormalities and anthropometric indexes. Results: The study includes 119 subjects; 69 in MHL and 50 in the MUL group. Two groups had comparable total body fat, fat mass index, and appendicular lean mass. Indices of visceral fat were associated with increased odds of being MUL (odds ratio with 95% confidence interval): visceral adipose tissue 1.75 (1.13-2.73), trunk-to-legs fat ratio 2.28 (1.30-4.00), trunk-to-limb fat ratio 2.43 (1.37-4.32), android-to-gynoid fat ratio 1.80 (1.07-3.03), and visceral-to-total fat percentage 1.80 (1.07-3.05). Conclusion: Metabolically unhealthy subjects had increased truncal distribution of body fat without an increase in total body fat. Body morphometry in MUL was similar to that of obese individuals with MetS.

Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. OBJECTIVE: We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. RESULTS: Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. CONCLUSION: Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.

Tubal factor, cleavage stage and more than one embryo transferred were risk factors associated with ectopic pregnancy after assisted reproductive treatment.

OBJECTIVE: Ectopic pregnancy is a well-known complication following in vitro fertilization with embryo transfer; studies have questioned, however, whether there are risk factors that could be identified before the procedure. The objective of this study was to investigate the possible risk factors involved in ectopic pregnancy following in vitro fertilization. METHODS: Retrospective case-control study performed at an assisted reproduction clinic in Brazil. To select the control group, we used a 1:4 ratio. The study included 499 patients submitted to in vitro fertilization with clinical pregnancy. We collected the data from electronic records, between 2000-2019 and divided into: Group 1, ectopic pregnancy (n=90) and Group 2, intrauterine pregnancies (n=409). RESULTS: When comparing groups, the results observed were: Tubal factor infertility (35.6% vs. 21.1%, p=.005) (OR 2.0 [1.2-3.4], p=.004); Previous miscarriage history (15.1% vs. 7.1%, p<.05) (OR 2.0 [1.02-4.29], p=.044); Number of cleavage-stage embryo transfers (69.2% vs. 54.0 p=.028) (OR 1.9 [1.08-3.33], p=.025); Two or more embryos transferred (OR 2.5 [1.12-5.70], p=.025), all associated with greater ectopic pregnancy risk. Oocyte recipient patients were excluded from this analysis, but when included a difference was found when comparing the groups (9.4% (10/106) vs. 3.0% (13/434), p=.007), (OR 3.3 [1.41-7.98] p=.005); this result should be interpreted with caution because of the sample size. CONCLUSIONS: In high-risk patients, a single blastocyst transfer seems to be a reasonable approach to decrease the ectopic pregnancy risk.

The association of health literacy domains with hospitalizations and mortality.

OBJECTIVES: To determine whether health literacy, numeracy, and graph literacy are associated with all-cause hospitalizations or mortality in community-dwelling veterans. STUDY DESIGN: Retrospective cohort study. METHODS: A total of 470 community-dwelling veterans underwent evaluations of health literacy, numeracy, and graph literacy with validated instruments in 2012 and were followed until 2018. At the end of follow-up, the associations with all-cause hospitalizations and mortality were determined with the Andersen-Gill model and Cox regression multivariate analysis, respectively. RESULTS: There were no associations of health literacy, numeracy, or graph literacy with all-cause hospitalization or mortality after multivariate adjustment. In subgroup analysis, subjective numeracy was associated with hospitalizations in African Americans. Higher objective and subjective numeracy were associated with future hospitalizations only for those with a history of hospitalization. Higher graph literacy was associated with lower mortality in those with a history of hospitalization. CONCLUSIONS: This study did not show associations of health literacy, numeracy, or graph literacy scores with lower risk of all-cause hospitalization or mortality. Further research is needed with random sampling in a broader spectrum of healthcare settings to better understand what roles health literacy, numeracy, and graph literacy might play in healthcare utilization and clinical outcomes.

Is There an Association Between Metformin Exposure and Frailty?

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Frailty and type 2 diabetes mellitus share similar pathophysiological mechanisms which metformin may target. The purpose of this study was to determine whether exposure to metformin is associated with frailty in veterans. This is a cross-sectional study of veterans 65 years and older with type 2 diabetes who were screened for frailty between January 2016 and August 2017. We constructed a 44-item Frailty Index including multiple variables using a deficit accumulation framework. After adjustment for covariates, the association was calculated using binomial logistic regression models with frailty status as the outcome variable, and metformin exposure as the independent variable. Patients were 98.3% male and 56.7% White with a mean age of 72.9 (SD = 6.8) years. The proportion of robust, prefrail and frail patients was 2.9% (n = 22), 46.7 % (n = 356) and 50.5% (n = 385), respectively. In binomial logistic regression, exposure to metformin was associated with lower risk for frailty, adjusted odds ratio (OR) = .55 (95% confidence interval [CI] = .39-.77), p ≤ .001. This study shows that exposure to metformin was associated with lower risk for frailty in community-dwelling veterans.

Is vitamin D deficiency related to a higher risk of hospitalization and mortality in veterans with heart failure?

OBJECTIVES: 25-hydroxyvitamin D [25(OH)D] deficiency is related to an increase in cardiovascular risk but the association between low 25(OH)D and hospitalization and mortality in heart failure (HF) patients remains unclear. The objective of this study was therefore to determine whether 25(OH)D deficiency is associated with a higher risk of all-cause hospitalizations and mortality in veterans with HF, as well as the differential effect of frailty. STUDY DESIGN: A retrospective cohort study of veterans with HF. MAIN OUTCOME: Association between 25(OH)D deficiency and risk of hospitalization and mortality. MEASURES: 25(OH)D status was dichotomized as deficiency (<30 ng/mL) and non-deficiency (≥30 ng/mL). A 44-item Frailty Index (FI) was constructed and used to categorize patients as non-frail (FI < .21) or frail (FI ≥ .21). The association of 25(OH)D deficiency with recurrent hospitalization was analyzed through an Andersen-Gill model and the association with mortality using Cox regression. RESULTS: We identified 284 patients, of whom 141 (50 %) exhibited 25(OH)D deficiency (67.3 ±â€¯10.5 years of age). The mean 25(OH)D levels in the deficiency and non-deficiency groups were 21.3±5.9 ng/mL and 40.9 ±â€¯10.9 ng/mL, respectively. Over a median follow-up of 1136 days (IQR = 691), there were 617 hospitalizations (68 % in those with 25(OH)D deficiency) and 131 deaths (40 % in those with 25(OH)D deficiency). A significantly higher risk of hospitalization was found in patients with 25(OH)D deficiency: hazard ratio (HR) = 1.8 (95 % CI:1.3-2.5),p < 0.001. Frail veterans had a greater risk of hospitalization than non-frail veterans: HR = 1.7 (95 % CI:1.2-2.7),p < 0.05. Mortality did not show any significant association with 25(OH)D deficiency. CONCLUSIONS: 25(OH)D deficiency was an independent risk factor for hospitalization in patients with HF and the effect persisted in those with frailty.

The Association of Ageist Attitudes With All-Cause Hospitalizations and Mortality.

Background: Ageism is the systematic stereotyping and discrimination against older adults. Explicit ageism involves conscious control and implicit ageism involves unconscious processes. Studies have shown that ageist attitudes may be associated with poor clinical outcomes like hospitalizations and mortality. Objective: Determine the association of explicit and implicit ageism with all-cause hospitalizations and mortality in a sample of Veterans. Method: Retrospective cohort study of community-dwelling Veterans 50 years and older who underwent evaluations of explicit ageism using Kogan's Attitudes Toward Old People Scale and implicit ageism assessed with Implicit Association Test (IAT) during July 2014 to April 2015 and were followed until 2018. Data on all-cause hospitalizations and mortality following the initial assessment of ageism was aggregated. Results: The study included 381 participants, 89.8% male, 48.0% White, and mean age was 60.5 (SD = 7.2) years. A total of 339 completed the IAT. Over a mean follow-up of 3.2 years (SD = 0.3), 581 hospitalizations, and 35 deaths occurred. Neither explicit nor implicit ageism was associated with an increased risk for all-cause hospitalization or mortality on follow-up. Discussion: Future research may benefit from investigating whether ageist attitudes may predict all-cause hospitalizations and mortality in longitudinal studies including more diverse samples.

Effects of statin therapy in hospitalized adult COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Introduction COVID-19 is associated with endothelial activation and systemic inflammation; consequently, statins can be used in its treatment as they have anti-inflammatory, antithrombotic, and profibrinolytic properties and may interfere with COVID-19 viral entry into cells through disruption of cell membrane lipid rafts. Objective We performed a meta-analysis of randomized clinical trials that compared statin therapy to placebo or to standard care in adult patients hospitalized for COVID-19. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for all-cause mortality, hospitalization duration, and admission to the intensive care unit. Results Of the 228 studies reviewed, four studies were included, with a total of 1,231 patients, of whom 610 (49.5%) were treated with statins. There was no significant difference in all-cause mortality (odds ratio [OR] 0.96; 95% confidence interval [95%CI]: 0.61-1.51; p=0.86; I2=13%), duration of hospitalization (mean difference [MD] 0.21; 95%CI: -1.74-2.16; p=0.83; I2=92%), intensive care unit admission (OR= 3.31; 95%CI: 0.13-87.1; p=0.47; I2=84%), need for mechanical ventilation (OR= 1.03; 95%CI: 0.36-2.94; p=0.95; I2=0%), or increase in liver enzyme levels (OR= 0.58; 95%CI: 0.27-1.25; p=0.16; I2=0%) between patients treated with or without statin therapy. Conclusion Our findings suggest that in adult patients hospitalized with COVID-19, statin therapy results in no difference in clinical outcomes when compared to outcomes by placebo or standard of care. Prospero database registration: (www.crd.york.ac.uk/prospero) under the number CRD42022338283.