Drugs - Real World Outcomes最新文献

Background and objective: Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer.

Methods: This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups.

Results: Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group.

Conclusions: The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.

Introduction: Both the induction and inhibition of cytochrome P450 are associated with multiple pharmacological interactions, which can lead to loss of efficacy or increase the risk of adverse drug reactions.

Objective: The aim was to determine the prescription patterns of cytochrome P450-inducing and -inhibiting drugs and their contraindicated and major pharmacological interactions in a group of patients from Colombia.

Methods: This cross-sectional observational study included patients who received drugs that induce or inhibit metabolism and examined their contraindicated and major pharmacological interactions. The patients were identified from a population-based database of drug dispensing. Patients were included between December 1 and December 31, 2021. Inhibitors and inducers of cytochrome P450 were classified based on FDA (Food and Drug Administration) guidelines. Drug interactions were identified using the Micromedex® database. Descriptive, bivariate and multivariable analysis was performed.

Results: A total of 63,433 patients were analyzed. Antiseizure medications (35.9%) and antifungals (27.6%) were the most used inducers and inhibitors. A total of 30.1% of patients had potential contraindicated or greater interactions. The following factors were associated with a higher probability of presenting a potential pharmacological interaction: being male (OR 1.14; 95% CI 1.10-1.19), aged 18-39 years (OR 1.77; 95% CI 1.67-1.89) or 40-64 years (OR 1.64; 95% CI 1.56-1.72), having neurological diseases (OR 1.28; 95% CI 1.21-1.35), having psychiatric diseases (OR 3.84; 95% CI 3.58-4.13), having rheumatologic diseases (OR 1.32; 95% CI 1.23-1.41), receiving comedications with statins (OR 1.14; 95% CI 1.08-1.19), receiving comedications with analgesics (OR 1.33; 95% CI 1.27-1.38), receiving comedications with antiparasitics (OR 2.88; 95% CI 2.66-3.11) and an increase in the number of medications (OR 1.24; 95% CI 1.23-1.25).

Conclusion: Among the users of cytochrome P450 inhibitors and inducers, potential contraindications and greater interactions are very common, especially in men under 65 years of age with comorbidities and polypharmacy.

Background: The rapidly changing policy climate related to cannabis legalization has led to drastic changes in cannabis use in the United States (US). Medical cannabis use is increasing overall, but at a faster rate among older adults compared to other age groups.

Objective: The aim was to investigate older adults' cannabis use behaviors and attitudes around disclosing medical cannabis use to their primary healthcare providers (HCPs).

Methods: Nineteen older adults (ages 65+ years) with self-reported medical cannabis use were recruited from flyers posted in ambulatory clinics in San Diego, CA. Surveys and semi-structured interviews on cannabis use were completed. A multi-methods approach was used to analyze data.

Results: Participants' mean age was 75.3 years; 52.6% identified as women, and 89.5% as White. Cannabis was used by all participants to treat pain and by 75% for insomnia, with 25-33% reductions in use of prescription medications to treat these symptoms. Approximately 89% reported their primary HCPs were aware of their cannabis use, and 84.2% felt very comfortable/comfortable talking to HCPs about cannabis. Common themes from interviews included participants (1) being motivated to disclose cannabis use to their HCPs to seek medical advice on dosing, side effects, and benefits of cannabis, (2) feeling comfortable disclosing cannabis use as legalization has eased the stigma around cannabis use, and (3) perceiving mostly neutral attitudes from HCPs on their cannabis use.

Conclusion: The study emphasizes the pivotal role of HCPs as educators in addressing patient inquiries about cannabis, underlining the need for equipping healthcare professionals with evidence-based knowledge through education and training initiatives.

Introduction: Older people are on average more susceptible to the adverse effects of psychotropic drugs, but addressing older people as a homogenous group based on age alone can be misleading when exploring psychotropic drug use. This study aimed to describe psychotropic drug use and associated factors among community-dwelling older people who had been acutely admitted to hospital.

Methods: This cross-sectional study was based on a sample of 300 community-dwelling people 75 years or older who had been admitted to the acute medical ward at Umeå University Hospital at any time from September 2018 to October 2021. Data on medication use were obtained from electronic medical charts, and psychotropic drug use was presented as user proportions, both in terms of individual substances and drug classes. Associations between psychotropic drug use and factors comprising sex, age, cohabitation, comorbidities and multi-dose dispensing (MDD) of medicines were analysed through logistic regression.

Results: Approximately 50% of the individuals used at least one psychotropic drug, and 18% used two or more such medicines. Zopiclone displayed the highest user proportion of all psychotropics (18.3%), followed by mirtazapine (11.3%) and zolpidem (9.7%). Of note, zolpidem was more prevalent among the females than among the males (p = 0.006). Regarding other sex differences, 55 and 38% of the females and males, respectively, used at least one psychotropic drug (p = 0.004). A similar pattern was observed regarding sedatives and hypnotic drugs exclusively (p = 0.048). In the regression analysis, female sex (adjusted odds ratio [OR] 2.05 [95% confidence interval {CI} 1.22-3.42]) and MDD (adjusted OR 2.20 [95% CI 1.23-3.93]) were positively associated with psychotropic drug use.

Conclusion: The most common psychotropic drugs used by community-dwelling older people admitted to the acute medical ward were hypnotic drugs and antidepressants. Regarding patient factors, female sex and MDD system were positively associated with psychotropic drug use. Further studies concerning those two factors in relation to potential overprescribing could provide a better picture on how to optimize psychotropic drug use among acutely admitted vulnerable older people.

Background: Gabapentinoids (GBP) and benzodiazepines (BZ) are commonly prescribed in older adults and their package inserts list edema and vertigo as adverse drug reactions. These adverse drug reactions may be treated with symptomatic drug therapies without discontinuing the culprit drugs or decreasing their dose, thereby initiating a prescribing cascade and often resulting in polypharmacy. Whether prescribing cascades occur in the treatment of edema and dizziness among Japanese patients treated with GBP and BZ has not been investigated, including treatment with mirogabalin, a class drug of GBP marketed in Japan.

Objective: We aimed to investigate prescribing cascades with GBP-induced and BZ-induced edema and dizziness treated with loop diuretics (LD) and anti-vertigo drugs (AVD), respectively, among older adults.

Methods: A prescription sequence symmetry analysis design was used to detect signals of prescribing cascades associated with edema and dizziness induced by GBP and BZ (exposure drugs). Loop diuretics and AVD were the outcome drugs used to identify prescribing cascades following the initiation of exposure drugs. The study population consisted of enrollees of a large-scale health claims database provided by DeSC Healthcare, Inc., between April 2014 and March 2021. Subjects eligible for a prescription sequence symmetry analysis were patients aged ≥ 65 years prescribed an outcome drug within 90 days before and after exposure drug initiation. A signal of a prescribing cascade was detected if secular trend-adjusted sequence ratios were statistically significant on comparison of the frequencies of outcome drug initiation before and after exposure drug initiation.

Results: We identified 2671 patients with prescriptions of a GBP-LD combination, 4009 with a GBP-AVD combination, 8675 with a BZ-LD combination, and 9462 with a BZ-AVD combination. The adjusted sequence ratios for GBP-LD and BZ-LD cascades were significantly larger than one (adjusted sequence ratio [95% confidence interval], 1.69 [1.56-1.83]; 1.35 [1.29-1.41], respectively), indicating positive signals of prescribing cascades. No signal was detected for the GBP-AVD or BZ-AVD cascade (0.89 [0.83-0.94]; 0.90 [0.87-0.94], respectively). The adjusted sequence ratio for the mirogabalin cascade was higher than that for pregabalin (2.23 [1.84-2.71] vs 1.59 [1.46-1.73]).

Conclusions: Our study provides good evidence that LD-prescribing cascades associated with edema would be a class effect of GBP and BZ. Edema emerging around 1 month after GBP initiation should be carefully differentiated from pathological edema, and undue LD prescription as a prescribing cascade should be avoided.

Background: Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings.

Objectives: This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE.

Methods: A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013-2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures.

Results: Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively.

Conclusions: In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively.

Background: For patients with metastatic non-small cell lung cancer, timely molecular testing is essential to determine the appropriate course of therapy. Initial treatment with platinum chemotherapy and/or an immune checkpoint inhibitor (ICI) is the standard of care for patients without actionable genomic alterations.

Objective: We aimed to assess treatment patterns and clinical outcomes among patients with metastatic non-small cell lung cancer, no actionable genomic alterations, and with prior ICI and platinum-based chemotherapy in a community oncology setting.

Methods: This retrospective observational study examined electronic health records from adult patients with an initial metastatic non-small cell lung cancer diagnosis without actionable genomic alterations from 2017 to 2019. Patients had received a subsequent line of therapy (LOT) [index] after discontinuing platinum-based chemotherapy plus an ICI in the previous one or two LOTs. Patient demographics and clinical characteristics were analyzed descriptively. Clinical outcomes were evaluated using Kaplan-Meier analyses.

Results: Among the study population (n = 961), the most common index LOT regimens were non-platinum-based chemotherapies (57.3%), platinum-based chemotherapies (12.9%), ICI-based chemotherapies (12.7%), platinum + ICI-based chemotherapies (9.4%), and other (7.7%). The most common post-index LOT regimens were non-platinum based (61.2%), ICI based (15.3%), platinum based (10.7%), platinum + ICI based (3.2%), and other (2.5%). Median time to treatment discontinuation, time to next treatment, and overall survival were numerically longest with index LOT ICI-based regimens (6.5, 9.9, and 18.9 months, respectively) and shortest with platinum-based regimens (2.8, 5.3, and 8.0 months, respectively) and non-platinum-based regimens (2.6, 5.0, and 7.8 months, respectively).

Conclusions: Among patients with metastatic non-small cell lung cancer without actionable genomic alterations previously treated with platinum + ICIs, non-platinum chemotherapy agents were most commonly prescribed in the index LOT. Clinical outcomes including time to treatment discontinuation, time to next treatment, and overall survival were short, highlighting the unmet need for more effective later-line treatments.

Background and objectives: Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes.

Methods: This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed.

Results: The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016).

Conclusion: Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Background: Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice.

Objectives: The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity.

Methods: An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4 ng/mL, or serum K+ > 5 mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1.

Results: Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p < 0.05) including higher mean SDC (3.41 ± 1.63 vs 2.87 ± 1.17), higher mean potassium (5.33 ± 1.48 vs 4.55 ± 0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p < 0.01) and they had shorter intensive care unit lengths of stay (12.4 ± 20.3 vs 24.4 ± 28.7 days; p = 0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively.

Conclusions: Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.