Journal of Pharmaceutical Health Care and Sciences最新文献

Background: Guideline-directed medical therapy (GDMT) is important in heart failure management; however, polypharmacy itself may impact heart failure. Although measures against polypharmacy are needed, current discussion on unilateral drug tapering (including the drugs that should be tapered) is insufficient. In this study, we investigated the relationship between the number of prescribed GDMT drugs and prognosis in patients with heart failure.

Methods: In this single-centre retrospective study, 3,146 eligible patients with heart failure were included and divided into four groups based on the median number of prescribed GDMT drugs and the median number of drugs not included in the GDMT (ni-GDMT) at the time of hospital discharge. The definition of GDMT was based on various Japanese guidelines. The primary outcome was all-cause mortality within 3 years of hospital discharge.

Results: A total of 252 deaths were observed during the 3-year follow-up period. Kaplan-Meier analysis revealed that groups with GDMT drug count ≥ 5 and ni-GDMT drug count < 4 had the lowest mortality, and those with GDMT drug count < 5 and ni-GDMT drug count ≥ 4 had the highest mortality (log-rank, P < 0.001). Cox regression analysis revealed a significant association between ni-GDMT drug count and all-cause mortality, even after adjustment for number of GDMT medications, age, male, left ventricular ejection function < 40%, hemoglobin, albumin levels, and estimated glomerular filtration rate [HR = 1.06 (95% CI: 1.01-1.11), P = 0.020]. Conversely, the GDMT drug count was not associated with increased mortality rates.

Conclusions: The ni-GDMT drug count was significantly associated with 3-year mortality in patients with heart failure. Conversely, the GDMT drug count did not worsen the prognosis. Polypharmacy measures should consider ni-GDMT drug quantity to improve the prognosis and outcomes in patients with heart failure.

Background: We aimed to compare anticoagulation control and outcomes between usual medical care (UMC) and pharmacist-led anticoagulation services (PLAS) in patients receiving warfarin at the Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia.

Methods: A quasi-experimental study was conducted, including 350 (66.7%) and 175 (33.3%) patients from the UMC and PLAS groups, respectively, from 525 patients. The time in therapeutic range (TTR) was determined using the Rosendaal method, with a TTR ≥ 65% set as the cut-off for optimal anticoagulation. The two-sample Wilcoxon rank-sum (Mann-Whitney U) test was used to compare continuous variables between groups. Categorical variables were compared between groups using Pearson's chi-square test or Fisher's exact test. Logistic regression and negative binomial regression analyses were conducted to identify the factors associated with suboptimal TTR and secondary outcomes, respectively, at the p values < 0.05, and 95% confidence interval (CI).

Results: Compared with the UMC group, the patients in the PLAC group showed a significantly higher median (IQR) TTR [60.89% (43.5-74.69%) vs. 53.65% (33.92-69.14%), p < 0.001]. A significantly higher optimal TTR (≥ 65%) was achieved in the PLAC group (41.7% vs. 31.7%) than in the UMC group (p = 0.002). The odds of having a poor TTR were reduced by 43% (AOR = 0.57, 95% CI = 0.36-0.88, p = 0.01) among patients in the PLAC group compared to those in the UMC group. There were no statistically significant differences in the secondary outcomes between the groups, except for all-cause emergency visits (p = 0.003). The incidence of bleeding events decreased by 3% (IRR = 0.97, 95% CI = 0.96-0.99, p < 0.001) for every increase in INR monitoring frequency. The incidence of thromboembolic events increased by a factor of 15.13 (IRR = 15.13, 95% CI = 1.47-155.52, p = 0.02) among patients with a high-risk CHA₂DS₂-VASc score compared with those with a moderate score.

Conclusion: Patients in the PLAC group had a significantly higher median TTR than those in the UMC group did. There were no statistically significant differences in the secondary outcomes between the groups, except for fewer all-cause emergency department visits in the PLAC group.

Background: Anamorelin, a drug to treat cancer cachexia, binds to ghrelin receptors and improves body weight and appetite. In clinical trials in Japan, patients experienced a 10.7% frequency of stimulant conduction system depression as a severe side effect. Although rare, anamorelin sometimes causes fatal arrhythmias. Because patients with cancer cachexia are often underweight, data on the safety of anamorelin in obese patients are lacking. We report a case of QT interval prolongation after anamorelin administration to an obese patient with non-small cell lung cancer.

Case presentation: A female patient with a body mass index of 30 kg/m2 underwent immunotherapy for lung adenocarcinoma. She presented with severe weight loss, anorexia, and fatigue. She had no history of heart disease. On day 12, after administration of anamorelin 100 mg once daily, the patient developed nausea, diarrhea, and anorexia, which were considered cancer immunotherapy-induced immune-related adverse events, and she was admitted to the hospital. An electrocardiogram (ECG) on admission showed a QTc interval of 502 ms. On admission, her hepatic function was Child-Pugh class B, and anamorelin was discontinued the next day. On day 3 after anamorelin discontinuation, the QTc interval was prolonged by up to 557 ms, then decreased to 490 ms on day 6, and improved to 450 ms on day 16. Re-administration of anamorelin was avoided.

Conclusions: When administering anamorelin to obese patients, we should be aware of the potential for stimulatory conduction system depression, as in underweight patients. Therefore, we should monitor patients by ECG from the early stages of anamorelin administration. Anamorelin is lipophilic, and its volume of distribution is increased in obese patients. Consequently, obese patients may continue to have QT interval prolongation after discontinuation of anamorelin, requiring long-term side-effect monitoring.

Background: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose.

Methods: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP).

Results: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose.

Conclusions: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications.

Background: Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function.

Methods: We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool.

Results: Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I² = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia.

Conclusions: Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.

Background: Ganciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice.

Case presentation: In this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia. Valganciclovir administration was initiated at a conventional dose of 450 mg/day on postoperative day 43 but was reduced to 450 mg/2 days on postoperative day 69 because of a decrease in white blood cell count and an increase in trough ganciclovir concentration. Subsequently, the valganciclovir dose adjustment was switched from label-indicated renal function-guided dosing to TDM-based dosing, targeting a trough level of 300-800 ng/mL. This target range was determined through deliberations with infectious disease specialists and pharmacists based on previously reported data. The TDM-based dose adjustment successfully prevented cytomegalovirus reactivation without causing significant adverse effects. Valganciclovir prophylaxis was completed on postoperative day 256, and the patient was transferred to another hospital for rehabilitation.

Conclusions: The findings of the present case suggest that TDM-based dosing could be helpful for clinicians in optimizing the prophylactic administration of valganciclovir in patients undergoing lung transplantation.

Background: Patient satisfaction is a crucial humanistic outcome metric in pharmacy services. There was a lack of evidence on patients' satisfaction with pharmacy services in Gamo zone among users and nonusers of the CBHI scheme. Therefore, the aim this study is to compare the level of patient satisfaction with pharmacy services among users and nonusers of community based health insurance scheme at public health facilities in Gamo zone, South Ethiopia.

Method: A facility based comparative cross sectional study design with mixed approach was conducted from June 1 to 30, 2023. A total of 522 study participants and 16 key informants were included as the sample size for quantitative and qualitative study, respectively. The quantitative data was gathered from the study participants who visited the outpatient pharmacy department during the study period by using a simple random sampling technique, while the purposive sampling technique was used to select clients and key informants for the qualitative study. The adjusted odds ratio (AOR) was used to measure the association between independent variables and patient satisfaction toward outpatient pharmacy services at the P values < 0.05 and 95% confidence interval (CI).

Results: From the total of study participants, 195 (73.9%) of insured and 175 (67.8%) of noninsured clients were satisfied with pharmacy services offered at public health facilities. The gender of insured (95% CI = 2.00-12.36, (p 0.01)), and noninsured (95% CI = 0.658-2.881, (p 0.02)), waiting time of insured (95% CI = 0.057-0.766, (p 0.0027)), and noninsured (95% CI = 0.084-0.925, (p 0. 0021)) and premium affordability of insured (95% CI = 0.0605-4.860, (p 0.00)) were significantly associated factors with client satisfaction at p < 0.05 and 95% CI. Based on qualitative finding, as member of the CBHI scheme, the members had a greater opportunity to receive a good pharmacy services, because they were more familiar with the physicians and the institutions.

Conclusion: The clients with insurance perceived high level of satisfaction with pharmacy services in public health facilities than noninsured. The gender and waiting times at outpatient pharmacy department for both groups of study participants and the premium affordability for the insured groups of clients were factors affecting client satisfactions with pharmacy services.

Background: People living with human immunodeficiency virus (PLWH) require high rates of medication adherence to antiretroviral therapy (ART) for a successful treatment outcome. Understanding the factors associated with incomplete adherence among those receiving integrase strand transfer inhibitor-containing single-tablet regimens (INSTI-STRs) is crucial for improving treatment outcomes. This study aimed to identify the factors contributing to incomplete ART adherence among Japanese PLWH receiving INSTI-STRs.

Methods: This multicenter cross-sectional study was conducted at 11 Japanese institutions as an anonymous survey. ART adherence was assessed using a self-reported questionnaire. We defined incomplete ART adherence as missing ≥ 1 dose of antiretroviral drugs (ARVs) over the past month. The factors associated with incomplete ART adherence were assessed using logistic regression analysis. Additionally, we investigated the associations between patients' satisfaction score with and need for ARVs and their adherence to ART.

Results: The final analysis included data of 387 patients who were treated with INSTI-STRs. Multivariate logistic regression demonstrated significant association of younger age (adjusted odds ratio [aOR], 0.79; 95%confidence interval [CI]: 0.64-0.99 for each 10-year increment) with incomplete ART adherence. Additionally, female sex (aOR, 3.98; 95%CI: 1.36-11.60); depressive symptoms (mild depression: aOR, 1.68; 95%CI: 1.001-2.82, moderate depression: aOR, 2.98; 95%CI: 1.35-6.53, and severe depression: aOR, 8.73; 95%CI: 1.38-55.00 vs. minimal depression); were also significantly associated with incomplete ART adherence when compared with the reference categories. Concomitant medication usage was significantly associated with a lower rate of incomplete ART adherence (1-4 medications: aOR, 0.53; 95%CI: 0.31-0.89 and ≥ 5 medications: aOR, 0.30; 95%CI: 0.13-0.70 vs. no concomitant medication usage). In the incomplete ART adherence group, satisfaction scores for various aspects were significantly lower. Furthermore, a lower proportion of patients in the incomplete ART adherence group preferred the option of "taking tablets daily and visiting the hospital every 3 months," compared to those in the complete ART adherence group (p = 0.008).

Conclusions: This study demonstrated that factors associated with incomplete ART adherence include younger age, female sex, no concomitant medication, and depressive symptoms. Despite ART simplification, incomplete adherence among PLWH receiving INSTI-STRs, remains a challenge, requiring additional actions.

Background: Ipilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs).

Case presentation: A 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention.

Conclusions: This case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Background: COMISA is a common disorder that results in nighttime awakenings ,daytime sleepiness and PAP intolerance. Cognitive behavioral therapy for insomnia is used to improve PAP adherence and no medication has been evaluated in such population yet. Melatonin with its chronobiotic and antioxidant effects may have potential benefits on COMISA consequences at the appropriate dose and time. This study aimed to evaluate the effect of melatonin on sleep quality, daytime sleepiness and PAP Compliance in patients with COMISA.

Methods: This double-blind placebo trial randomly assigned eligible OSA patients who suffered from insomnia despite using PAP for over a month to receive either melatonin 10 mg or placebo. The primary outcomes were measured by changes in the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ-10) over one month. Adherence to PAP was measured by the results of the PAP device reports on the average length of time and number of nights that the device was used.

Results: Thirty patients were enrolled in the study after randomization. The melatonin arm showed significant improvement in all four primary outcomes compared to the placebo arm. The PSQI score was 3.836±1.839 in the melatonin arm versus 10.522±3.626 in the placebo arm (Pvalue<0.001). The ISI score was 8.476±3.568 in the melatonin arm versus 14.47±4.50 in the placebo arm (Pvalue<0.001). The ESS score was 6.854±4.334 in the melatonin arm versus 13.298±5.119 in the placebo arm (Pvalue<0.001). The FOSQ-10 score was 24.93±5.02 in the melatonin arm versus 19.87±4.24 in the placebo arm (Pvalue= 0.006). Additionally, nighttime consequences such as sleep latency and awakenings showed significant improvement in the melatonin arm. PAP devices results revealed improvement in duration of PAP use overnight.  CONCLUSIONS: Administering melatonin has been shown to improve self-reported sleep quality and PAP adherence in patients with COMISA.

Trial registration: Registration number IRCT20220105053635N1 was issued by the Iranian Registry of Clinical Trials (IRCT).