AbbVie (Bahamas)

Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.

Esophageal varices are one of the main complications of liver cirrhosis. Upper gastrointestinal endoscopy is the gold standard for the detection of esophageal varices. Many less invasive methods for screening of varices have been investigated and the most recent Baveno VI guidelines suggest that endoscopy is not necessary in patients with liver stiffness <20 kPa and platelets >150,000/μL. A critical review of the literature was performed concerning non-invasive or minimally invasive methods of screening for esophageal varices. Liver and spleen elastography, imaging methods including computed tomography, magnetic resonance imaging and ultrasound, laboratory tests and capsule endoscopy are discussed. The accuracy of each method, and its advantages and limitations compared to endoscopy are analyzed. There are data to support the Baveno VI guidelines, but there is still a lack of large prospective studies and low specificity has been reported for the liver stiffness and platelet count combination. Spleen elastography has shown promising results, as there are data to support its superiority to liver elastography, but it needs further assessment. Computed tomography has shown high diagnostic accuracy and can be part of the diagnostic work up of cirrhotic patients in the future, including screening for varices.

Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related deaths in the United States, increasing by 2% to 3% annually, with a dismal 5-year survival rate of 18%. The Barcelona Clinic Liver Cancer criteria used to guide treatment considers performance status and assessment of liver function by Child-Pugh score in addition to tumor size and location. Curative therapies for HCC include surgical resection, liver transplantation, and tumor ablation. Patients with unresectable or inoperable lesions should be considered for arterially directed embolic therapy, systemic therapy, or radiation. Options for first-line systemic therapy of advanced HCC include sorafenib, lenvatinib, and atezolizumab plus bevacizumab. Nivolumab may be an option in patients with advanced HCC who are ineligible for tyrosine kinase inhibitors or other anti-angiogenic agents. Options for subsequent therapy following disease progression include regorafenib, cabozantinib, ramucirumab, lenvatinib, nivolumab, nivolumab plus ipilimumab, sorafenib, or pembrolizumab. Patients with advanced HCC are at a high risk of adverse effects because of baseline hepatic dysfunction, comorbidities associated with chronic liver disease, and potential drug-drug interactions. Improved tolerance of therapies for advanced HCC may lead to reduction in treatment discontinuation and contribute to better patient outcomes. Managed care pharmacists should understand the recent efficacy and safety data, guideline recommendations, and treatment algorithms for management of HCC.

OBJECTIVES: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs. METHODS: Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs. RESULTS: Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%) and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role. CONCLUSIONS: In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.

BACKGROUND: Pathogenic variants in filaggrin (FLG) are associated with an increased risk of atopic dermatitis (AD). OBJECTIVE: We evaluated the influence of FLG variants on the effectiveness of dupilumab treatment in AD. METHODS: This prospective observational study included adult AD patients treated with dupilumab from the BioDay registry. FLG was analyzed with single-molecule molecular inversion probe-targeted sequencing. Novel mutations were confirmed by Sanger sequencing. Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), numeric rating scale (NRS) pruritus, Dermatology Quality of Life Index (DLQI), and Patient-Oriented Eczema Measure (POEM) were assessed at baseline and at weeks 16 and 52. The study was registered at ClinicalTrials.gov as NCT03549416. RESULTS: , while differences in delta scores were nonsignificant. CONCLUSION: The effectiveness of dupilumab treatment in AD patients was not influenced by pathogenic FLG variants. However, patients with biallelic pathogenic FLG variants tended to have drier skin before and during dupilumab treatment compared to patients with monoallelic pathogenic variants or wild-type alleles.

Liver cancer is the most rapidly increasing cancer in the United States and is associated with a high cancer-related mortality. Seventy-five percent of liver cancers are hepatocellular carcinoma (HCC) resulting from cirrhosis. Patients are typically diagnosed late in the disease, with a relatively small percentage eligible for curative treatments. Despite the addition of several new therapies for advanced HCC, the 5-year survival rate is just 18%. The direct and indirect costs of HCC are substantial, and are expected to increase with the rise in disease incidence as well as a growing number of high-cost therapies entering the market. There are opportunities to improve the quality of care for patients with HCC through implementation of value-based reimbursement principles and pharmacist involvement in care.

OBJECTIVE: To assess the delivery of advanced specialized medical care using The Partnered Care Model as a means of providing affordable access to all, irrespective of ability to pay. DESIGN AND METHODS: A retrospective analysis of all persons presenting to a specialized, private, cardiac unit, The Bahamas Interventional Cardiology Center (BICC), over an 8.5-year period from March 1996 to September 2004 was conducted. The Bahamas Heart Center's Discounted Service System had been applied since inception to all patients in three groups including insured patients billed at 100% of the fee schedule of The Medical Association of the Bahamas for the procedures performed, private self-pay and government patients billed at 75% and 50% respectively. Their respective distribution and contributions to total revenue was analyzed. A series of financial models were constructed taking into consideration variables that could influence the percentages of revenues collected from each sector and the number of individuals served RESULTS: One thousand five-hundred and forty-two patients received services in BICC over the 8.5 year period (56% males and 44% females age range: 0.25 - 96 years, with mean age of 55.7 years). One thousand eight-hundred and eighty-eight patient-procedures were performed, with 51% insured generating 69% total revenue, 18% Private producing 16% Revenue, and 31% Government patients generating 15%. Financial models were created to predict revenue behaviour in various scenarios. CONCLUSION: Partnered Care is a viable alternative for Governments (Ministries of Health) of developing countries to provide costly specialized healthcare to their populations at minimal expense and capital outlay. Partnered Care reduces the otherwise overwhelming burden of healthcare cost to governments, particularly in developing countries, by sharing the burden of care between the private, user and government sectors.

Three hundred forty-one patients were on lamivudine, 60 were on adefovir, 188 were on entecavir, 467 were on tenofovir, and 32 were on combination therapies. ROC analysis for the predictive values of HCC scores showed that AUROC values were 0.804 for CU-HCC, 0.809 for REACH-B and 0.882 for GAG-HCC. These values were similar in patients without therapy and with entecavir and tenofovir therapies as in the literature. The most predictive GAG-HCC score had sensitivity of 97.3% and negative predictive value of 99.9%. Conclusion: In this large cohort of Caucasian HBV patients, all of these scores had good predictive values for HCC development both in patients on treatment and in patients who did not receive antiviral treatment.

<title>Abstract</title> The introduction of daratumumab has improved the treatment outcomes for multiple myeloma (MM). However, infectious complications such as pneumonia are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases. There are few reports on patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy. CMV infection was defined as CMV antigenemia positivity. Patients who did not undergo CMV antigenemia testing were considered to have no CMV infection. The frequency of CMV infection was calculated as the cumulative incidence rate, considering death during daratumumab administration without CMV infection as a competing event. The median age at treatment initiation was 71 years (range, 50–82 years), and 50.9% of the patients were female. The median duration of daratumumab administration was 10.0 months (range, 0.3–63.8 months). Nine patients developed CMV infection, and the cumulative incidence rate at six months was 18.1% (95% confidence interval: 8.9–30.1%). One patient experienced CMV retinitis and required antiviral therapy, while the remaining eight patients did not require treatment and could be managed through observation. During daratumumab treatment for NDMM, very few cases of CMV infection required treatment. However, the incidence of CMV infection was relatively high, suggesting that regular monitoring of CMV is worth considering for more appropriate management with daratumumab treatment.

Agree (A), Neutral, Disagree (D), Strongly Disagree (SD). * -Hispanic, Asian, Mixed, and Other/Unknown for race, which were grouped and analyzed together. ***Statistical tests were conducted using z-tests in R 4.0.3, with statistical significance determined at a P value <0.05.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence.

This chapter provides an overview of some statistical methods for assessing safety data in a blinded fashion. Broadly speaking, these methods can be subdivided into three broad categories including, frequentist methods, Bayesian methods, and likelihood methods. Bayesian methods make use of prior information and the likelihood leading to a posterior distribution from which inference is made. Whether the statistical method used is frequentist, Bayesian, or likelihood-based, the ultimate objective is to make a decision on the basis of accrued blinded data. In a broad sense, safety monitoring spans from individual trial level to program level, from unblinded to blinded, from expected to unexpected adverse events (AEs), and from patient profiles to aggregate safety monitoring and benefit-risk assessment. Drug development programs can continue for long periods of time, and as such, some safety information on the drug may be known from completed studies.