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.     

Outcomes of spironolactone treatment in patients in Northeast China suffering from heart failure with mid-range ejection fraction

Aim: The treatment effects of spironolactone on heart failure with reduced (HFrEF LVEF <40%) and preserved (HFpEF LVEF ≥50%) ejection fraction are well characterized. It is not clear whether heart failure patients with mid-range ejection fraction (HFmrEF, LVEF 40–49%) benefit from spironolactone. The present study aims to evaluate the efficacy of spironolactone in HFmrEF patients.

Method: This study compared a high dosage of spironolactone (50?mg daily), a low dosage of spironolactone (25?mg daily), and an untreated group for the prevention of major adverse cardiovascular events (MACE) in 279 patients admitted to hospital diagnosed with HFmrEF.

Results: With a mean follow-up duration of 1 year, the death and HF-rehospitalization rate demonstrated significantly lower incidence in those taking spironolactone, compared with the untreated group (21.3% vs 34.5%, p?=?.014, respectively). Further analysis showed no difference between two spironolactone groups (21.8% vs 20.7%, p?=?.861). Kaplan-Meier analysis of outcome-free survival illustrated a significant difference in survival rate among three groups (log-rank testing, p?=?.045). Compared with the baseline level, patients receiving 25?mg spironolactone had a lower physical score (p?<?.05) at 1-year follow-up. MLHFQ total scores in the two spironolactone groups markedly improved compared with the untreated group (p?<?.001); similar results were observed in the MLHFQ physical scores (p?=?.025, .001, respectively) and emotional sub-scale (p?=?.023, .011, respectively); however, paired comparison between the two spironolactone groups showed no difference.

Conclusions: In patients with HFmrEF, treatment with spironolactone significantly reduced the incidence of the primary composite outcomes of all-cause death, and rehospitalization for the management of heart failure compared with placebo, and a high dosage of spironolactone did not show trends of reduction in MACE.     

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients

Aim: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients.

Methods: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR?=?serum albumin/total protein???serum albumin).

Results: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range?=?0.460–3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p?<?.05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p?=?.002) and better PFS (8.0 vs 5.7 months, p?<?.001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p?=?.019, Hazard Ratio (HR)?=?1.380, 95% Confidence Interval (CI)?=?1.055–1.805) and PFS (p?=?.002, HR?=?1.514, 95% CI?=?1.164–1.968).

Conclusion: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.     

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.     

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use,health-related quality of life,safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome

Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP.

Methods: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1?mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS).

Results: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p?=?.0181) or for IBS-D (p?=?.0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported.

Conclusions: Alosetron 1?mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.     

Prescribing patterns and healthcare costs of gout

Objective/methods: The Longitudinal Health Insurance Database (LHID) 2010 was used to identify gout cases and their number of gout flares.

Results: Out of 21,376 gout patients, a total of 3561 (16.7%) had frequent gout flares (≥3 gout flares/year). Average all-cause healthcare utilization (35.9 visits vs. 30.7 visits; p?<?.001) and gout-related utilization (22.7 visits vs. 15.6 visits; p?<?.001) were higher in frequent gout flare patients than in those with infrequent gout flares. The median gout-related cost (USD $369 vs. $285; p?<?.001), but not all-cause costs (p?=?.25), were higher in frequent gout flare patients compared to the infrequent group. Over 55.8% of the flares were treated with colchicine?+?NSAIDs.

Conclusions: In conclusion, patients with frequent gout flares had higher healthcare utilization and gout-related healthcare costs. Colchicine?+?NSAIDs are commonly used therapy for gout flare.     

Comparison of a twice daily injection of insulin aspart 50 with insulin aspart 30 in patients with poorly controlled type 2 diabetes

Objective: To compare the efficacy and safety of a twice daily injection of insulin aspart (BIAsp) 30 and BIAsp50 in patients with type 2 diabetes mellitus (T2DM) poorly controlled with oral hypoglycemic agents (OHAs).

Methods: In this 12 week prospective, randomized, parallel trial, a total of 80 T2DM patients, 59?±?10?years old with a disease duration of 9.3?±?6.6?years and HbA1c >7% despite large doses of metformin and sulfonylurea administration, were randomized to receive BIAsp30 (n?=?40) or BIAsp50 (n?=?40). The primary endpoint was a change in HbA1c at week 12.

Results: The changes in HbA1c from baseline were ?2.5%?±?1.0% in the BIAsp50 group and ?2.5%?±?1.2% in the BIAsp30 group (p?=?.897). No difference was observed in the rate of HbA1c target achievement (<7.0%) between BIAsp50 (42.5%) and BIAsp30 (32.5%) (p?=?.495). The change in fasting plasma glucose (FPG) in the BIAsp50 group was lower than that in the BIAsp30 group (p?<?.001), while the change in two-hour postprandial blood glucose (2hPBG) was higher and blood glucose excursion was lower in the BIAsp50 group than that in the BIAsp30 group (p?<?.001, p?<?.001). A significant improvement in HbA1c was observed with BIAsp50 in subgroups with baseline blood glucose excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L compared with BIAsp30. There were no differences in hypoglycemia or body weight between groups.

Conclusions: Compared with BIAsp30, BIAsp50 showed greater efficacy in patients with baseline BG excursion >7.8?mmol/L or 2hPBG >17.6?mmol/L as well as good safety for hypoglycemia.

Clinical trial registration: ChiCTR-IIR-16008958.     

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter,retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).

Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.

Results: We analyzed 1416 patients (mean age: 53.7?±?14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9?±?3.37 days and 4.2?±?8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48?hours (p?<?.0001), UGIB history (p?=?.0026) and use of anticoagulants (p?<?.0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.

Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.

ClinicalTrials registry number: NCT02316990.     

Comparison of data characterizing the clinical effectiveness of the fluocinolone intravitreal implant (ILUVIEN) in patients with diabetic macular edema from the real world,non-interventional ICE-UK study and the FAME randomized controlled trials

Objective: To compare the effectiveness and safety of the fluocinolone acetonide (FAc) intravitreal implant between the observational Iluvien Clinical Evidence study in the United Kingdom (ICE-UK) and the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) randomized controlled trials (RCTs) in people with diabetic macular edema (DME). Clinical Trials Registration: NCT00344968.

Methods: This study selected patients randomized to receive 0.2?µg/day FAc insert (FAc treated eyes) or sham injection (control eyes) from the FAME RCTs, and patients’ first FAc treated eye and non-FAc treated fellow (control) eye from the ICE-UK study. Outcomes included change in visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP).

Results: After 12 months follow-up, mean change in VA was 5.0 letters improvement (p?<?.001) and 1.6 letters improvement (p?=?.003) in FAME FAc treated and control eyes, and 3.8 letters (p?=?.012) and –2.1 letters (p?=?.056) in ICE-UK FAc treated and control eyes, respectively. Mean change in CFT was –144?µm (p?<?.001) vs –72?µm (p?<?.001) in FAME FAc treated and control eyes and –113 µm (p?<?.001) vs –13?µm (p?<?.001) in ICE-UK FAc treated and control eyes. For eyes with a follow-up of 12 months, 77 (22.3%) and 15 (8.6%) FAME FAc treated and control eyes and 25 (18.7%) and six (4.3%) ICE-UK FAc treated and control eyes required emergent IOP-lowering therapy.

Conclusions: Statistically significant improvements in VA 12 months after FAc implantation were observed in both the real-world study and in the RCTs. The improvement in VA and CFT in the RCTs was marginally greater than in the real-world study; however, recruits in the real-world study had more severe visual morbidity at baseline. Whilst there were many changes in the care of people with DME over this time, these data all support the value of treatment with FAc intravitreal implant.     

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.     

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims

Background: Two recent evaluations reported that many cancer chemotherapy patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle, and that these patients have a higher subsequent risk of febrile neutropenia (FN). Such evidence is based principally on the experience of younger adults with private healthcare coverage, and the generalizability of results to elderly Medicare patients is unknown.

Methods: A matched-cohort design and data from the Medicare Claims Research Identifiable Files were employed. The source population comprised cancer patients aged ≥65 years who received chemotherapy with intermediate/high-risk for FN and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this sub-set, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated using generalized estimating equations.

Results: Among 77,616 elderly patients in the source population, 5.3% did not receive second-cycle PP and were matched to those who did. In cycle 2, FN odds were significantly higher among comparison patients vs PP patients when employing the broad definition (OR?=?1.9, p?<?.001) and the narrow definition (OR?=?2.1, p?<?.001). Results for subsequent cycles (broad definition: OR?=?2.0, p?<?.001; narrow definition: OR?=?2.1, p?<?.001) and for the last cycle (broad definition: OR?=?1.4, p?=?.060; narrow definition: OR?=?1.7, p?=?.055) were largely comparable.

Conclusions: In this large-scale evaluation of elderly Medicare patients who received myelosuppressive chemotherapy and first-cycle PP in recent US clinical practice, FN risk was substantially lower among patients who continued to receive PP in subsequent cycles vs those who discontinued PP.     

Everolimus compliance and persistence among tuberous sclerosis complex patients with renal angiomyolipoma or subependymal giant cell astrocytoma

Objective: Everolimus is the only FDA approved drug to treat renal angiomyolipoma or subependymal giant-cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC). Potential differences exist between patients with commercial and Medicaid insurance on everolimus use; however, there is limited information from the real world. This study compared compliance and persistence of everolimus between commercial and Medicaid patients using US claims data.

Methods: Patients with ≥1 claim of TSC with renal angiomyolipoma or SEGA were selected from the MarketScan commercial (1 January 2009–31 August 2016) and Medicaid (1 January 2009–30 June 2015) databases. Patients were followed from index date (the earliest date of TSC, renal angiomyolipoma or SEGA diagnosis) to death or end of data. Non-persistence, defined as ≥60?day gap without everolimus, and medication possession ratio (MPR) were assessed among the subset of patients with ≥1 year of follow-up from the first everolimus claim.

Results: A total of 1497 TSC patients met the study criteria (896 renal angiomyolipoma only, 411 SEGA only and 190 both). Compared to Medicaid patients (N?=?513), commercial patients (N?=?984) had the same ages (22 years) but a shorter length of follow-up (38 vs. 48 months, p?<?.001). Medicaid and commercial patients had similar rates of being treated with everolimus (14.4% vs. 13.6%, p?=?.668), but it took Medicaid patients a longer time to start everolimus (871 vs. 704 days, p?<?.001). Although the non-persistence rate was not significantly different between commercial and Medicaid patients (42.5% vs. 35.1%, p?=?.561), the number of days from everolimus initiation to non-persistence was significantly lower for commercial patients (945 vs. 1132, p?<?.001). During the 1 year post everolimus initiation, commercial patients had a significantly higher MPR (0.81 vs. 0.74, p?<?.001) and higher percentage of patients with MPR ≥0.80 (67.8% vs. 58.1%, p?<?.001).

Conclusions: Among TSC patients with renal angiomyolipoma or SEGA and treated with everolimus, everolimus MPR was between 0.74 and 0.81. Medicaid patients had lower MPR than commercial patients but better persistence.     

Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients

Objectives: To estimate the real-world (RW) impact of adherence to once-daily (QD: rivaroxaban and edoxaban) and twice-daily (BID: apixaban and dabigatran) non-vitamin K antagonist (NOACs) on the risk of stroke and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients.

Methods: First, claims from the Optum Clinformatics Data Mart database (July 2012–December 2016) were analyzed. Adult NVAF patients with ≥2 NOAC dispensings (index date) were included. The relationship between NOAC adherence (proportion of days covered ≥80%) and stroke/MB 1-year post-index was evaluated using adjusted Cox proportional hazards models. Second, the natural logarithm of hazard ratios (HRs) was multiplied to a literature-derived mean adherence difference between QD and BID NOACs yielding stroke and MB rates. Third, these rates were multiplied by 1-year Kaplan-Meier rates of stroke and MB which yielded the number of strokes prevented and MBs caused. Annual cost savings were evaluated using literature-based stroke ($81,414/patient) and MB ($63,905/patient) cost estimates.

Results: In total, 54,280 patients were included. HRs for adherent vs non-adherent patients were 0.67 (p?<?.001) for stroke and 1.09 (p?=?.179) for MB. The claims-derived 1-year Kaplan-Meier rates were 3.0% and 3.4% for strokes and MBs, respectively. For 100,000?AF patients, 64 strokes were prevented (p?<?.001), and a non-significant number of MBs (n?=?15, p?<?.191) were caused by QD vs BID NOACs annually, which leads to cost savings estimated at $58 million for QD NOACs.

Conclusion: QD NOACs prevented a significant number of strokes and caused no significant increase in MBs compared to BID NOACs, which leads to significant net cost savings for NVAF patients in the US.     

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.     

Altered expression of cyclooxygenase-2, 12-lipoxygenase,inducible nitric oxide synthase-2 and surfactant protein D in lungs of patients with pulmonary injury caused by sulfur mustard

Context: Sulfur mustard (SM) is a strong alkylating toxicant that targets different organs, particularly human lung tissue. Change in genes expression is one of the molecular mechanisms of SM toxicity in damaged tissue.

Objective: The purpose of this investigation is to characterize the expression of cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LO), inducible nitric oxide synthase 2 (iNOS2), and surfactant protein D (SFTPD) in lungs of patients who exposed to SM.

Methods: Lung biopsies were provided from SM-exposed patients (n?=?6) and controls (n?=?5). Total RNA were extracted from all specimens and then cDNA was synthesized for each sample. Changes in gene expression were measured using RT² Profiler ?PCR Array.

Results: Pulmonary function tests revealed more obstructive and restrictive spirometric patterns among patients compared to the control group. Expression of COX-2 and 12-LO in the lung of patients was increased by 6.2555 (p?=?0.004) and 6.2379-folds (p?=?0.002), respectively. In contrast, expression of SF-D and iNOS genes was reduced by 8.5869-fold (p?=?0.005) and 2.4466-folds (p?=?0.011), respectively.

Conclusions: Mustard lungs were associated with overexpression of COX-2 and 12-LO, which are responsible for inflammation, overproduction of free radicals and oxidative stress. Downregulation of iNOS2 and SF-D are probably the reason for lung disease and dysfunction among these patients. Therefore, the expression of these genes could be an important, routine part of the management of such patients.     

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.     

Serum osteocalcin level as an indicator of low-grade albuminuria in Chinese men free of kidney disease

Objective: The presence of low-grade albuminuria (LGA) suggested that the pathophysiology of vascular dysfunction has been initiated. Clear evidence supports a role for osteocalcin in energy metabolism and a great incidence of pathological cardiovascular changes. The observational community-based study aims to examine the association of osteocalcin with LGA, which may provide new insight into potential involvement of osteocalcin in cardiovascular diseases.

Methods: A total of 1951 adults [58.37 (53.34–63.13) years, 41.3% men] from Shanghai were enrolled. LGA was defined as a urinary albumin-to-creatinine ratio (UACR)?<?30?mg/g. Serum osteocalcin was measured using an electrochemiluminescence immunoassay.

Results: Serum osteocalcin level in men decreased with increasing UACR after adjusting for potential covariates (p?=?0.045); however, the adjusted association disappeared in women (p?=?0.258). Linear regression analysis showed that osteocalcin was a negative variable of UACR in men (standardized β =??0.074, p?=?0.030), particularly prominent in non-hyperglycemic, non-hypertensive men, even regardless of estimated glomerular filtration rate (eGFR) (60?≤?eGFR <90?mL/min/1.73 m², standardized β =?0.422, p?=?0.004; ≥ 90?mL/min/1.73 m², standardized β =??0.167, p?=?0.037).

Conclusion: After controlling for confounders, serum osteocalcin level was independently associated with LGA in men, which suggested that osteocalcin was closely related with atherosclerosis and vascular dysfunction.     

A randomized controlled trial comparing tapentadol with oxycodone in non-breastfeeding women post elective cesarean section

Background: Tapentadol may allow greater pain relief with reduced “opioid load” compared to oxycodone. Its use has not been studied in the obstetric population. The objective of this study was to compare the efficacy and side effect profile of tapentadol with oxycodone in patients who received spinal anesthesia for elective cesarean section. The trial was registered with EU Clinical Trials Register with CT number 2016-001621-33.

Methods: This was a multicenter, randomized controlled trial. Randomized patients (n?=?68) received either 50?mg tapentadol or oxycodone 10?mg 12 hourly postoperatively. The primary endpoint was the sum of pain intensity difference over the first 48?hours of treatment (SPID₄₈). Secondary outcomes included time to rescue medications, SPID₃₆, total pain relief (TOTPAR) scores, patient satisfaction scores, sum of total pain relief and pain intensity difference (SPRID) scores, time to rescue medications and side effects experienced. An analysis of covariance model with baseline pain intensity score as a covariate was used for statistical analysis.

Results: There was no significant difference in the primary endpoint of SPID₄₈ with adjusted mean difference -11.45 (95% CI -35.35, 12.45) p?=?.34). Oxycodone showed significantly greater SPID₃₆ scores compared to tapentadol with increased time to rescue medication. Side effects experienced were similar between groups.

Conclusion: Tapentadol did not provide superior pain control or improved tolerability compared to oxycodone post cesarean section. Results should be interpreted however with consideration of administration of intrathecal opioids to all patients in this study and debate over the optimal dose of tapentadol for acute pain.