Improving Medication Management for Inpatients with a Secondary Diagnosis of Parkinson Disease.

ABSTRACT: Patients who have Parkinson disease require individualized medication regimens to optimize care. A review of the medication management of patients admitted to a tertiary care hospital with a secondary diagnosis of Parkinson disease found significant departures from the patients' home regimen. Medication regimens are often altered by health care teams unfamiliar with Parkinson disease-specific care in order to conform to standard hospital medication orders and administration times, potentially resulting in increased patient falls, delirium, and mortality.A nurse-led multidisciplinary team consisting of pharmacy, nursing, informatics, neurology, and quality personnel implemented a quality improvement (QI) project between July 2020 and July 2022 to identify patients with Parkinson disease, including those with a secondary diagnosis and those undergoing deep brain stimulation, and customize medication management in order to reduce length of stay, mortality, falls, falls with harm, and 30-day readmissions. The QI project team also evaluated patient satisfaction with medication management.Among patients with a secondary diagnosis of Parkinson disease, the proportion who had medication histories conducted by a pharmacy staff member increased from a baseline of 53% to more than 75% per month. For all patients with Parkinson disease, those whose medication history was taken by a pharmacy staff member had orders matching their home regimen 89% of the time, whereas those who did not had orders matching the home regimen only 40% of the time. Among patients with a secondary diagnosis of Parkinson disease, the length-of-stay index decreased from a baseline of 1 to 0.94 and observed-to-expected mortality decreased from 1.03 to 0.78. The proportion of patients experiencing a fall decreased from an average of 5% to 4.08% per quarter, while the proportion of patients experiencing a fall with harm decreased from an average of 1% to 0.75% per quarter. The rate of 30-day readmissions decreased from 10.81% to 4.53% per quarter. Patient satisfaction scores were 1.95 points higher for patients who had medication histories taken by pharmacy than for those who did not (5 versus 3.05).

The complementary utility of cognitive testing and the medication management ability assessment in older adults.

OBJECTIVE: Older adults are susceptible to cognitive declines that may limit independence. Though neuropsychologists opine about risk of functional decline, the degree to which cognitive testing and in-office simulations approximate everyday behavior is unclear. We assessed the complementary utility of cognitive testing and the face-valid Medication Management Ability Assessment (MMAA) to predict medication management among older adults. METHOD: This was a retrospective study of 234 older adults (age = 72 ± 7.7 years; 59% women) who completed the MMAA during outpatient neuropsychological evaluations. Based on comprehensive clinical assessment, most participants (n = 186) were independent in medication management, while 48 received assistance. Demographically adjusted composite scores were derived for attention/processing speed (A/PS), executive functioning (EF), visuospatial/constructional ability (VC), language, and memory domains. Univariate differences in cognition were examined across Assisted versus Independent groups. Logistic regression assessed which cognitive domains independently predicted group status. The incremental value of the MMAA was assessed, holding uniquely associated cognitive test scores constant. RESULTS: Those receiving assistance with medication management performed worse across all neurocognitive domains and the MMAA compared with independent counterparts. EF was the only unique cognitive predictor of medication management status. When modeled alone, EF and MMAA performance correctly classified 79.5% and 80.8% of cases, respectively. When modeled together, both were independently associated with medication management status and correctly classified 83.3% of cases. CONCLUSIONS: EF uniquely predicted medication management status beyond other cognitive domains. The MMAA provided complementary predictive utility. Concurrent interpretation of executive functioning and MMAA performance is advised when assessing older adults suspected of medication mismanagement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Remission and Treatment Augmentation of Depression in the United States.

Objective: To determine the proportion of adults treated for depression in the US who achieve remission and, among those not achieving remission, the proportion receiving augmentation treatment.Methods: Using data from the US National Health and Nutrition Examination Survey (NHANES) for years 2013-2014, 2015-2016, and 2017-2018, we identified 869 adults who reported using antidepressant medications for depression for at least 3 months. This sample was partitioned into remitted (score < 5) and non-remitted (score ≥ 5) respondents based on 9-item Patient Health Questionnaire (PHQ-9) score-a questionnaire based on the DSM-IV criteria for major depressive disorder. Among the non-remitted group, the proportion receiving antidepressant augmentation with another antidepressant medication of a different class or other medications was also assessed.Results: An estimated 43.5% of adults receiving antidepressant medications for depression were in remission when assessed. Among those not in remission, 28.1% were using augmentation treatment, which in most cases was another antidepressant medication from a different class. As compared to depressed adults without any mental health contact in the past year, those with such contact had significantly higher odds of using augmentation treatment (adjusted odds ratio = 2.72; 95% CI, 1.56-4.76; P = .001).Conclusions: The low percentage of US adults treated with antidepressants for depression that achieves remission represents a missed clinical and public health opportunity to optimize depression treatment. Closer monitoring of symptoms through measurement-based care and setting symptom remission as a goal can help improve outcomes for adults with depression.

Efficacy of systemic therapies in men with metastatic castration resistant prostate cancer harboring germline ATM versus BRCA2 mutations.

BACKGROUND: Among men with metastatic prostate cancer, about 10% have germline alterations in DNA damage response genes. Most studies have examined BRCA2 alone or an aggregate of BRCA1/2 and ATM. Emerging data suggest that ATM mutations may have distinct biology and warrant individual evaluation. The objective of this study is to determine whether response to prostate cancer systemic therapies differs between men with germline mutations in ATM (gATM) and BRCA2 (gBRCA2). METHODS: This is an international multicenter retrospective matched cohort study of men with prostate cancer harboring gATM or gBRCA2. PSA50 response (≥50% decline in prostate-specific antigen) was compared using Fisher's exact test. RESULTS AND LIMITATIONS: The study included 45 gATM and 45 gBRCA2 patients, matched on stage and year of germline testing. Patients with gATM and gBRCA2 had similar age, Gleason grade, and PSA at diagnosis. We did not observe differences in PSA50 responses to abiraterone, enzalutamide, or docetaxel in metastatic castration resistant prostate cancer between the two groups; however, 0/7 with gATM and 12/14 with gBRCA2 achieved PSA50 response to PARPi (p < .001). Median (95% confidence interval) overall survival from diagnosis to death was 10.9 years (9.5-not reached) versus 9.9 years (7.1-not reached, p = .07) for the gATM and gBRCA2 cohorts, respectively. Limitations include the retrospective design and lack of mutation zygosity data. CONCLUSIONS: Conventional therapies can be effective in gATM carriers and should be considered before PARPi, which shows limited efficacy in this group. Men with gATM mutations warrant prioritization for novel treatment strategies.

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment. METHOD: From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AE). RESULTS: Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65-0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85-1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69-1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72-1.05, P = .15) was found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35-1.97, P < .00001). CONCLUSIONS: PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.

Detrimental effect of antiepileptic drugs dose in pediatric children with epilepsy in Saudi Arabia: A prospective cohort study.

ABSTRACT: This study aims to evaluate the effect of dose titration for different oral antiepileptic medications among children with epilepsy in Riyadh, Saudi Arabia.A single-center prospective pilot, cohort study was undertaken at a tertiary hospital in Riyadh, Saudi Arabia. All medical records of pediatric patients below the age of 14 years of age who has been newly diagnosed with epilepsy by attending a medical specialist or on a new epileptic treatment plans were enrolled in the study.A total of 76 epileptic patients were screened for 3 months' period and 48 patients were included in this study. Out of the 48 patients, 31 patients followed the regular practice in the titration processes and 17 patients were in the British national formulary (BNF) guideline. Fifteen children who were on monotherapy of levetiracetam were in regular practice guideline experienced poor seizure control with a recorded number of seizure incidence (n = 10). The patient in regular practice guidelines using a combination therapy of phenytoin and levetiracetam were experiencing some behavioral disturbance and sedation effect. Seventeen patients followed in the BNF guideline who were on levetiracetam were experienced less adverse effect (n = 2) with no behavioral changes.The group who followed the regular practice found having a greater incidence of documented adverse effects compared to the patients following the BNF guideline. The titrating antiepileptic medication has a detrimental effect on the pediatric population as observed in this study.

Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care.

OBJECTIVE: To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF). METHODS: We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects. RESULTS: 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI. CONCLUSION: ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

Trajectories of disease courses in the inception cohort of newly diagnosed patients with JIA (ICON-JIA): the potential of serum biomarkers at baseline.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging. METHODS: We analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later. RESULTS: Two-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months. CONCLUSION: Our data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.

Challenges in Chronic Genetic Disorders: Lessons From the COVID-19 Pandemic.

To examine the impact of the COVID-19 pandemic, we interviewed 26 patients with lysosomal storage disorders receiving enzyme replacement therapy. 20 (77 %) had significant interruption in their treatment, with an average of 8 (range 2-28) missed doses. Alternate methods of delivering uninterrupted care including home therapy were used. Vulnerable patients with chronic genetic disorders require organization for their multidisciplinary needs of care.

The Impact of Antipsychotic Formulations on Time to Medication Discontinuation in Patients with Schizophrenia: A Dutch Registry-Based Retrospective Cohort Study.

BACKGROUND: Many patients with schizophrenia discontinue antipsychotic medication, frequently with adverse outcomes. Although different antipsychotic formulations are associated with different times to discontinuation, not much is known about discontinuation rates with oral-weekly formulations. Such a formulation of penfluridol is available in both the Netherlands and several other countries. OBJECTIVES: We aimed to investigate the impact of antipsychotic formulations on time to discontinuation, especially the oral-weekly formulation. METHODS: In a large, registry-based, retrospective cohort study from 1 January 2013 to 31 December 2016, we determined the time to medication discontinuation during the follow-up period with antipsychotic formulations, including oral-daily, oral-weekly, depot, or a combination of these. Patients with schizophrenia aged between 18 and 69 years were included and stratified according to the duration of recent antipsychotic use (taking the same formulation for ≤ 60 days or > 60 days before follow-up: short-term or long-term recent antipsychotic use). Medication discontinuation was defined as discontinuation of current antipsychotic formulation. RESULTS: Overall, 8257 patients were included for analyses, with 80% of patients discontinuing antipsychotic medication. Time to discontinuation was longer in those with long-term recent antipsychotic use before the follow-up period and longest for oral-daily formulations. Patterns for discontinuation of oral-weekly and depot formulations were similar, regardless of the duration of recent antipsychotic use before follow-up. More prior discontinuations were associated with shorter time to discontinuation. CONCLUSIONS: Time to discontinuation differed considerably between formulations. The duration of recent antipsychotic use was a strong predictor of time to discontinuation. While oral-daily formulations had the longest time to discontinuation in the long-term recent antipsychotic use group, discontinuation trends were similar for oral-weekly and depot formulations. An oral-weekly formulation, whose administration route is noninvasive, might therefore be considered an alternative to depot formulations.

Preoperative Management of Endocrine, Hormonal, and Urologic Medications: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement.

Perioperative medical management is challenging due to the rising complexity of patients presenting for surgical procedures. A key part of preoperative optimization is appropriate management of long-term medications, yet guidelines and consensus statements for perioperative medication management are lacking. Available resources utilize the recommendations derived from individual studies and do not include a multidisciplinary focus or formal consensus. The Society for Perioperative Assessment and Quality Improvement (SPAQI) identified a lack of authoritative clinical guidance as an opportunity to utilize its multidisciplinary membership to improve evidence-based perioperative care. SPAQI seeks to provide guidance on perioperative medication management that synthesizes available literature with expert consensus. The aim of this Consensus Statement is to provide practical guidance on the preoperative management of endocrine, hormonal, and urologic medications. A panel of experts with anesthesiology, perioperative medicine, hospital medicine, general internal medicine, and medical specialty experience was drawn together and identified the common medications in each of these categories. The authors then utilized a modified Delphi approach to critically review the literature and generate consensus recommendations.

Impact of Therapeutic Inertia on Long-Term Blood Pressure Control: A Monte Carlo Simulation Study.

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Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.

Absorption, Metabolism, Distribution, and Excretion of Letermovir.

BACKGROUND: Letermovir is approved for prophylaxis of cytomegalovirus infection and disease in cytomegalovirus-seropositive hematopoietic stem-cell transplant (HSCT) recipients. OBJECTIVE: HSCT recipients are required to take many drugs concomitantly. The pharmacokinetics, absorption, distribution, metabolism, and excretion of letermovir and its potential to inhibit metabolizing enzymes and transporters in vitro were investigated to inform on the potential for drug-drug interactions (DDIs). METHODS: A combination of in vitro and in vivo studies described the absorption, distribution, metabolism, and routes of elimination of letermovir, as well as the enzymes and transporters involved in these processes. The effect of letermovir to inhibit and induce metabolizing enzymes and transporters was evaluated in vitro and its victim and perpetrator DDI potentials were predicted by applying the regulatory guidance for DDI assessment. RESULTS: Letermovir was a substrate of CYP3A4/5 and UGT1A1/3 in vitro. Letermovir showed concentration- dependent uptake into organic anionic transporting polypeptide (OATP)1B1/3-transfected cells and was a substrate of P-glycoprotein (P-gp). In a human ADME study, letermovir was primarily recovered as unchanged drug and minor amounts of a direct glucuronide in feces. Based on the metabolic pathway profiling of letermovir, there were few oxidative metabolites in human matrix. Letermovir inhibited CYP2B6, CYP2C8, CYP3A, and UGT1A1 in vitro, and induced CYP3A4 and CYP2B6 in hepatocytes. Letermovir also inhibited OATP1B1/3, OATP2B1, OAT3, OCT2, BCRP, BSEP, and P-gp. CONCLUSION: The body of work presented in this manuscript informed on the potential for DDIs when letermovir is administered both intravenously and orally in HSCT recipients.