Current Medical Research and Opinion最新文献

Introduction: Diabetes Mellitus is a chronic disease characterised by elevated plasma glucose (PG) levels. HbA1c has been widely utilized for diabetes diagnosis. However, certain conditions restrict its use. In such cases, plasma glucose (PG) measurements and self-monitoring blood glucose (SMBG) are recommended. This case series highlights the importance of considering both HbA1c and PG or SMBG in the evaluation of patients with diabetes.

Case report: This case series presents three cases of patients with diabetes who exhibited a discrepancy between PG and HbA1c levels. Only one patient demonstrated isolated microcytosis, while the remaining two had completely normal hematologic profiles. Due to this discrepancy, hemoglobin electrophoresis was conducted, revealing various hemoglobinopathies in all cases.

Conclusion: For patients with discrepancies between PG levels and HbA1c, we suggest a thorough evaluation that includes consideration of potential hemoglobinopathies. These hemoglobin variants can present with isolated microcytosis or entirely normal hematologic parameters and may lead to falsely low HbA1c values. In cases of discordance between PG and HbA1c, hemoglobin electrophoresis can serve as a valuable diagnostic tool. Identifying hemoglobinopathies before determining treatment regimens can help mitigate the risk of complications from inadequate treatment, and awareness of HbA1c limitations allows clinicians to use both HbA1c and PG/SMBG to optimize diabetes management and minimize the risk of diabetic complications.

Objective: To explore the efficacy and safety of brexpiprazole for the treatment of agitation symptoms in clinically relevant subgroups of patients with dementia due to Alzheimer's disease.

Methods: Data were pooled for brexpiprazole (2 or 3 mg/day) and placebo from two international, randomized, double-blind trials in adults with a clinical diagnosis of Alzheimer's dementia with mild-to-severe cognitive dysfunction and with agitation (ClinicalTrials.gov identifiers: NCT01862640, NCT03548584). Change in agitation frequency over 12 weeks was measured using the Cohen-Mansfield Agitation Inventory (CMAI). Safety measures included treatment-emergent adverse events (TEAEs). In this post hoc analysis, thirteen clinically relevant subgroups were investigated based on care setting (institutionalized, non-institutionalized), severity of cognitive dysfunction (mild/moderate, severe), co-occurring behavioral symptoms (psychosis, depression, anxiety, irritability, sleep disturbance), and use of concomitant medications for dementia (acetylcholinesterase inhibitor, memantine) and psychiatric conditions (antidepressant, benzodiazepine).

Results: In the randomized sample (N = 621), mean age was 74 years (range 55-90 years), 344 (55.4%) participants were female, and 277 (44.6%) were male. Over 12 weeks, brexpiprazole showed numerically greater reduction in agitation frequency than placebo in 12 of 13 subgroups. The only exception was "concomitant benzodiazepines", which was a small subgroup (n = 71), but showed efficacy for brexpiprazole in secondary analyses. The largest differences in favor of brexpiprazole versus placebo were for the concomitant antidepressant, co-occurring sleep disorder, and co-occurring psychosis subgroups. The overall incidence of TEAEs was generally consistent across subgroups.

Conclusion: In these exploratory analyses, brexpiprazole reduced symptoms of agitation across a wide range of patients with agitation associated with dementia due to Alzheimer's disease.

Objective: Several vaccines are recommended for 16-23-year-olds in the United States, but coverage varies widely across these vaccines. Previous studies have indicated that routine healthcare visits are associated with vaccination uptake. This study aimed to describe healthcare visit patterns among 16-23-year-olds to identify challenges and inform opportunities to reach adolescents and young adults for vaccination.

Methods: A descriptive, retrospective database analysis was conducted of commercially insured and Medicaid-insured 16-23-year-olds from 2019-2022 using IQVIA's PharMetrics^® Plus claims database and open-source Longitudinal Prescription/Medical claims databases. The proportion of 16-23-year-olds with healthcare provider (HCP) visits, visit types, provider types involved, visits including vaccination, and specific vaccines delivered were analyzed.

Results: In 2022, 68.2% of commercially insured 16-23-year-olds had ≥1 HCP visit. Most commercially insured and Medicaid-insured individuals with ≥1 HCP visit had sick visits (72.9-80.6%). The proportion of individuals with preventative visits was lower as age increased (commercially insured: 73.2% at 16, 67.4% at 18, 56.3% at 19, and 45.3% at 23 years). Lower proportions of individuals with preventative visits with increasing age were also seen among Medicaid-insured individuals, ranging from 53.7% at 16 years to 28.0% at 23 years. Among 16-18-year-olds with ≥1 HCP or pharmacy visit in 2022, 52.6% in the commercial cohort and 33.0% in the Medicaid cohort had ≥1 visit that involved vaccination; for 19-23-year-olds, these proportions were 34.5% and 25.6%, respectively. Vaccination rates by vaccine type were largely aligned with the ages specified by recommendations, but nonetheless were low.

Conclusion: Approximately one-third of commercially insured 16-23-year-olds did not have an annual HCP visit, and among commercially insured and Medicaid-insured individuals who did have visits, a substantial proportion did not have preventative visits; this proportion was higher with increasing age. The proportions of visits with vaccination were particularly low for 19-23-year-olds. Targeted interventions to promote routine visits, including framing these as opportunities for immunization, may help to increase vaccination uptake; based on the findings of this analysis, these efforts should consider age-specific shifts in health-seeking behaviors.

Chronic kidney disease (CKD) is a global issue that raises inflammation and heightens the risk of progressing to advanced CKD, requiring renal replacement therapy. It also significantly increases the likelihood of cardiovascular and vascular diseases, hospitalizations, functional decline, and reduced quality of life, particularly in older adults. CKD prevalence rises with age, affecting 25-30% of older adults. Despite that, the fact is that CKD is underdiagnosed in this population. Diagnosing CKD in older patients is difficult because accurate tests are limited, common serum creatinine-based formulas depend on muscle mass (often low in this group), and age-related renal function decline further complicates assessment. Comprehensive management can help achieve therapeutic goals in the old population with CKD through assessments and care plans. This care includes a combination of lifestyle changes, cardiovascular risk factors control, the use of drugs with proven renal and cardiovascular benefits, as well as the adequate management of specific clinical conditions, including the general clinical comorbidities, renal-related conditions and recognition of geriatric syndromes, helping patients manage their condition and involving them in decisions about their care. In this narrative review, the epidemiology, clinical profile and management of CKD in the old population are updated.

Objective: Patient involvement in pharmaceutical industry-sponsored publications is a rapidly evolving practice. It is supported by industry guidelines, but currently inconsistent across organizations. This study aimed to qualitatively map the landscape of current practices and gaps in patient involvement in peer-reviewed journal publications of pharmaceutical industry-sponsored research, and to define the specific roles and activities in which patients are involved.

Methods: This qualitative, patient-led study was conducted using semi-structured interviews with purposively sampled experts in patient engagement and publications, including patients. Interviews were conducted online, transcribed, and thematically analysed. Landscape elements were visually mapped, and themes were generated through an inductive and experientially situated thematic analysis.

Results: Interviews were conducted with 20 participants recruited globally, with a majority from the United Kingdom. Participants represented diverse stakeholder categories and reported patient involvement across all stages and aspects of the publication lifecycle, with patients both as external consultants and as professionals working within the system. Five overarching themes and 20 sub-themes were identified, including: patient identities and roles; principles and values; processes and practices; variations over time and across organizations; and impact. Significant gaps were identified in consistency, quality, and scale, for example including gaps in infrastructure barriers and diversity.

Conclusions: Patient involvement in pharmaceutical publications is actively happening across the publication lifecycle and is rapidly growing and evolving. This study provides an evidence base via a qualitative mapping of the experiential landscape and highlights the need for established best practices to support consistency and quality in meaningful patient involvement in publications.

Objective: ESCAPE-TRD, a randomized phase 3b trial, compares the efficacy and safety of esketamine nasal spray (NS) and extended-release (XR) quetiapine, both in combination with ongoing oral antidepressant (OAD) treatment, among individuals with treatment-resistant depression (TRD). Although prior analyses used the clinician-rated MADRS, the comparative efficacy of esketamine NS vs. quetiapine XR using a patient-reported instrument to assess TRD severity among a subgroup treated according to US label is unknown.

Methods: ESCAPE-TRD data were evaluated using the patient-rated Patient Health Questionnaire-9 (PHQ-9) instrument for individuals receiving treatment consistent with US prescribing information (NCT04338321). The main outcome was remission at weeks 8 and 32. Additional outcomes included response, time to first remission, time to first response, time to confirmed remission, time to confirmed response, and change in PHQ-9 score from baseline.

Results: A significantly higher proportion of individuals in the esketamine NS group than in the quetiapine XR group achieved remission and response at week 8 (remission: 19.3% vs. 12.2%; RD [95% CI]: 7.1% [1.5%, 12.8%]; p = 0.013; response: 49.4% vs. 32.8%, RD [95% CI]:16.6% [9.0%, 24.1%]; p < 0.001). At 32 weeks, a significantly higher proportion of individuals in the esketamine NS group achieved remission and response compared to the quetiapine XR group (remission: 34.8% vs. 18.1%, RD [95% CI]: 16.7% [9.9%, 23.4%]; p < 0.001; response: 58.9% vs. 40.3%, RD [95% CI]:18.5% [10.9%, 26.2%]; p < 0.001).

Conclusion: Using patient-reported PHQ-9 scoring to evaluate ESCAPE-TRD results, esketamine NS produced superior short- and long-term efficacy vs. quetiapine XR among individuals with TRD treated according to US label.

Objective: HIF-PHI inhibitors, including daprodustat, have expanded treatment options for patients with renal anaemia in Japan. This analysis examines real-world utilization of daprodustat in Japan, for which data are currently lacking.

Methods: This retrospective cohort study analyzed patient characteristics, treatment patterns, and management of renal anaemia in individuals aged >15 years who were treated with daprodustat between 1 August 2020 and 1 July 2023 using an anonymized electronic medical record database. Patients were assigned to dialysis-dependent (DD) and nondialysis-dependent (ND) cohorts.

Results: This study included 1299 patients (111 DD cohort; 1188 ND cohort). Mean age was 71.0 and 79.2 years in the DD and ND cohorts, respectively. In both cohorts, hypertension, heart failure, oesophageal gastric erosion, and type 2 diabetes mellitus were frequent comorbidities. In the DD cohort, 31.5% of patients had Hb levels of 9-10 g/dL at baseline and in the ND cohort 35.9% had Hb levels <9 g/dL at baseline. Prior to the index date, 72 patients in the DD cohort (64.9%) and 635 patients (53.5%) in the ND cohort were treated for anaemia. In patients who switched from erythropoiesis-stimulating agents to daprodustat, mean haemoglobin increased from 9.9 g/dL at baseline to 10.8 g/dL in the DD cohort (n = 23; Wilcoxon sign-ranked test [WSRT] p = 0.0148) and from 9.6 g/dL at baseline to 10.4 g/dL in the ND cohort (n = 92; WSRT p < 0.0001) 28 weeks after daprodustat initiation.

Conclusion: Approximately a third (DD) to almost half (ND) of patients with renal anaemia were not receiving treatment for anaemia. An increase in haemoglobin levels was observed after initiation of daprodustat, including in patients previously treated with erythropoiesis-stimulating agents, however causality cannot be confirmed due to lack of a control group.

Objective: Molnupiravir (MOV), an oral antiviral, is prescribed to treat adult patients with mild-to-moderate COVID-19 at risk of progressing to severe disease. Previous systematic literature reviews (SLRs) have evaluated the effectiveness of MOV in the general population; however, evidence on high-risk population is lacking. This SLR assessed the real-world effectiveness of MOV for reducing the progression to severe COVID-19 outcomes in clinical settings, including high-risk or special populations (such as patients with type 2 diabetes, chronic respiratory diseases, immunocompromised conditions, older adults, and nursing home residents) who have limited alternative COVID-19 treatment options.

Methods: We searched EMBASE and PubMed databases for studies published between 1 January 2021 and 24 May 2024, using predefined search terms related to MOV. Studies comparing MOV-treated with untreated groups of non-hospitalized adults at risk of progression to severe COVID-19 outcomes (hospitalization, death, and the composite of hospitalization/death) were included. Risk of bias of the included studies was assessed using the ROBINS-I tool.

Results: Twenty-one general and special population studies were included. General population studies (n = 16) showed that MOV reduced the risk of death, hospitalization, and hospitalization/death. Special population studies (n = 10; five additional and five general population articles with subgroups of interest) also showed that MOV reduced the risk of the same outcomes, with a more pronounced effect in older adults (≥60 years). The wide range of risk reduction observed might be attributed to variability in COVID-19 hospitalization guidelines and vaccination status.

Conclusions: Findings from this SLR suggest that MOV may reduce the risk of hospitalization, death, and hospitalization/death compared with untreated groups, including high-risk adults with underlying comorbidities. Further studies are needed to confirm the effectiveness of MOV in high-risk or special populations.

Objective: For people with schizophrenia and their caregivers, anxiety is among the top symptoms for which they would like an effective treatment. The aims of this post hoc analysis of clinical trial data were to characterize the efficacy, safety and tolerability of brexpiprazole on anxiety symptoms in adults with schizophrenia, and to investigate the relationships between anxiety symptoms, functioning, and patient life engagement.

Methods: Data were pooled for brexpiprazole 2-4 mg/day and placebo from three six-week, randomized, double-blind trials of brexpiprazole in adult inpatients with schizophrenia (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380) and for brexpiprazole 1-4 mg/day from two 52-week, open-label extension trials (NCT01397786, NCT01810783). People with comorbid anxiety disorders were not enrolled. In this post hoc analysis, anxiety was measured by a single item (G2) of the Positive and Negative Syndrome Scale (PANSS), functioning was measured by the Personal and Social Performance scale, and patient life engagement was measured by a 14-item PANSS subset. Least squares mean changes from baseline were calculated using a mixed model for repeated measures. Anxiety response was defined using two definitions: (1) PANSS G2 improvement of ≥1 point (a clinically interpretable score change) from baseline to Week 6, and (2) PANSS G2 score of <3 points (anxiety symptoms reduced to "minimal" or "absent") at Week 6 for the subgroup who had anxiety at baseline (G2 score ≥3). This was an exploratory, hypothesis-generating analysis with no correction for multiple comparisons.

Results: Anxiety at baseline (G2 score ≥3) was present in 763/868 (87.9%) participants on brexpiprazole, and 449/517 (86.8%) on placebo. At Week 6, least squares mean change from baseline in G2 score favored brexpiprazole versus placebo: mean difference, -0.19; 95% confidence interval, -0.33 to -0.06; p = .005; Cohen's d effect size, 0.19. Anxiety response for brexpiprazole and placebo, respectively, was shown in 547/863 (63.4%) and 291/515 (56.5%) participants (p = .012; response definition 1), and 283/541 (52.3%) and 135/303 (44.6%) participants (p = .036; response definition 2). Functioning and patient life engagement improved regardless of whether participants' anxiety improved. Long-term data suggested maintenance of treatment effects. Adverse events were consistent with prior analyses.

Conclusion: Exploratory analyses suggest that brexpiprazole may help in the management of anxiety symptoms, functioning, and patient life engagement - important outcomes for people with schizophrenia.