Abstract Background Antiretroviral therapy (ART) is highly effective in people living with HIV (PLHIV), but its success depends on treatment satisfaction and adherence. A determinant of satisfaction regards how the medication is delivered to the patient, namely how it is contained (e.g., bottles, blisters, etc). A new packaging of Biktarvy ® has been introduced as a monthly blister, aiming to improve satisfaction, facilitate traceability of daily medication, portability, and discretion (reducing stigma associated with ART), and, ultimately, enhance adherence. Goals The study’s objective was to assess the impact of changing the packaging of Biktarvy® (B/F/TAF) from a standard pill bottle to a monthly blister with a weekly calendar on therapy satisfaction. Additionally, the association between treatment satisfaction and selected patients’ characteristics (e.g., ART duration) was evaluated. A secondary goal was to characterize the association between the change of packaging on patient’s adherence. Methods This is an observational longitudinal (retrospective and prospective) study with patients following ART for at least six months (ambulatory clinical management) recruited according to a non-probabilistic sequential sampling. Satisfaction was measured at two different moments: at baseline, HIVTSQs were used to assess satisfaction within the previous six months’ use of medication containers (bottles). Six months later, patients filled in the HIVTSQc to assess their perception of satisfaction change with the new packaging (blister). Adherence was assessed by pharmacy medication dispensing at the hospital. Results The study enrolled 105 patients in two selected centers (102 patients completed the study). Patients were significantly more satisfied (HIVTSQc scores) with ART when using the new Biktarvy® blister pack package. Importantly, gains of ART satisfaction were higher among those less satisfied with the bottle packaging. No significant associations were found between HIVTSQc scores and sociodemographic or ART-related variables.
Essential hypertension (EH) is a disease in which both environment and genes have an important role. This study was designed to identify the interaction model between genetic variants and environmental risk factors that most highly potentiates EH development.We performed a case-control study with 1641 participants (mean age 50.6 ± 8.1 years), specifically 848 patients with EH and 793 controls, adjusted for gender and age. Traditional risk factors, biochemical and genetic parameters, including the genotypic discrimination of 14 genetic variants previously associated with EH, were investigated. Multifactorial dimensionality reduction (MDR) software was used to analyze gene-environment interactions. Validation was performed using logistic regression analysis with environmental risk factors, significant genetic variants, and the best MDR model.The best model indicates that the interactions among the ADD1 rs4961 640T allele, diabetes, and obesity (body mass index ≥30) increase approximately four-fold the risk of EH (odds ratio = 3.725; 95% confidence interval: 2.945-4.711; p < 0.0001).This work showed that the interaction between the ADD1 rs4961 variant, obesity, and the presence of diabetes increased the susceptibility to EH four-fold. In these circumstances, lifestyle adjustment and diabetes control should be intensified in patients who carry the ADD1 variant.
Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10–15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part 1, presented in this manuscript) and the long-term phase (Part 2, presented in a separate manuscript) of IMD. This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers. A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants' experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers' reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase. IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part 1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. Invasive meningococcal disease (IMD) is an uncommon but serious infection. Even with treatment, IMD is deadly for up to 10–15% of people who get sick, and survivors may experience short-term and long-term health problems. While IMD can be prevented through vaccination, many people are not vaccinated. We asked 11 survivors and 3 of their caregivers in the USA about their experiences with IMD during the time of their infection and initial recovery (the "short term"). We were particularly interested in the symptoms that survivors experienced, their diagnosis and treatment experiences, and the impact on survivors' and caregivers' quality of life. Most survivors described leading healthy lives before getting sick. Severe skin rash, fever, and unconsciousness were common symptoms when survivors got the infection. Most participants were admitted to the hospital when symptoms started (many through the emergency room). However, not everyone was diagnosed quickly or accurately, and many experienced delays in receiving care. Treatments could be drastic, such as immediate surgery to remove arms or legs. Survivors and caregivers described feeling scared and traumatized, and many experienced challenges with day-to-day activities. Healthcare-related expenses and the inability to attend school or work led to financial challenges for some. The burden of IMD infection and initial recovery is significant. There is a need for increased public disease awareness, targeted education for healthcare providers, and improved access to prevention measures such as vaccination. The long-term effects of IMD infection were also explored in this study, and are presented in another paper [1].
Abstract Background: Genetic risk score can quantify individual’s predisposition to coronary artery disease; however, its usefulness as an independent risk predictor remains inconclusive. Objective: To evaluate the incremental predictive value of a genetic risk score to traditional risk factors associated with coronary disease. Methods: Thirty-three genetic variants previously associated with coronary disease were analyzed in a case-control population with 2,888 individuals. A multiplicative genetic risk score was calculated and then divided into quartiles, with the 1st quartile as the reference class. Coronary risk was determined by logistic regression analysis. Then, a second logistic regression was performed with traditional risk factors and the last quartile of the genetic risk score. Based on this model, two ROC curves were constructed with and without the genetic score and compared by the Delong test. Statistical significance was considered when p values were less than 0.05. Results: The last quartile of the multiplicative genetic risk score revealed a significant increase in coronary artery disease risk (OR = 2.588; 95% CI: 2.090-3.204; p < 0.0001). The ROC curve based on traditional risk factors estimated an AUC of 0.72, which increased to 0.74 when the genetic risk score was added, revealing a better fit of the model (p < 0.0001). Conclusions: In conclusion, a multilocus genetic risk score was associated with an increased risk for coronary disease in our population. The usual model of traditional risk factors can be improved by incorporating genetic data.
Abstract Coronary Artery Disease (CAD) shares environmental and genetic factors. Young patients with acute coronary syndrome (ACS) carry a poor long-term prognosis. The clinical utility of genetic information in predicting CAD events remains unknown. Aim Evaluate the clinical utility of a multiplicative Genetic Risk Score (mGRS) to predict lifelong residual risk in CAD patients below 55 years with few risk factors. Methods 475 non-diabetic patients with LDL cholesterol levels below 100mg/dL at the first admission who suffered a prior MI at age ≤55 years were followed prospectively for a mean of 5.6±5.3 years. A mGRS was performed with nine variants associated with CAD but not with traditional risk factors (TRF): CDKN2B-AS1 (rs1333049 and rs4977574), TCF21 (rs12190287), PHACTR1 (rs1332844), MIA3 (rs17465637), ADAMTS7 (rs3825807), ZC3HC1 (rs11556924), SMAD3 (rs17228212) and GJA4 (rs618675). The mGRS was subdivided into terciles. Using Cox regression analysis, the predictive and discriminative score ability for events was evaluated. C-statistic discriminated cardiovascular events occurrence. Whether mGRS was included in the TRF model, Net Reclassification Improvement (NRI), or Integrated Discrimination Improvement (IDI) reclassified patients. Kaplan-Meier method estimated survival curves. Results There were 153 patients with at least one cardiovascular event. The bivariate analysis showed the strongest correlation with second and third mGRS tercile, multivessel disease, left ventricular dysfunction, and inflammation. Multivariate Cox regression HR adjusted for events was 1.44 (p=0.103) for the intermediate and 2.00 (p=0.001) for the high-risk tercile. The mGRS inclusion improved C-statistic (∆C-index=0.010; p=0.004), NRI (35.4%; p<0.0001) and IDI (2.7%; p=0.0005). Conclusions Our 9-SNP mGRS better identified and reclassified younger CAD patients with a high probability of cardiovascular events, improving clinical decision-making and reducing costs for therapeutic strategies.
Abstract Background It is known that a low HDL-c level is associated with a high risk of overall mortality. Consequently, it was presumed that achieving higher levels of high-density lipoprotein cholesterol (HDL-c) would reduce the risk or even extend the lifespan. However, clinical trials with medical intervention failed to find clinical benefits. Aim We aimed to investigate the association between (HDL-c) levels and overall mortality using a prospective cohort from Portugal. Methods A prospective sub-study (2001-2022) was performed in a cohort of 1718 participants without coronary artery disease (CAD) of the control arm of the ongoing GENEMACOR study. The participants <65 years were followed during a mean follow-up of 7.0±5.7 years. All demographic, biochemical, and clinical data were collected. Participants were stratified into six levels of HDL-c. Kaplan-Meier estimated differences in the survival probability of each HDL-c level. Cox proportional analysis models (unadjusted and adjusted) were used to assess the association between HDL-c levels and overall mortality. Results The HDL-c levels with the lowest overall mortality rate were 60 to 70 mg/dl, set as the reference level. Total HDL-c strata were associated with overall mortality with a U-shaped relationship: in the control group, the first level (<40 mg/dl) was independently associated with increased risk of overall mortality (HR of 3.533; 95% CI: 1.738-7.178; p<0.0001). This risk drops and falls to the reference level (the lower risk) and rises again to an HR of 3.875 (95% CI: 1.472-10.201; p=0.006) in the very high HDL-c levels (≥80 mg/dl). Conclusions Our results, based on a large Portuguese cohort, suggest that very high HDL-c levels in the normal population may not represent a good prognosis, especially in women. Future research may confirm these findings and investigate the underlying mechanisms.
Abstract Background: Genetic risk score can quantify individual’s predisposition to coronary artery disease; however, its usefulness as an independent risk predictor remains inconclusive. Objective: To evaluate the incremental predictive value of a genetic risk score to traditional risk factors associated with coronary disease. Methods: Thirty-three genetic variants previously associated with coronary disease were analyzed in a case-control population with 2,888 individuals. A multiplicative genetic risk score was calculated and then divided into quartiles, with the 1st quartile as the reference class. Coronary risk was determined by logistic regression analysis. Then, a second logistic regression was performed with traditional risk factors and the last quartile of the genetic risk score. Based on this model, two ROC curves were constructed with and without the genetic score and compared by the Delong test. Statistical significance was considered when p values were less than 0.05. Results: The last quartile of the multiplicative genetic risk score revealed a significant increase in coronary artery disease risk (OR = 2.588; 95% CI: 2.090-3.204; p < 0.0001). The ROC curve based on traditional risk factors estimated an AUC of 0.72, which increased to 0.74 when the genetic risk score was added, revealing a better fit of the model (p < 0.0001). Conclusions: In conclusion, a multilocus genetic risk score was associated with an increased risk for coronary disease in our population. The usual model of traditional risk factors can be improved by incorporating genetic data.
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