Background As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV.Objective To better understand the current treatment and comorbidity burden in people living with HIV (PLWH).Methods Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies.Results Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times.Conclusions There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.
A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8-fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed.
Purpose: Discovery of falsified Symbicort 320/9 Turbohaler identified in the UK in 2013 demonstrated that falsified dry powder inhalers were also present in the European market. This work aimed to investigate the current situation of formoterol-containing dry powder inhalers in Europe and North Africa by assessing their aerodynamic performance profile. Methods: A total of eight registered formoterol-based dry powder inhalers over the European and North African markets were involved in this study, including the reference drug Foradil. Samples were prepared using a multistage liquid impinger (MsLI) and further analyzed by a validated HPLC-UV method to determine the delivered and the fine particle doses (FPDs). This study also examined the impact of freezing-thawing cycles on sample stability in terms of analytical purpose handling. Results: No substandard dry powder inhalers were identified among the medicinal products involved in this work. The delivered dose (DD) of assessed drugs varied from 8.33 to 9.69 mu g, while the FPD was between 1.86 and 3.35 mu g. As expected, this work confirmed that the capsule composition and the barrier properties of the primary packaging can affect the FPD of dry powder for inhalation use. Conclusions: The FPD of products C and B was, respectively, 17.4 and 14.2% superior to Foradil, products D and H had the closest values compared to the original drug, and product F was 34.5% inferior. Additionally, this work showed that a high FPD can be achieved using HPMC capsules and moisture-impermeable primary packaging.
Objective: To understand current treatment patterns and health care resource utilization (HRU) of women with locally advanced or metastatic breast cancer (advanced breast cancer; ABC) in Korea overall and within patients who had progressed with prior endocrine therapy (as first-line treatment for metastatic disease) and patients with no prior systemic treatment (for advanced disease). Methods: A chart review was conducted in 109 patients (women >= 18years old with HR+/HER2- ABC diagnosed between 2015 and 2017) from 11 hospitals. Anonymized data on patient characteristics, treatment patterns and HRU was abstracted. Results: Mean (range) age of all patients was 57.5 (40-81) years. Overall, the most common first-, second- and third-line systemic therapy after diagnosis of ABC were letrozole +/- palbociclib (51%), endocrine therapy (ET)+/- everolimus (42%) or chemotherapy (ChT) (39%), and ChT (68%), respectively. In patients progressed with ET (n = 33) and those with no prior systemic treatment (n = 52), the most common first-line treatments were letrozole (82%) and letrozole + palbociclib (42%), respectively. The percentage of patients with at least one grade 3 or higher adverse event during first-line therapy was 93.1% vs 39.2% in patients on a ChT based regimen (N = 29) vs. ET (N = 74). Overall, oncologist visits, at an annual rate of 9.27 (95% CI: 8.87, 9.69) visits per month, and hospitalizations, with an annual rate of 0.44 (95% CI: 0.36, 0.54), and mean (SD) length of stay of 14.3 (10.32) days, were the key drivers of HRU. Conclusions: These findings on real world HRU reflected clinical guidelines and severity of ABC. Results can inform future evaluations of new ABC treatments that estimate the health economic impact of their adoption in Korea.
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.
The National Association of Specialty Pharmacy (NASP) was scheduled to hold its 2021 Annual Meeting & Expo September 27–30, 2021;however, due to the ongoing COVID-19 pandemic, and out of concern for attendees, their families, their communities, and our front-line healthcare providers ,the conference was unfortunately cancelled. This year’s and poster presentation program provides an interactive forum to showcase research related to specialty pharmacy products and services. Many of this year’s s and posters focus on accomplishments, outcomes, and lessons learned as a result of COVID-19.
OBJECTIVE:Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). METHODS:A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). RESULTS:Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, p = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, p < .005). CONCLUSIONS:Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.
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.
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.
Acute repetitive seizures, also called seizure clusters, are common phenomena in patients with epilepsy. They are a burden on patients and their caregivers and may be very disruptive to the patients’ lives. They may progress to prolonged seizures or status epilepticus if they are not aborted as soon as possible. However, their definition, recognition, and classification still suffer from a lack of consensus among healthcare professionals in the field. This review aims to shed light on various aspects of seizure clusters with particular attention to their treatments.
Objective Pivotal clinical trials revealed good clinical efficiency of ocrelizumab while having a good safety profile in the management of multiple sclerosis (MS). However, real-world data of ocrelizumab in daily clinical practice remain scarce. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for MS in an Arab population in a real-world clinical setting. Methods In this retrospective single-center observational study in Qatar, we reviewed the medical records and analyzed the clinical and MRI data of all patients with relapsing-remitting MS (RRMS) and active secondary progressive MS (aSPMS)-between October 2017 through December 2020-who had received at least one infusion of ocrelizumab (Q-OCRE). Results A total of 60 MS patients were included (57 with RRMS, three SPMS). The Median follow-up period was 19 months (range, 1-32). The most common reason for switching to ocrelizumab was increased disease activity and three-quarters of the patients were on a previous disease-modifying drug (DMD). No evidence of disease activity (NEDA) status at year 1 was achieved in 73% of the cohort. Mild infusion-related reactions (IRR) and infections were reported (mainly upper respiratory tract infections followed by urinary tract infection) with a declining percentage over the follow-up applications. No severe side effects were observed. Conclusion Our real-world experience confirms good efficacy, tolerability, and safety of ocrelizumab in our Arab population.
Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.
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.
Abstract 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.
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.
The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age. Our patient was inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place and patient suffered pregnancy loss. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections and in pregnant woman counselling is needed to explain the potential risks and benefits.
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.
