Short-term rehospitalizations in young adults with schizophrenia treated with once-monthly paliperidone palmitate or oral atypical antipsychotics: a retrospective analysis

Objective: To compare rehospitalizations in patients with schizophrenia treated with paliperidone palmitate (PP1M) vs oral atypical antipsychotics (OAAs), with a focus on young adults (18–35 years).

Methods: The Premier Healthcare database (January 2009–December 2016) was used to identify hospitalizations of adults (≥18 years) with schizophrenia treated with PP1M or OAA between September 2009 and October 2016 (index hospitalizations). Rehospitalizations were assessed at 30, 60, and 90 days after each index hospitalization in young adults and in all patients. Proportions of index hospitalizations resulting in rehospitalization were reported and compared between groups using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: A total of 8578 PP1M and 306,252 OAA index hospitalizations were included. Hospitalized young adults treated with PP1M (n?=?3791) were more likely to be seen by a psychiatrist (94.0% vs 90.0%), and had a longer length of stay (12.5 vs 8.6 days) compared to hospitalized young adults treated with OAA (n?=?96,502). Following their discharge, young adults receiving PP1M during an index hospitalization had a 25–27% lower odds of rehospitalization within 30, 60, and 90 days compared to young adults receiving OAAs (all p?<?.001). Similarly, when observing all patients, those receiving PP1M during an index hospitalization had 19–22% lower odds of rehospitalization within 30, 60, and 90 days compared to those receiving OAAs (all p?<?.001).

Conclusions: Following a hospitalization for schizophrenia, PP1M treatment was associated with fewer 90-day rehospitalizations among young adults (18–35 years) relative to OAA treatment. This finding was also observed in other hospitalized adults with schizophrenia.     

Effect of coverage gap on healthcare utilization among Medicare beneficiaries with chronic obstructive pulmonary disorder

Objective: To evaluate the association between the Medicare coverage gap with hospitalization, emergency room (ER) visits, and time to hospitalization in chronic obstructive pulmonary disease (COPD) patients.

Methods: Retrospective cohort study using data from a Medicare Advantage (MA) plan. Patients with ≥1 claim for COPD at baseline, ≥65 years, continuous 24-months enrollment and without any cancer/end stage renal disease diagnosis were eligible. Patients not reaching the coverage gap (no coverage gap) were matched and compared to those reaching the coverage gap and those reaching catastrophic coverage in separate analyses. Chi-square tests and Cox proportional hazards model were used to compare outcomes across matched cohorts.

Results: In total, 3142 COPD patients were identified (79% no coverage gap, 10% coverage gap, and 11% catastrophic coverage). Compared to the no coverage gap group, a larger number of beneficiaries in the coverage gap group had ≥1 hospitalization (26% vs 32%, p?<?.05), ≥ 1 ER visits (43% vs 49%, p?<?.05), and ≥1 hospitalization/ER (total visit) (47% vs 54%, p?<?.05), respectively. Compared to the no coverage gap group, a greater number of beneficiaries in catastrophic coverage had ≥1 ER visit (45% vs 53%, p?<?.05) or ≥1 total visits (48% vs 56%, p?<?.05), respectively. Time to hospitalization was shorter among those entering the coverage gap as compared to the no coverage gap [Hazards Ratio (HR)?=?1.5; p?=?.040].

Conclusions: COPD patients entering the coverage gap and catastrophic coverage were associated with increased utilization of healthcare services. Entering the coverage gap was also associated with shorter time to hospitalization as compared to the no coverage gap.     

Healthcare utilization,medical costs and mortality associated with malnutrition in patients with chronic obstructive pulmonary disease: a matched cohort study

Objective: Although disease-related malnutrition has prognostic implications for patients with chronic obstructive pulmonary disease (COPD), its health-economic impact and clinical burdens are uncertain. We conducted a population-level study to investigate these questions.

Methods: We excerpted data relevant to malnutrition, prolonged mechanical ventilation and medications from claims by 1,197,098 patients which were consistent with COPD and registered by the Taiwan National Health Insurance Administration between 2009 and 2013. These patients were separated into cohorts with or without respiratory failure requiring long-term mechanical ventilation, and each cohort was divided to compare cases who developed malnutrition after their first diagnosis consistent with COPD, versus non-malnourished propensity-score matched controls.

Results: The prevalence of malnutrition was 3.8% overall (10,259/287,000 non-ventilator-dependent; 1198/15,829 ventilator-dependent). Propensity-score matched non-ventilator-dependent patients who became malnourished (N?=?10,242) had comparatively more hospitalizations, emergency room and outpatient visits, longer hospitalization (all p?<?.01), and higher mortality (HR?=?2.26, 95% CI 2.18–2.34) than non-malnourished controls (N?=?40,968). Malnourished ventilator-dependent patients (N?=?1197) had higher rates of hospitalization, emergency room and outpatient visits, but shorter hospitalization (all p?<?.001) and lower mortality (HR?=?0.85, 95% CI 0.80–0.93) than matched non-malnourished controls (N?=?4788). Total medical expenditure on malnourished non-ventilator-dependent COPD patients was 75% higher than controls (p?<?.001), whereas malnourished ventilator-dependent patients had total costs 7% lower than controls (p?<?.001).

Conclusions: Malnourishment among COPD patients who were not dependent on mechanical ventilation was associated with greater healthcare resource utilization and higher aggregate medical costs.     

Pirfenidone improves the survival of patients with idiopathic pulmonary fibrosis hospitalized for acute exacerbation

Objective: To examine the effect of pirfenidone on the survival of patients hospitalized due to acute exacerbation of idiopathic pulmonary fibrosis (AE–IPF).

Methods: The outcomes of 11 consecutive AE–IPF patients who were receiving pirfenidone treatment when they were admitted to a respiratory intensive care unit (RICU) for acute respiratory failure (ARF) (treatment group) were retrospectively compared with those of 9 patients who were not on pirfenidone treatment at admission (control group). The study’s primary outcome measure was survival following RICU admission; the patients’ mortality rate and the length of time spent in the RICU were also assessed.

Results: The treatment group had significantly longer survival than the control group (median survival time: 137.0 [95% CI, 39.0–373.0] versus 16.0 [95% CI, 14.0–22.0] days; p?=?.0009); the hazard ratio for death was 0.2896 (95% CI, 0.09541–0.8791). The treatment group also tended to have a lower RICU mortality rate (3/11 vs. 7/9; p?=?.0698).

Conclusions: Pirfenidone significantly improved survival in IPF patients hospitalized for severe acute exacerbation compared to controls.     

The effect of hospitalization on potentially inappropriate medication use in older adults with chronic kidney disease

Objectives: Potentially inappropriate medication (PIM) use is associated with increased morbidity and mortality in chronic kidney disease (CKD). However, there is a paucity of data on how hospitalization affects PIM use in older adults with CKD. Therefore, we aimed to measure the impact of hospitalization on PIM use in older CKD patients, and identify factors predicting PIM use.

Methods: A retrospective cohort study was conducted in older adults (≥65 years) with CKD admitted to an Australian tertiary care hospital over a 6 month period. PIM use was measured, upon admission and at discharge, using the Medication Appropriateness Index (MAI) and Beers criteria (2015 version) for medications recommended to be avoided in older adults and under certain conditions.

Results: The median age of the 204 patients was 83 years (interquartile range (IQR): 76–87 years) and most were men (61%). Overall, the level of PIM use (MAI) decreased from admission to discharge (median [IQR]: 6 [3–12] to 5 [2–9]; p?<?.01]). More than half of the participants (55%) had at least one PIM per Beers criterion on admission, which was reduced by discharge (48%; p?<?.01). People admitted with a higher number of medications (β 0.72, 95% CI 0.56–0.88) and lower eGFR values (β???0.11, 95% CI ?0.18 to ?0.04) had higher MAI scores after adjusting for age, sex and Charlson’s comorbidity index.

Conclusions: PIMs were commonly used in older CKD patients. Hospitalization was associated with a reduction in PIM use, but there was considerable scope for improvement in these susceptible individuals.     

Real-world outcomes post-transition to once-every-3-months paliperidone palmitate in patients with schizophrenia within US commercial plans

Objectives: To compare comorbidity-related outcomes, adherence to antipsychotics (APs), healthcare resource utilization (HRU), and costs pre- and post-transition to once-every-3-months paliperidone palmitate (PP3M) in commercially-insured patients with schizophrenia.

Methods: Adults with ≥1 claim for PP3M, ≥2 schizophrenia diagnoses, and adequate treatment with once-monthly paliperidone palmitate (PP1M; i.e. no gap of >45?days in PP1M coverage for ≥4?months, same PP1M dosage for the last two PP1M claims, and appropriate PP1M to PP3M dosing conversion) were selected from the IQVIA PharMetrics Plus database (May 2014–February 2018). Generalized estimating equation models adjusted for repeated measurements were used to compare patient characteristics, adherence to APs, HRU, and costs during the 6-month period pre- vs post-transition to PP3M.

Results: Of 152 included patients, the mean age was 41.0?years and 36.2% were females. Post-PP3M transition, patients were less likely to have a claim with a diagnosis for substance-related and addictive disorders (odds ratio [OR]?=?0.57), psychoses (OR?=?0.57), diabetes without chronic complication (OR?=?0.72), and drug abuse (OR?=?0.64; all p?<?.05). Patients were more likely to be adherent to APs (OR?=?2.01, p?=?.007), compared to the period pre-PP3M transition. There was no significant difference in HRU pre- vs post-transition. All-cause total (mean monthly cost difference [MMCD]?=?$242), pre-rebate pharmacy (MMCD?=?$65), and medical costs (MMCD?=?$176) remained similar pre- vs post-transition (all p?>?.05).

Conclusions: Transitioning to PP3M was associated with an improvement in adherence and in comorbidity-related outcomes related to substance-related and addictive disorders, psychoses, diabetes without chronic complication, and drug abuse. These findings suggest PP3M may enhance comorbidity-related outcomes and adherence while remaining cost neutral.     

Hospitalization risk in bipolar disorder patients treated with lurasidone versus other atypical antipsychotics

Objective: This observational study compared the risk of hospitalization for patients with bipolar disorder when treated with lurasidone versus other oral atypical antipsychotics.

Methods: This US commercial claims analysis (4 April 2010 through 24 September 2014) used the Optum Research Database to identify adult patients with bipolar disorder treated with oral atypical antipsychotics (N?=?11,132). The first claim for an atypical antipsychotic defined the index date, with pre-index and post-index periods of 180 and 360 days, respectively. Every month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, no/minimal treatment or other. Starting with the initial month of treatment, the risk of psychiatric or all-cause hospitalization in the subsequent month was examined based on treatment in the current month and pre-index covariates (age, gender, hospitalizations, emergency room visits, diagnoses for anxiety, alcohol abuse, substance abuse, hypertension, type 2 diabetes and obesity) and time-varying versions of the pre-index covariates using a marginal structural model.

Results: After controlling for covariates, relative to lurasidone, the odds of psychiatric and all-cause hospitalization, respectively, were 2–3 times higher for olanzapine (odds ratio [OR]?=?2.78, CI 1.09, 7.08, p?=?.032; OR?=?3.20, CI 1.24, 8.26, p?=?.016), quetiapine (OR?=?2.80, CI 1.13, 6.95, p?=?.026; OR?=?3.23, CI 1.29, 8.11, p?=?.013), risperidone (OR?=?2.50, CI 1.01, 6.21, p?=?.048; OR?=?2.79, CI 1.11, 7.02, p?=?.029), aripiprazole (OR?=?2.13, CI 0.87, 5.20, p?=?.097; OR?=?2.57, CI 1.04, 6.37, p?=?.041) and ziprasidone (OR =2.31, CI 0.91, 5.85, p?=?.079; OR?=?2.49, CI 0.97, 6.40, p?=?.058).

Conclusions: In this claims database analysis, lurasidone-treated patients with bipolar disorder had a significantly lower risk of psychiatric hospitalization compared to quetiapine, olanzapine and risperidone, but not aripiprazole or ziprasidone. Lurasidone-treated patients had a significantly lower risk of all-cause hospitalization compared to quetiapine, olanzapine, risperidone and aripiprazole, but not ziprasidone.     

Examination of burden of skeletal-related events in patients naive to denosumab and intravenous bisphosphonate therapy in bone metastases from solid tumors population

Objectives: Skeletal-related events (SREs), i.e. pathologic fractures, spinal cord compression, surgery and radiation to bone, are serious skeletal complications that occur frequently in patients with bone metastases (BMs) from solid tumors (STs). Clinical guidelines recommend treatment with denosumab and intravenous bisphosphonates (IVBPs) to prevent SREs. However, therapy may be delayed by physicians due to perceived low risk of SREs or for other clinical reasons. This study estimated SRE incidence rates in treatment-naive (i.e. no denosumab or IVBPs) patients with BMs from STs in the US.

Methods: In this retrospective cohort study adult patients with diagnoses of BM and ST between 1 January 2008 and 31 March 2015 were identified from MarketScan Databases. All patients had ≥6 months of data before the first BM diagnosis date (index date) and were followed for ≥6 months from the index date until the earliest of inpatient death, initiation of denosumab/IVBP therapy or end of data. The Kaplan–Meier curve was used to estimate cumulative incidence of SREs. The incremental healthcare cost of SREs was estimated and compared to propensity score matched non-SRE patients.

Results: A total of 47,052 patients met the study criteria. Using the Kaplan–Meier method the cumulative incidences of SREs among treatment-naïve patients were 39.9% (95% confidence internal [CI]: 39.4–40.4), 46.3% (95% CI: 45.8–46.8), 52.5% (95% CI: 51.9–53.2) and 59.4% (95% CI: 58.6–60.3) by month 6, 12, 24 and 48 post index date, respectively. The SRE group was associated with higher all-cause total healthcare cost per-patient-per-year compared to those without SREs ($168,277 vs. $101,020, p < .001).

Conclusions: Almost half (46.3%) of the treatment-naïve population with BMs from STs experience SREs within 1 year of the first BM diagnosis. SREs were associated with an average $67,257 additional healthcare cost annually. Given the high SRE burden in these patients, early initiation of prophylactic therapy should be considered.     

High one-year mortality following hospitalization for severe hypoglycemia among patients with diabetes mellitus: findings of a retrospective cohort study at an acute tertiary care hospital in Singapore

Objectives: Little is known about the 1-year short-term mortality rate following hospital admissions with severe hypoglycemia. This study aimed to determine the factors associated with increased 1-year mortality rate following hospitalization in diabetes patients admitted with severe hypoglycemia to the Singapore General Hospital.

Methods: Clinical, biochemical, and 1-year mortality data from diabetes patients who were admitted with severe hypoglycemia in the year 2014 were extracted from institutional medical records. Patients who passed away during the episode of admissions with severe hypoglycemia were excluded from the analysis. The clinical and biochemical factors between patients who survived and those who did not survive within 1 year following admission were compared using logistic regression analysis.

Results: Three hundred and four patients (181 female and 123 male) were admitted with severe hypoglycemia in 2014, and the mean capillary blood glucose on admission was 2.3?±?0.7?mmol/L. Sixty-three (20.7%) patients died within 1-year post-discharge from the hospital. Compared with patients who survived 1-year post-discharge from the hospital, non-survivors were older (69.3?±?11.0 vs 75.5?±?11.2 years, p?<?.001), had longer lengths of stay (LOS) (5.0?±?7.4 vs 9.0?±?12.8 days, p?=?.02), and had a higher Charlson Comorbidity Index (CCI) (4.1?±?1.9 vs 5.9?±?2.4, p?<?.001). Factors associated with increased 1-year mortality risk were age (odds ratio [OR]?=?1.06; 95% confidence interval [CI]?=?1.03–1.09, p?<?.01), LOS in hospital (OR?=?1.01; 95% CI?=?1.01–1.08, p?<?.01), and CCI (OR?=?1.51; 95% CI?=?1.31–1.75, p?<?.01), respectively.

Conclusions: Older diabetes patients with more comorbidities and longer LOS were at increased risk of dying within a year of discharge after hospitalization with severe hypoglycemia. Admission with severe hypoglycemia has important prognostic implications. Healthcare professionals should address hypoglycemia and other health issues during the hospital admissions.     

Vitamin D deficiency is associated with dyslipidemia: a cross-sectional study in 3788 subjects

Background: Previously we reported on severe vitamin D deficiency in a large-scale cohort in the Tangshan area in northern China. However, whether vitamin D deficiency is associated with cardiovascular risk factors has not been systematically examined in the cohort.

Objective: We aimed to determine the correlation between serum vitamin D status and lipid levels in circulation via an observational study.

Methods: Serum 25-hydroxyvitamin D (25[OH]D) was measured. Based on the measurement subjects were classified into quintiles. Dyslipidemia was defined as having one of the following: elevated serum total cholesterol, LDL cholesterol, triglycerides or decreased HDL cholesterol, under lipid-control treatment.

Results: The study was conducted in a total of 3788 adults in northern China during their routine health examinations. When the highest quintile of the 25(OH)D level was set as reference, the risk of having dyslipidemia increased progressively across the highest to the lowest 25(OH)D with ORs of 1 (reference), 1.232 (95% CI, 1.005–1.509), 1.235 (95% CI, 1.007–1.513), 1.403 (95% CI, 1.143–1.735) and 1.494 (95% CI, 1.217–1.833), respectively (P_trend < .0001) after adjustment for age. This trend was unchanged after further adjustment for several potential confounders. In linear regression analysis, we found an inverse significant correlation between 25(OH)D and triglycerides (β coefficient = ?0.077, p?<?.05) and LDL cholesterol (β coefficient = ?0.245, p < .05), and positive correlation with HDL cholesterol (β coefficient = 0.038, p = .018).

Conclusion: Vitamin D deficiency is found to be associated with dyslipidemia in a cohort of 3788 subjects. Specifically, serum 25(OH)D is inversely correlated with LDL cholesterol and triglycerides levels, and positively correlated with HDL cholesterol level.     

Anti-epileptic drugs associated with fractures in the elderly: a preliminary population-based study

Objective: Although classic anti-epileptic drugs have been associated with increased fracture risk, data are lacking on the outcomes of newer anti-epileptic drugs, such as gabapentin (GBP), levetiracetam, pregabalin, oxcarbazepine (OXC), and topiramate. This study was designed to determine fracture risks in the elderly associated with newly-developed anti-epileptic drugs.

Methods: A total of 2,169 patients (median age = 71.01 years, SD = 11.25 years) who experienced fractures between 2006 and 2013 were selected. For each case, age-, sex-, and comorbidity-matched controls were selected. The assessed clinical outcome was any fracture, and the use of anti-epileptic drugs was used as an exposure variable.

Results: There were no differences in age, sex, or comorbidities between patients and controls, but patients with fractures often lived in urban areas (odds ratio [OR]?=?1.17; 95% confidence interval [CI]?=?1.05–1.29) and had low income (OR = 1.14; 95% CI = 1.01–1.29) compared to controls. A significant increase in fractures was associated with OXC (OR = 3.31; 95% CI = 1.59–6.92), carbamazepine (CBZ; OR = 2.18; 95% CI = 1.31–3.61), and GBP (OR = 1.79; 95% CI = 1.01–3.18). Phenobarbital (OR = 1.97; 95%CI = 0.53–7.34), phenytoin (OR = 0.52; 95% CI = 0.23–1.16), levetiracetam (OR = 1.84; 95% CI = 0.55–6.16), valproic acid (OR = 1.01; 95% CI = 0.53–1.92), lamotrigine (OR = 1.44; 95% CI = 0.12–16.65), and topiramate (OR = 0.47; 95% CI = 0.10–2.31) were not associated with fracture risk.

Conclusions: CBZ, GBP, and OXC users have a significantly higher risk of fracture. Most recently-developed anti-epileptic drugs are not associated with an increased risk of fracture in individuals aged ≥50 years.     

Specific hypertension smartphone application to improve medication adherence in hypertension: a cluster-randomized trial

Introduction: Digital interventions, such as smartphone applications (apps), are becoming an increasingly common way to support medication adherence and self-management in chronic illness.

Aim: To evaluate the effectiveness of the intervention in pharmacological therapeutic adherence in mild to moderate arterial hypertension (AHT), through an app installed on a mobile phone, as well as the degree of control reached by the patient with this tool.

Methods: Prospective, randomized controlled trial, full study and multicenter study. Four primary care centers participated. One hundred and fifty-four hypertensive patients under antihypertensive treatment were included. Two groups were established: a control group (CG) with usual intervention (n?=?77) and an intervention group (n?=?77) (IG), targeting hypertensive people who owned and regularly used a mobile smartphone, specifically using the app called AlerHTA to promote health education and reminder of appointments. There were three visits: initial, 6 and 12 months. Drug adherence was measured by electronic monitors (MEMSs). The primary outcomes were average daily percentage adherence between 80 and 100%, and AHT control.

Results: A total of 148 patients finished the study. Mean age was 57.5?±?9.9. Global adherence was 77.02% (CI?=?70.25–83.79) and daily adherence was 74.32% (CI?=?67.29–81.35%). Daily adherence was 93.15% and 86.3% in IG, and 70.66% and 62.66% in CG after 6 and 12 months respectively (p < .05). The percentage of uncontrolled patients was 28.3% (CI?=?21.05–35.55%). The control of high blood pressure at 12 months was 17.8% and 38.6% for IG and CG respectively (p < .05). The number of patients needed to treat to avoid non-adherence (NNT) was 4.23 patients.

Conclusions: The intervention with an app installed on the mobile phones of hypertensive patients favors pharmacological therapeutic adherence and improves the percentage of hypertensive patient control.

Trial registration: Spanish Agency of Medicine: EPA-SP UN-HTA-2015-01.     

Evaluation of patient support program and adherence to long-acting injectable aripiprazole for patients utilizing injection local care centers

Objective: Patient support programs, such as the ASSURE Program for long-acting injectable aripiprazole, are designed to help support access to medications, including long-acting injectable (LAI) antipsychotics for patients with schizophrenia. This study was conducted to evaluate adherence to long-acting injectable aripiprazole among patients utilizing the program local care centers (LCC).

Methods: Data collected from participating LCC between October 2014 and February 2018 were utilized. Characteristics of patients receiving injections at LCC and participating in additional support services of the program, types of program offering utilized and patient cost share for long-acting injectable aripiprazole were described. Adherence, measured as the proportion of days covered (PDC) during follow-up, was estimated in patients utilizing the LCC for 6 months and 9 months. Patients with PDC ≥80% were considered adherent to treatment.

Results: Two hundred and thirty-four patients received at least one injection at participating LCC and enrolled in the patient support program. Mean (SD) age was 37.3 (13.5) years; 60.7% were male; 32.5% were covered by Medicare. In total, 157 and 87 patients were actively utilizing the LCC for at least 6 months and 9 months, respectively. PDC of 97% and 98% were reported among patients with 6 months and 9 months of follow-up, respectively, and patients were considered adherent to long-acting injectable aripiprazole during follow-up.

Conclusion: Patients utilizing the LCC demonstrated high medication adherence, suggesting that injection services provided by the centers may reduce barriers to treatment and help patients with schizophrenia remain on LAI antipsychotic treatment.     

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.     

Frequency and risk factors for mental disorders following pancreatitis: a nationwide cohort study

Objective: To investigate the frequency and risk factors for mental disorders following pancreatitis.

Methods: Patients with acute pancreatitis (AP) and chronic pancreatitis (CP) were identified (n?=?18,074) from a nationwide database in New Zealand (1998–2015). They were followed from their first hospital admissions for AP or CP to incident mental disorders. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression analyses.

Results: CP (vs AP) was associated with a significantly higher risk of mental disorders (adjusted HR?=?2.00 [95% CI?=?1.53–2.62]). Pre-existing diabetes (adjusted HR?=?8.99 [95% CI?=?6.23–12.96] for AP and adjusted HR?=?3.42 [95% CI?=?2.37–4.96] for CP) and post-pancreatitis diabetes mellitus (adjusted HR?=?7.10 [95% CI?=?4.14–12.19] for AP and adjusted HR?=?2.97 [95% CI?=?1.83–4.82] for CP) were risk factors for mental disorders in individuals following pancreatitis. Severe (adjusted HR?=?2.07 [95% CI?=?1.39–3.06] vs mild) and recurrent (adjusted HR?=?1.62 [95% CI?=?1.07–2.45] vs single episode) attacks were associated with significantly higher risks of mental disorders following AP.

Conclusions: Patients following CP, recurrent AP, severe AP, and those with diabetes are at high risk for developing mental disorders.     

Real-world anaplastic lymphoma kinase (ALK) rearrangement testing patterns,treatment sequences,and survival of ALK inhibitor-treated patients

Background: The anaplastic lymphoma kinase (ALK) treatment landscape is crowded following recent ALK inhibitor approvals, and updated information on real-world treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK rearrangement (ALK+) is needed.

Methods: This retrospective US cohort study used Flatiron Health’s longitudinal electronic health record (EHR)-derived database. Patients (≥ 18 years old) diagnosed with stage IIIB/IV aNSCLC, with documented ALK rearrangement and ≥2 visits after January 1, 2011 were followed until February 28, 2016. Patients enrolled on a clinical trial or exposed to ALK inhibitors other than crizotinib or ceritinib were excluded. Treatment patterns, time and type of biomarker testing, and overall survival (OS) were analyzed.

Results: Median age (n?=?300) was 62.5 years; 55% female; 48% non-smokers; 8.7% central nervous system (CNS) metastases at diagnosis. Overall, 73% and 86% received their first ALK biomarker test before/at diagnosis, or before/during first-line treatment, respectively. In total, 90.0%, 78.1%, and 74.7% received first-, second-, and third-line therapy, respectively. Most patients received ALK-targeted treatment; 62% received crizotinib, of which 21% reported a dose reduction. Progression was the most common reason for crizotinib (78%) and ceritinib (41%) discontinuation. Median OS was 29.4 months (95% CI =24.7–39.6) overall; 27.1 months (95% CI =22.0–35.0) in patients with CNS metastases, and 36.9 months (95% CI =25.1–not reached) without.

Conclusions: Despite widespread crizotinib use in patients with ALK+ aNSCLC, a high proportion of patients progressed. Ongoing analyses of EHR-derived cohorts are valuable in assessing real-world testing rates and therapeutic use of ALK inhibitors.     

Zolpidem high-dose abuse: what about the liver? Results from a series of 107 patients

Objectives: Z-Drugs (ZDs) have been developed to limit benzodiazepines (BZDs) abuse for sleep disorders. Data on the liver toxicity of zolpidem (ZLM) are lacking or anecdotal. The authors evaluated the presence of drug-induced liver injury (DILI) among a cohort of high-dose ZLM abusers.

Methods: Retrospective study analyzing clinical records of 1112 consecutive patients admitted for BZDs detoxification from 2003 to 2018. Inclusion criteria: age >18 y.o.; ZLM abuse/dependence; high-dose ZDs abuse. Exclusion criteria: missing lab data; lack of informed consent. Main outcome was the presence of DILI measured as elevation of ALT/AST levels >250 U/l.

Results: A total of 107 patients met the eligibility criteria. Liver enzymes alterations were present in 9.3% (95% CI 4.6–16.5%); one patient (0.9%, 95% CI 0.0–2.8%) showed DILI criteria. BMI significantly influenced transaminases levels. No correlations between duration nor doses of ZLM abuse and transaminases levels were found.

Conclusion: The present study shows a very low prevalence of DILI among high-dose ZLM abusers. The prevalence of hypertransaminasemia was in line with general population. On one hand ZLM has a substantially safe liver profile but on the other hand ZLM abuse and dependence, especially at very high doses, represents an emerging problem.     

Association between neurodegenerative diseases and pneumonia: a retrospective population-based study

Purpose: The association between pneumonia and neurodegenerative diseases (NDs) has never been reported in detail. We address this relationship with reference to the general population.

Methods: Using Taiwan’s National Health Insurance Research Database to identify a pneumonia cohort (including the typical and atypical), we established an ND cohort of 19,062 patients and a non-ND cohort of 76,227 people. In both cohorts, the risk of pneumonia was measured using multivariable Cox proportional hazards models.

Results: The adjusted hazard ratio (aHR) (95% confidence interval [CI]) for the pneumonia cohort was 2.10 (1.96–2.24), regardless of age, sex, comorbidities or drug use in the ND cohort. The aHR (95% CI) for adults aged 20–49 years was 2.08 (1.58–2.75), men 2.20 (2.01–2.40). However, older subjects were at greatest risk of pneumonia, (3.41 [2.99–3.88]) if the 20–49 years age group is used as the reference. For the ND and non-ND cohorts, those with comorbidities (with the exception of hyperlipidemia) had higher risk; aHR (95% CI) 2.35 (2.30–2.52). The aHR (95% CI) for those without comorbidities is 3.28 (2.52–4.26). No significant difference was observed in incidence of pneumonia between those who were and were not using statin medications; the aHR (95% CI) was 1.03 (0.93–1.14).

Conclusion: The ND cohort had a higher risk of pneumonia, regardless of age, sex, comorbidities or statin use. The risk of pneumonia was higher in elderly and male patients in the ND cohort.     

Assessment of bleeding in chronic liver disease and coagulopathy using the IMPROVE bleeding criteria

Background: In this study, the authors utilized the IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding definition to explore the safety profile of pharmacologic venous thromboembolism (VTE) prophylaxis in patients with chronic liver disease (CLD) and concurrent coagulopathy (INR ≥1.5).

Methods: A retrospective study was conducted on 193 adult patient admissions with a diagnosis of CLD and INR ≥1.5 not due to therapeutic anticoagulation. Patients were stratified based on their receipt of pharmacological thromboprophylaxis or not during hospitalization. The rates of overall bleeding, defined as the composite of major bleeding and clinically relevant non-major bleeding; major bleeding; and clinically relevant non-major bleeding, within 14 days of admission were evaluated. Secondary endpoints included the rates of thrombosis and mortality.

Results: The composite of overall bleeding occurred in 17.6% of the admissions. More patients in the group not receiving pharmacological thromboprophylaxis had overall bleeding (18.5% vs 10%), major bleeding (13.3% vs 10%), and clinically relevant non-major bleeding (14.5% vs 5%), with overlapping 95% CI. When stratified per pharmacological thromboprophylaxis status, IMPROVE bleeding risk score (BRS)?≥?7 was associated with higher rates of overall bleeding, major bleeding, and clinically relevant non-major bleeding as compared to IMPROVE BRS <7, whether patients received or did not receive pharmacological thromboprophylaxis. The overall incidence of in-hospital mortality among our study population was 15.5%. Receiving pharmacological thromboprophylaxis was markedly associated with higher in-hospital mortality (OR?=?16.58, 95% CI?=?4.47–61.45).

Conclusion: This study shows that the IMPROVE BRS calculated on admission may serve as a guide for omission of thromboprophylaxis in advanced CLD.