Journal of Drug Assessment最新文献

Background: Cardiogenic shock (CS) is an acute complex condition leading to morbidity and mortality. Vasoactive medications, such as vasopressors and inotropes are considered the cornerstone of pharmacological treatment of CS to improve end-organ perfusion by increasing cardiac output (CO) and blood pressure (BP), thus preventing multiorgan failure.

Objective: A critical review was conducted to analyze the currently available randomized studies of vasoactive agents in CS to determine the indications of each agent and to critically appraise the methodological quality of the studies.

Methods: PubMed database search was conducted to identify randomized controlled trials (RCTs) on vasoactive therapy in CS. After study selection, the internal validity of the selected studies was critically appraised using the three-item Jadad scale.

Results: Nine studies randomized 2388 patients with a mean age ranged between 62 and 69 years, were identified. Seven of studies investigated CS in the setting of acute myocardial infarction (AMI). The studies evaluated the comparisons of norepinephrine (NE) vs. dopamine, epinephrine vs. NE, levosimendan vs. dobutamine, enoximone or placebo, and nitric oxide synthase inhibitors (NOSi) vs. placebo. The mean Jadad score of the nine studies was 3.33, with only three studies of a score of 5.

Conclusions: The evidence from the studies of vasoactive agents in CS carries uncertainties. The methodological quality between the studies is variable due to the inherent difficulties to conduct a study in CS. Vasopressors and inotropes continue to have a fundamental role given the lack of pharmacological alternatives.

Background: There have been significant advances in Cystic Fibrosis (CF) treatment, with the introduction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators. Adherence is an important goal for CF management, as nonadherence is linked to poor health outcomes.

Objective: To calculate the medication adherence in patients taking CFTR modulators using a national specialty pharmacy database.

Methods: This retrospective observational cohort study utilized de-identified specialty pharmacy data from September 2017 to August 2018 to assess medication adherence for three CFTR modulators: ivacaftor, lumacaftor/ivacaftor, and tezacaftor/ivacaftor & ivacaftor. The primary outcome was proportion of days covered (PDC) for each medication, with mean PDC values compared across age groups and insurance characteristics. All analyses were performed using the SAS 9.4 University Edition (SAS Institute, Cary, NC).

Results: A total of 2,548 patients were analyzed, including 1,289 (50.59%) patients on lumacaftor/ivacaftor, 784 (30.77%) on ivacaftor, and 475 (18.64%) on tezacaftor/ivacaftor & ivacaftor. The mean PDC value for all CFTR modulators was above 0.80. Tezacaftor/ivacaftor & ivacaftor had the highest overall PDC of 0.92, while PDC values for both lumacaftor/ivacaftor and ivacaftor were 0.84. Children/adolescents on lumacaftor/ivacaftor (p = 0.0001) and tezacaftor/ivacaftor & ivacaftor (p = 0.001) had significantly higher mean PDC values compared to adults but not for ivacaftor (p = 0.3744). No statistical differences were seen in PDC across insurance characteristics.

Conclusion: To the best of our knowledge, this is the first study to assess the adherence of three CFTR modulators using a large nationwide specialty database. With high acquisition costs of CFTR modulator therapies, there is a need to improve rates of adherence in patients with CF.

Purpose: To report the clinical course of a woman treated with intravitreal bevacizumab during pregnancy.

Case report: A 27-year-old female with poorly controlled diabetes and a history of two previous miscarriage was referred to our hospital with sudden deterioration in visual acuity (VA) in her right eye. Ocular findings revealed severe Proliferative Diabetic Retinopathy (PDR) complicated with preretinal hemorrhages in her right eye, and after maximal Panretinal Photocoagulation (PRP) bilaterally, she was treated with intravitreal injection of bevacizumab (IVB) into the right eye. Twenty four hours after the bevacizumab injection, she reported vaginal bleeding, and ultrasound confirmed a 12-week pregnancy of which the patient was unaware. The patient suffered from pregnancy loss.

Conclusion: Use of intravitreal anti-VEGF by pregnant woman may only be justified if the potential benefit outweighs the potential risk to the fetus and only if clearly needed. Intravitreal bevacizumab during pregnancy in women with a history of miscarriage should be used with caution.

Background: H. pylori infection is associated with both benign and malignant gastrointestinal diseases. However, no studies have been conducted locally describing the prevalence of H. pylori and its associated GIT diseases. The objectives of this study are to determine the prevalence of H. pylori, and the incidence of PUD and gastric malignancies among patients who are infected with H. pylori or who have the stigmata of previous exposure to H. pylori.

Material and methods: Data was collected retrospectively from files of adult patients with upper gastro-intestinal symptoms from January to December, 2012. The gastric mucosal biopsy specimens were analyzed for the presence of H. pylori, chronic gastritis, PUD, and gastric malignancies.

Results: Of 156 records there were 70 (45%) males and 86 (55%) females, with a median age of 56.5. The prevalence of H. pylori was 54.5%; 95% of 156 had chronic gastritis (CG). Ninety-sever percent of the 85 H. pylori positive and 93% of the 71 H. pylori negative patients had CG. However, the difference was not statistically significant (97% vs 93%, p = 0.322). The incidence of PUD was 16% and 10 (6.4%) had gastric malignancies, of which four (2.7%) and three (2%) were antral intestinal-type and proximal diffuse types, respectively. Three (2%) had gastric MALT lymphoma. The risk of both gastric malignancies and PUD was demonstrated to increase with advancing age.

Discussion and conclusion: The prevalence of H. pylori was equivalent to the global prevalence; however, high prevalence of CG may be indicative of high local infection rate. The incidence of H. pylori and/or chronic gastritis-associated intestinal-type gastric adenocarcinoma, MALT lymphoma, and PUD is equivalent to that reported globally. Advancing age and active H. pylori infection or stigmata of past exposure thereto are associated with increased risk of peptic ulcers and malignant gastric diseases.

Objective: To explore treatment preferences of patients with Hereditary Angioedema (HAE), a debilitating disorder characterized by potentially life-threatening, recurrent episodes of swelling, resulting in significant physical, emotional, and economic burden. With newer oral prophylactic treatments on the horizon, it is important to understand patients' preferences.

Methods: An online survey was conducted in 2018 among United States (US) adult patients diagnosed with Type I or II HAE. Respondents were recruited anonymously from online panels and social media.

Results: Online surveys were completed by 75 patients diagnosed with HAE by a healthcare provider, with a mean of 16.7 years since diagnosis. Most patients (64%) report taking at least one medication for prophylaxis of HAE attacks. While almost all patients surveyed agree it is important to take preventative medication as prescribed, over half (52%) of patients report HAE prophylactic treatment to be burdensome. Despite stating that they like their current medications, 98% of the prophylactic HAE medication users would prefer an oral treatment if available; almost all (96%) prophylaxis users agree that oral preventative medication would fit their life better than an injectable medication, with 67% of users citing convenience as the primary reason to try an oral preventative HAE medication. If a more convenient option were available, nearly all (96%) patients currently not treating their HAE prophylactically would feel encouraged to do so.

Conclusions: Most patients with HAE would prefer a newer generation oral prophylactic medication that would decrease treatment burden and allow them to live fuller lives.

Purpose: Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients.

Design: This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies.

Results: PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations.

Conclusions: Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

Objective: Hyperhidrosis (excessive sweating) is associated with significant quality-of-life burden yet is often undertreated. With limited FDA-approved treatments, health care providers must determine optimal treatment among approved and off-label options. Key objectives of this review were to reassess, update, and expand a previous systematic review of commonly used treatment options for primary hyperhidrosis, including consideration of aluminum and zirconium compounds.

Methods: We performed a qualitative systematic review of efficacy, health-related quality of life, satisfaction, and safety of interventions, replicating and expanding the strategy outlined in a previous systematic review, with the addition of studies utilizing a within-patient design. We performed a critical appraisal of identified studies to determine risk of bias (RoB) and strength of evidence (SOE).

Results: A total of 32 studies were eligible for critical appraisal. Only three studies - two clinical trials of glycopyrronium cloth (2.4%) and one trial of botulinum toxin A injections in axillary hyperhidrosis were rated as "low" RoB; both had SOE ratings of "moderate" for use in axillary hyperhidrosis - the highest rating included in this review.

Conclusions: Optimal treatment choice depends on several factors, including understanding the quality of evidence regarding each treatment's efficacy and safety (considerations of convenience and cost are beyond the scope of this review). In hyperhidrosis, as in other clinical conditions, treatment decisions should be patient centered. At this time, because of the quality of evidence, only imprecise estimates of effect are possible for hyperhidrosis treatments included in this review, and statements about comparative effectiveness are not possible.

Objective: The purpose of this study is to review CDK 4/6 inhibitors used to treat metastatic breast cancer for patient safety, cost and utilization. By evaluating patient outcomes and payer influence, this study will provide critical information to aid prescribers in therapeutic decisions.

Methods: This retrospective cohort study included patients from a national specialty pharmacy with a diagnosis of breast cancer and received either palbociclib, abemaciclib, or ribociclib for treatment. Patients were stratified into four subgroups based on their total oncolytic regimen at the time of their first eligible study medication dispense. Pharmacy claims data were reviewed to determine cost and therapy adherence.

Results: The mean proportion of days covered was highest in patients on combination therapy with a hormone agent, 81.0%. While secondary insurances largely affected final patient out-of-pocket costs, final copays were significantly lower than the average wholesale price (AWP) of each CDK 4/6 inhibitor. When analyzing patient reported side effects, over 60% of the study population did not experience an adverse drug event (ADE) during the study time period. Ribociclib had the fewest number of reported side effects with abemaciclib patients reporting the most. Although reported ADE profiles were similar across all three study medications, difference in frequency should be evaluated when considering medication choice with specific comorbidities.

Conclusion: CDK 4/6 inhibitors have demonstrated safety and tolerability in HR-positive/HER2-negative breast cancer patients. Real world safety data and out-of-pocket patient costs in addition patient specific comorbidities should be considered when developing a treatment plan that includes a CDK 4/6 inhibitor selection.

Aims: The ability of a patient to receive anti-cancer treatment depends on a variety of factors, including performance status (PS), which is typically measured using the Eastern Cooperative Oncology Group (ECOG) scale. This study hypothesized that there would be a strong and positive correlation between ECOG PS values and healthcare resource utilization (HCRU) and a strong and negative correlation with the use of anti-cancer therapy.

Materials and methods: Patients with colorectal, lung or gastric cancer were included in this retrospective analysis of administrative claims data linked to electronic medical records (EMR). All-cause HCRU (hospitalization/inpatient care, emergency room visits, systemic anti-cancer therapy, radiation therapy, outpatient physician visits, hospice, home health care and key supportive care treatments such as anti-emetics, hematopoietic treatments, transfusions, and durable medical equipment) was evaluated by baseline ECOG PS value and PS over time. Adjusted multivariable regression analysis was used to assess the relationship between baseline ECOG PS and HCRU. Regression analyses were conducted to explore the relationship between other baseline variables and HCRU.

Results: There were 1311 patients included in this study. There was low correlation between PS and any HCRU variable or receipt of anti-cancer therapy (correlation coefficients all <0.10). In regression analyses, the proportion of patients with poor PS (PS = 2+) who were hospitalized was not significantly different from those with good PS (PS = 0/1) (28.9% versus 19.3%, p = .07).

Limitations: The low rate of reporting of PS and the small sample size of patient groups in this study.

Conclusions: There is very little evidence of a relationship between ECOG PS and HCRU, ECOG PS, or anti-cancer therapy in this study, in part due to low rates of and lack of variability in reported PS. There is some evidence that baseline comorbidities were significantly associated with HCRU and should be accounted for in future research evaluating HCRU.

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in humans and the mainstay of treatment is anticoagulation unless contraindicated. Non-vitamin K oral anticoagulants have not been duly evaluated in randomized controlled trials in CVT.

Objective: To compare the efficacy and safety of oral rivaroxaban with vitamin K anticoagulant (warfarin) in preventing recurrent venous thromboembolism (VTE) in patients with CVT.

Methods: Adult patients with CVT, who were stable after 5-12 days of treatment with parenteral heparin 1 mg/kg, were screened for eligibility. The patients were randomly divided into two groups to receive oral rivaroxaban 20-30 mg daily or warfarin 1, 3 or 5 mg daily (with the dose adjusted to maintain an INR of 2-3), for 3-12 months. Recanalization rates, periprocedural complications, and clinical outcomes were assessed by Magnetic Resonance Venography (MRV) and National Institutes of Health Stroke Scale (NIHSS) at 3rd, 6th and 12th month follow-ups.

Results: In total, 45 patients with CVT were randomized to the two treatment groups (21 to rivaroxaban and 24 to warfarin). Overall recanalization was achieved by 18 (86%) and 20 (83%) cases from rivaroxaban and warfarin group, respectively at 6th month follow-up; and by all 45 (100%) cases from the both groups at 12th month follow-up. Excellent outcome (NIHSS score 0) was obtained by 20 (95%) cases from rivaroxaban group at 3rd to 12th month follow-ups; and by 23 (96%) cases at 6th to 12th month follow-ups. There were no major bleeding events during the trial. None of the patients developed recurrence of thrombosis. Statistically, no significant difference between the two treatment groups in terms of recanalization and clinical outcomes could be observed.

Conclusion: Rivaroxaban is a safe option in CVT however; larger randomized controlled studies will impact the results validity.