Why Evidence Generation Should Matter to Payers and How They Can Help.

Importance: The US leads the world in bringing new medical products to market, but the ability to generate evidence to inform clinical practice in postmarket settings needs improvement. Although a diverse group of stakeholders is working to improve postmarket evidence generation, the role of private payers has been underappreciated. Observations: Payers are crucial allies in improving evidence generation because better data would better inform coverage decisions, their policies and practices influence the conduct of care and research, and their claims data are a source of real-world evidence used in medical product evaluation. In addition, payers have a stake in improving evidence generation because the kinds of evidence needed to inform health care and coverage decisions are often not available when a product enters the market and may not be generated without their involvement. Here, we describe several key steps payers could take to improve evidence generation, including participating in efforts to reduce administrative and financial barriers to the conduct of clinical trials, directly incentivizing evidence generation on high-priority questions by funding potential cost-saving trials, increasing engagement with the medical products industry on evidentiary needs for coverage decisions, and improving usability of claims data by reducing data lags and routinely recording unique device identifiers. Broad payer engagement with US Food and Drug Administration recommendations regarding evidence generation will ensure that the opportunities to participate in clinical research are extended to all communities and that evidence needed to inform care is generated in trials and surveillance systems that reflect the clinical reality across the US. Conclusions and Relevance: Increasing payer involvement in evidence generation can benefit all participants in the medical innovation ecosystem. The importance of payers in these efforts will continue to grow in response to imperatives to increase integration of care and research, engage a diverse set of communities in clinical research, and move toward alternative payment models.

Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

Regional fat distribution and hepatic fibrosis and steatosis severity in patients with nonalcoholic fatty liver disease and type 2 diabetes.

Background: Epidemiologic findings suggest that measures of body fat distribution predict health outcomes independent of the overall body fat assessed by body mass index (BMI). This study aimed to evaluate the associations of overall and regional body fat with the severity of hepatic steatosis and fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease. Methods: Bioelectric impedance analysis and two newly developed anthropometric indices, namely, A Body Shape Index (ABSI) and Body Roundness Index (BRI), were used to estimate the body fat. Based on fibroscan parameters, significant hepatic fibrosis and severe steatosis were defined as ≥F2 and >66%, respectively. Results: Higher total body fat (odds ratio [OR] 1.107, 95% confidence intervals (CI) 1.038-1.182, p = 0.002), trunk fat (OR 1.136, 95% CI 1.034-1.248, p = 0.008) and leg fat (OR 1.381, 95% CI 1.139-1.674, p = 0.001) were associated with liver fibrosis. However, in contrast to the total body fat (OR 1.088, 95% CI 1.017-1.164, p = 0.014) and leg fat (OR 1.317, 95% CI 1.066-1.628, p = 0.011), the trunk fat was not associated with severe hepatic steatosis. BRI performed better than trunk, leg and total body fat in predicting hepatic steatosis (OR 2.186, 95% CI 1.370-3.487, p = 0.001) and fibrosis (OR 2.132, 95% CI 1.419-3.204, p < 0.001). Moreover, the trunk to leg fat ratio and ABSI were not independent predictors of either steatosis or fibrosis (p > 0.05). Conclusion: BRI revealed a superior predictive ability for identifying the degree of hepatic steatosis and stiffness than other obesity indices. Additionally, higher levels of adiposity in the trunk, legs, and overall body were linked to an increased risk of developing liver fibrosis. Although trunk fat did not show an association with severe hepatic steatosis, an increase in leg and total fat was related to liver steatosis.

Neuropsychiatric manifestations due to anticholinergic agents and anabolic steroids ingestion: A case series and literature review.

Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The neuropsychiatric effects of anticholinergic agents and anabolic steroids (ASs) can manifest as symptoms like anxiety, agitation, dysarthria, confusion, seizures, visual hallucinations, bizarre behavior, delirium, psychosis, and coma. When dealing with a conscious patient who has ingested an anticholinergic substance, a detailed history of ingestion can aid clinicians in making an accurate diagnosis. However, the lack of information about the substances consumed can complicate diagnosis. In cases where the exposure is unknown, clinicians should consider anticholinergic poisoning in patients showing signs of altered mental status and physical examination findings consistent with anticholinergic toxicity. We report four cases presenting a range of symptoms, including neuropsychiatric manifestations, following the ingestion of the same bodybuilding powders with anticholinergic properties. All four patients consumed yellow and white powders at the same time and in the same place. Laboratory analysis revealed that yellow powder and white powder contained ASs and cyproheptadine, respectively.

Don't Ask Us to Stop Cycling: A Surgical Perspective.

MINI ABSTRACT: In this surgical perspective, we argue that counseling avoidance of bicycle commuting is not the right approach to cycling injury prevention or to overall urban health. Instead, we propose surgeons should take a more holistic approach that includes mitigating individual risk factors as well as creating an equitable environment of safety.

Why Should the FDA Focus on Pragmatic Clinical Research?

This Viewpoint from the FDA discusses how pragmatic clinical research­assessment that uses real-world data, often in combination with research data, after initial marketing approval­can help in evaluation of new technologies, benefit research sites in underresourced settings, and better inform regulatory decisions and clinical practice.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in coronary artery disease and its correlation with inflammatory markers.

Introduction: Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) is an adipokine that is involved in regulation of glucose and lipid metabolism, inflammation, and insulin sensitivity. However, the exact role of CTRP6 in metabolic processes remains unclear due to conflicting findings. To address current gap, we aimed to investigate the serum levels of CTRP6 in patients with coronary artery disease (CAD) and its association with inflammatory cytokines. Method: In this case-control study, the serum levels of CTRP6, interlukin-6 (IL-6), tumor necrosis factor- α (TNF-α), adiponectin, and fasting insulin were measured using enzyme-linked immunosorbent assay (ELISA) kits in a total of 176 participants, consisting of 88 CAD patients and 88 control subjects. Additionally, various anthropometric and biochemical measurements were measured and compared between cases and controls. Results: The present study found that serum levels of CTRP6 were significantly higher in the CAD group (561.3 ± 15.14) compared to the control group (429.3 ± 12.85, p < 0.001). After adjusting for age, sex, and body mass index (BMI), CTRP6 levels were found to be positively associated with the risk of CAD (p < 0.001). Correlation analysis in CAD subjects revealed a positive correlation between CTRP6 levels and BMI, systolic blood pressure (SBP), malondialdehyde (MDA), TNF-α, and IL-6, as well as a negative correlation with creatinine and total anti-oxidant capacity. Conclusion: The findings of this study provide novel evidence that elevated serum levels of CTRP6 are significantly associated with an increased risk of developing CAD. Moreover, our results indicate a correlation between CTRP6 and various risk factors for atherosclerosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01415-5.

Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants. Our gene-level collapsing analysis revealed that rare damaging variants in SAMHD1 as well as genes in the DNA damage response pathway (BRCA2, ATM and CHEK2) are associated with the risk of overall prostate cancer. We also found that rare damaging variants in AOX1 and BRCA2 were associated with increased severity of prostate cancer in a case-only analysis of aggressive versus non-aggressive prostate cancer. At the single-variant level, we found rare non-synonymous variants in three genes (HOXB13, CHEK2, BIK) significantly associated with increased risk of overall prostate cancer and in four genes (ANO7, SPDL1, AR, TERT) with decreased risk. Altogether, this study provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity.

Lower-extremity inter-joint coordination variability in active individuals with transtibial amputation and healthy males during gait.

This study was aimed to compare the variability of inter-joint coordination in the lower-extremities during gait between active individuals with transtibial amputation (TTAs) and healthy individuals (HIs). Fifteen active male TTAs (age: 40.6 ± 16.24 years, height: 1.74 ± 0.09 m, and mass: 71.2 ± 8.87 kg) and HIs (age: 37.25 ± 13.11 years, height: 1.75 ± 0.06 m, and mass: 74 ± 8.75 kg) without gait disabilities voluntarily participated in the study. Participants walked along a level walkway covered with Vicon motion capture system, and their lower-extremity kinematics data were recorded during gait. The spatiotemporal gait parameters, lower-extremity joint range of motion (ROM), and their coordination and variability were calculated and averaged to report a single value for each parameter based on biomechanical symmetry assumption in the lower limbs of HIs. Additionally, these parameters were separately calculated and reported for the intact limb (IL) and the prosthesis limb (PL) in TTAs individuals. Finally, a comparison was made between the averaged values in HIs and those in the IL and PL of TTAs subjects. The results showed that the IL had a significantly lower stride length than that of the PL and averaged value in HIs, and the IL had a significantly lower knee ROM and greater stance-phase duration than that of HIs. Moreover, TTAs showed different coordination patterns in pelvis-to-hip, hip-to-knee, and hip-to-ankle couplings in some parts of the gait cycle. It concludes that the active TTAs with PLs walked with more flexion of the knee and hip, which may indicate a progressive walking strategy and the differences in coordination patterns suggest active TTA individuals used different neuromuscular control strategies to adapt to their amputation. Researchers can extend this work by investigating variations in these parameters across diverse patient populations, including different amputation etiologies and prosthetic designs. Moreover, Clinicians can use the findings to tailor rehabilitation programs for TTAs, emphasizing joint flexibility and coordination.

Potential Association Between Latent Toxoplasma gondii Infection and Suicide Attempts: A Case-Control Registry-Based Study.

Toxoplasma gondii is a ubiquitous parasitic protozoan that may be an important cause of neurological and psychiatric diseases. The purpose of this case-control registry-based study was to evaluate the prevalence of T. gondii infection and related risk factors among subjects who attempted suicide by drug use and a control group at the Iranian National Registry Center for Toxoplasmosis in Mazandaran Province, northern Iran. Baseline data were collected from participants using a questionnaire, and a blood sample was taken from each individual. The plasma was prepared for serological analysis, whereas the buffy coat was used for molecular analysis. Out of 282 individuals (147 cases with suicide attempters [SA] and 135 controls), 42.9% of patients and 16.3% of control subjects were positive for anti-Toxoplasma immunoglobin G (IgG), but all participants were negative for T. gondii DNA and anti-Toxoplasma immunoglobin M. Based on multiple logistic regressions, IgG seropositivity in SA in the age group of 20-30 years was 3.22 times higher than that in the control group (p < 0.001). These findings suggest that latent T. gondii infection among SA is significantly higher than that in healthy individuals, indicating a potential association between latent toxoplasmosis and SA at least in the studied area. Further research is needed to shed light on the potential association between T. gondii and suicide among different populations and areas of the world.

Genotypic Frequency of Rh Cw Antigen in Blood Donors of Northern Pakistan.

OBJECTIVE: To determine the genotypic frequency of Rh Cw antigen in blood donors of Northern Pakistan. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the Study: Department of Molecular Haematology, Armed Forces Institute of Transfusion (AFIT), Rawalpindi, Pakistan, from August 2022 to January 2023. METHODOLOGY: Blood donors were randomly selected. Venous blood samples were taken in K3-EDTA anticoagulant tubes. ABO and Rh D grouping were performed conventionally. DNA for Rh Cw genotyping was extracted via Chelex TM, followed by PCR amplification using an ABI 2700 thermal cycler. Human growth hormone (HGH) acts as an internal control. Amplified products underwent Polyacrylamide gel Electrophoresis (PAGE). RESULTS: There were 400 randomly chosen donors whose ages ranged from 26-35 years, with a predominantly male population (94.8%) of Punjabi origin (67.8%). The majority (87.3%) was RhD positive. Blood group B was the most prevalent (35%) in the studied population, followed by O (34.75%). Only 1.5% had Rh Cw antigen. Rh Cw was more prevalent in ABO-positive participants (87.25%) compared to ABO-negative (12.75%). CONCLUSION: There was a 1.5% prevalence of Rh Cw antigen genotype in randomly selected Northern Pakistani blood donors. Rh Cw prevalence was higher in ABO-positive participants. Significant correlation (<0.05) existed between RhD and Cw antigens. Given the implications of anti-Cw antibody, including Cw antigen-positive cells in antibody screening is recommended. KEY WORDS: Alloimmunisation, Blood donors, HDFN, Phenotype, Rh antigens, Transfusion.

Relationship between academic procrastination, self-esteem, and moral intelligence among medical sciences students: a cross-sectional study.

BACKGROUND: Academic procrastination is a widespread phenomenon among students. Therefore, evaluating the related factors has always been among the major concerns of educational system researchers. The present study aimed to determine the relationship of academic procrastination with self-esteem and moral intelligence in Shahroud University of Medical Sciences students. METHODS: This cross-sectional descriptive-analytical study was conducted on 205 medical sciences students. Participants were selected based on inclusion and exclusion criteria using the convenience sampling technique. The data collection tools included a demographic information form, Solomon and Rothblum's Procrastination Assessment Scale-Students, Rosenberg Self-Esteem Scale, and Lennick and Kiel's Moral Intelligence Questionnaire, all of which were completed online. The data were analyzed using descriptive statistics and inferential tests (multivariate linear regression with backward method) in SPSS software. RESULTS: 96.1% of participating students experienced moderate to severe levels of academic procrastination. Based on the results of the backward multivariate linear regression model, the variables in the model explained 27.7% of the variance of academic procrastination. Additionally, self-esteem (P < 0.001, ß=-0.942), grade point average (P < 0.001, ß=-2.383), and interest in the study field (P = 0.006, ß=-1.139) were reported as factors related to students' academic procrastination. CONCLUSION: According to the findings of this study, the majority of students suffer from high levels of academic procrastination. Furthermore, this problem was associated with low levels of self-esteem, grade point average, and interest in their field of study.

Relationship between resilience and self-efficacy among Iranian nurses: a cross-sectional study during the post-Corona era.

BACKGROUND: Resilience and self-efficacy play an influential role in nurses' clinical performance, which are considered resources for improving adaptability and promoting work engagement. This study aimed to determine the relationship between resilience and self-efficacy among nurses at Shahroud University of Medical Sciences hospitals during the post-Corona era. METHODS: This cross-sectional study was conducted on 280 nurses in all clinical departments. Nurses with a bachelor of science in nursing or higher degree and at least one year of full-time work experience were included in the study using a convenience sampling method. Participants completed a three-part tool, which included the demographic information form, the Connor-Davidson Resilience Scale, and the General Self-Efficacy Scale. The data were analyzed using descriptive statistics and inferential tests (multivariate linear regression using the backward method). RESULTS: In this study, nurses reported low levels of resilience (63.64 ± 15.66) and high levels of self-efficacy (63.01 ± 9.57). Among the five resilience subscales, the highest mean item score was associated with "spiritual influences" (2.80 out of 4), while the lowest mean item score was associated with "trust in one's instincts and tolerance of negative affect" (2.36 out of 4). Furthermore, the multivariate linear regression model results indicated that self-efficacy accounted for 33.6% of the variance in resilience (P < 0.001 and ß = 0.952). CONCLUSION: According to the results of the present study, it is suggested that nurses' psychological capabilities, such as self-efficacy, should be increased to improve resilience and address the stressful conditions of the work environment.

Health Literacy Among University Students in the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: The purpose of this systematic review was to assess different studies that worked on university students' health literacy during covid19 pandemic and to make an overview of this issue to recognize possible determinants associated with health literacy. METHODS: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Four databases (Google Scholar, Web of Science, Pubmed, and Scopus) were used for searching cross-sectional works that assessed the health literacy of university students. We searched papers from December 1st, 2019 up to June 10th, 2022. English language articles were used. Studies were done in countries including; Iran, Pakistan, the USA, Vietnam, China, Colombia, Germany, and Indonesia. RESULTS: The systematic review contains 12 research studies involving 17773 students. There was a relationship between health literacy and some determinants. Positive determinants included age, female gender, Urban background, cognitive maturity, Higher educational qualification, information source (Health workers), number of semesters, and parental education. Some negative determinants were male gender, Rural background, smoking, drinking, being able to pay for medication, lower conspiracy beliefs, and higher fear of COVID-19. CONCLUSION: University students around the world should have courses about health literacy according to university disciplines. These courses should be available for students of different fields to enhance their effectiveness, and training should be associated with students' needs and their subgroup traits.

Vision-related quality of life in patients with retinal vein occlusion.

PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.

Precision Oncology in Breast Cancer Surgery.

Outcomes for patients with breast cancer have improved over time due to increased screening and the availability of more effective therapies. It is important to recognize that breast cancer is a heterogeneous disease that requires treatment based on molecular characteristics. Early endpoints such as pathologic complete response correlate with event-free survival, allowing the opportunity to consider de-escalation of certain cancer treatments to avoid overtreatment. This article discusses clinical trials of tailoring treatment (eg, I-SPY2) and screening (eg, WISDOM) to individual patients based on their unique risk features.

The Effects of Coenzyme Q10 on Contrast-Induced Acute Kidney Injury in Type 2 Diabetes: A Randomized Clinical Trial.

Contrast-induced acute kidney injury (CI-AKI) is a frequent challenge following the injection of contrast media and its subsequent oxidative stress. The aim of the present study was to evaluate the preventive effects of coenzyme Q10 (Q10), as a mitochondrial-targeted antioxidant in CI-AKI in diabetic patients, who account for a large proportion of angiographic cases. A total of 118 diabetic patients were randomly assigned to receive 120 mg of oral coenzyme Q10 (Q10 group) or placebo (Placebo group) for four days, starting 24 hours before contrast media injection. Blood urea nitrogen (BUN), serum and urinary creatinine, estimated glomerular filtration rate (eGFR), urinary malondialdehyde (UMDA), urinary total antioxidant capacity (UTAC), and urinary mitochondrial to nuclearDNA ratios (mtDNA/nDNA ratio) were evaluated before and after the treatment period. Urine sediments were also evaluated to report the urine microscopy score (UMS).The levels of BUN, serum and urine creatinine, and UMS were similar in the Q10 and placebo groups. EGFR was lower in the Q10 group before the treatment (p=0.013) but not after. The urinary mtDNA/nDNA ratio was 3.05±1.68 and 3.69±2.58 in placebo and Q10 groups, but UTAC was found to be lower in Q10 both before (p=0.006) and after the treatment (p<0.001). The incidence of CI-AKI was 14.40% and the mtDNA/nNDA ratio was similar between CI-AKI and non-CI-AKI patients. In conclusion, Q10 treatment shows no favorable effect on prevention of CI-AKI or a urinary mtDNA/nDNA ratio among diabetic patients.

The effect of spiritual reminiscence therapy on depression and hope among Iranian older adults: a quasi-experimental study.

This quasi-experimental study aimed to evaluate the impact of spiritual reminiscence therapy (SRT) on depression and hope among older adults living in Shahroud, northeast of Iran. One hundred fifty-six older adults were selected through convenience sampling and assigned non-randomly to the intervention (n= 78) and control (n= 78) groups. The data collection tools included the Geriatric Depression Scale and Adult Hope Scale. For the intervention group, SRT was conducted in six weekly sessions, each lasting 60 to 90 min, over six weeks. The data were analyzed utilizing descriptive statistics and inferential tests (independent t-test, Chi-square test, and analysis of covariance). The two groups' post-intervention mean scores on depression (t= 11.63 and P< 0.001), and hope (t= 4.41 and P< 0.001) were statistically different, suggesting that SRT positively affected older adults by alleviating despair and boosting hope. The findings indicate that engaging in SRT can be beneficial in reducing depression and fostering hope among older adults.

Mini review: human clinical studies of stem cell therapy in keratoconus.

Treatment of keratoconus is one of the most interesting research fields for researchers in the world. Regenerative medicine based on human stem cells in the treatment of keratoconus has recently received attention. Despite extensive laboratory and animal studies in regenerative medicine of cornea, there are limited clinical studies in keratoconus. These studies showed promising results of stem cell therapy. In initial studies, the transplantation of these cells into stroma was associated with increased vision and improved corneal parameters without side effects. In this article, we tried to review different aspects of keratoconus stem cell therapy, including cell extraction and culture, surgical procedure, effectiveness and safety of this method in human clinical studies.