The prospective economic impact of once monthly paliperidone palmitate versus oral atypical antipsychotics in Medicaid patients with schizophrenia

Objectives: Multiple real-world studies have reported potential cost savings associated with second-generation antipsychotic long-acting injectable therapies (SGA-LAIs), including once monthly paliperidone palmitate (PP1M). Yet, only about 12% of Medicaid patients with schizophrenia initiate SGA-LAIs, with poor adherence contributing to frequent relapse among patients on oral atypical antipsychotics (OAAs). The objective of this study was to project the economic impact when an incremental proportion of non-adherent patients with a recent relapse switched from OAAs to PP1M.

Methods: A 12?month decision-tree model was developed from a Medicaid payers’ perspective. The target population was non-adherent OAA patients with a recent relapse. At equal adherence, risk of relapse was equal between PP1M and OAAs, and OAA patients remained non-adherent until treatment switch. Outcomes included number of relapses, relapse costs and pharmacy costs.

Results: Based on a hypothetical health plan of 1 million members, 3037 schizophrenia patients were non-adherent on OAAs with a recent relapse. Compared to continuing OAAs, switching 5% of patients (n?=?152) to PP1M resulted in net schizophrenia-related cost savings of $674,975 at a plan level, $4445 per patient switched per year and $0.0562 per member per month, with a total of 92 avoided relapses over 12?months. Total annual plan level schizophrenia-related costs were $114.1?M when all patients switched to PP1M before any subsequent relapse (n?=?3037), $123.4?M when patients switched to PP1M after a first subsequent relapse (n?=?2631), and $127.6?M when all patients continued OAAs. Switching all patients to PP1M before any subsequent relapse averted 917 relapses, at a lower cost per patient switched ($37,559) compared to switching after a first subsequent relapse ($45,089) or continuing OAAs ($42,005).

Conclusion: Over 12?months, pharmacy costs associated with switching patients from OAAs to PP1M were offset by reduced relapse rates and schizophrenia-related healthcare expenditures, with earlier use of PP1M projected to generate greater cost savings.     

Oral antineoplastic agents: assessment of safety and dose adjustments in clinical practice

Objectives: Although the safety profile of oral antineoplastic agents (OAAs) is better than that of classic chemotherapy, the rate of severe adverse events (AEs) is high. The objective was to assess the reasons for adjustments to treatment with OAAs during the first 100 days of treatment.

Methods: The authors performed a prospective observational study of cancer outpatients who initiated OAAs between November 2015 and October 2017. Dose reductions and treatment interruptions were closely followed-up during the first 100 days after the beginning of treatment with an OAA. The authors described the different safety profile of different OAA classes.

Results: The authors included 443 patients (31 different OAA assessed), of whom 53.0% required their OAA to be adjusted during the first 100 days of treatment. A total of 151 patients required dose reductions and/or interruptions of OAAs owing to AEs. The authors identified 203 AEs in these patients. Treatment with sorafenib, lower ECOG performance status, and first-line treatment were associated with a higher proportion of treatment adjustments due to AEs.

Conclusion: These results in clinical practice could be a first approach to help healthcare professionals to design patient monitoring programs by identifying priority patients and drugs, and remarks the importance of pharmacovigilance in OAAs.     

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.     

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.     

Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data

Objective: Early initiation of antipsychotic treatment in schizophrenia is associated with improved outcomes. This study aimed to determine if initiation of long-acting injectable (LAI) antipsychotic treatment early in a new schizophrenia episode is associated with lower hospitalization rates and healthcare costs in a real-world setting.

Methods: This retrospective (January 1, 2007–June 30, 2016) cohort analysis used claims from Truven Health Analytics MarketScan Commercial, Medicaid, and Medicare Supplemental databases. In adults ≥18?years with a new episode of schizophrenia, two mutually exclusive cohorts were identified based on time from first recorded schizophrenia diagnosis date to first date of LAI initiation (index date): ≤1?year (early initiators) and >1?year (late initiators). Logistic and general linear regression models were performed to estimate adjusted hospitalization rate and healthcare costs in a 1-year follow-up, controlling patient demographic and clinical characteristics, insurance type, baseline all-cause hospitalizations and ED visits, and baseline psychiatric medication use.

Results: Of the subjects, 32% (n?=?1388) initiated treatment early and 68% (n?=?2978) initiated treatment later. In risk-adjusted models, all-cause hospitalization rates were 22.2% (95% CI?=?19.9–24.6%) in early initiators and 26.9% (95% CI?=?25.2–28.7%) in late initiators (p?=?.002). Of early initiators, 14.1% (95% CI?=?12.3–16.1%) had a psychiatric hospitalization vs 19.2% (95% CI?=?17.7–20.8%) of late initiators (p?<?.001). Adjusted psychiatric healthcare costs were significantly lower in early initiators compared with late initiators [mean (95% CI)?=?$21,545 (20,355–22,734) vs $24,132 (23,330–24,933)] (p?<?.001).

Conclusions: LAI initiation within 1 year of a new schizophrenia episode led to lower hospitalization rates and healthcare costs compared with LAI initiation more than 1 year after a new episode.     

Mortality,length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common and life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The extent to which aGVHD increases inpatient costs associated with allo-HSCT has not been thoroughly evaluated. In this analysis, mortality, hospital length of stay (LOS) and costs associated with aGVHD during allo-HSCT admissions are evaluated.

Methods: This is a retrospective analysis of discharge records from the National Inpatient Sample database for patients receiving allo-HSCT between 1 January 2009 and 31 December 2013. Allo-HSCT discharges with an aGVHD diagnosis were included in the aGVHD group and those without any graft-versus-host disease (GVHD) diagnosis comprised the non-GVHD group. Mortality, LOS and costs were compared between the two groups, as well as within subgroups, including age (<18 vs. ≥18 years) and survival status (alive vs. deceased) at discharge.

Results: Overall, mortality (16.2% vs. 5.3%; p?<?.01), median hospital LOS (42.0 vs. 26.0 days; p?<?.01) and median total costs ($173,144 vs. $98,982; p?<?.01) were significantly increased in patients with aGVHD versus those without GVHD during hospitalizations for allo-HSCT, irrespective of age group. Patients with aGVHD who were <18 years of age had a lower mortality rate but greater hospital LOS and total costs versus patients aged ≥18 years. Patients who died during allo-HSCT hospitalization had longer LOS and incurred greater costs than those who survived in both the aGVHD and non-GVHD groups.

Conclusion: Occurrence of aGVHD during allo-HSCT admissions resulted in a tripling of the mortality rate and a near doubling of hospital LOS and total costs. In addition, death during allo-HSCT hospitalizations was associated with greater healthcare utilization and costs. Effectively mitigating aGVHD may improve survival and substantially reduce hospital LOS and costs for allo-HSCT.     

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.     

Posology adjustments of oral antineoplastic agents for special populations: patients with renal impairment,hepatic impairment and hematologic toxicities

Background: Oral antineoplastic agents (OAA) have reached 30–50% of all antineoplastic treatments. Although they seem safer than parenteral therapy, many severe problems can occur if the dose is not adequately adjusted in special situations. Our objective is to create a comprehensive guide with dosage adjustment recommendations for OAA in cases of renal and hepatic impairment and hematologic toxicities.

Research design and methods: We analyzed all OAA approved by EMA in July 2017. We assessed data related to dose adjusted from the FDA’s and EMA’s summary of product characteristics.

Results: 53 OAA were analyzed. We identified 44 (83%) OAA requiring dosage adjustments in special situations: 20 (37.7%) in renal impairment, 37 (69.8%) in hepatic impairment, and 22 (41.5%) in patients with hematologic toxicity. The dose adjustment recommendations varied in 31 (58.5%) OAA between the FDA and EMA. Detailed recommendations for each OAA were collated into comprehensive tables.

Conclusions: Most OAA have to be adjusted in special situations. Given the number of OAA available for different indications, this review can serve as an easy tool to help health professionals dose these complex treatments.     

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.     

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.     

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.     

Assessment of drug–drug interaction potential and PBPK modeling of CC-223, a potent inhibitor of the mammalian target of rapamycin kinase

1.?CC-223 was studied in vitro for metabolism and drug–drug interactions (DDI), and in clinic for interaction with ketoconazole.

2.?In vitro, human metabolites of CC-223 included O-desmethyl CC-223 (M1), keto (M2), N-oxide (M3) and imine (M13), with M1 being the most prominent metabolite.

3.?CC-223 was metabolized by CYP2C9 and CYP3A, while metabolism of M1 was mediated by CYP2C8 and CYP3A. Ketoconazole increased CC-223 and M1 exposure by 60–70% in healthy volunteers.

4.?CC-223 (IC₅₀?≥?27?µM) and M1 (IC₅₀?≥?46?µM) were inhibitors of CYP2C9 and CYP2C19 in human liver microsomes. CC-223 and M1 were moderate inducers of CYP3A in human hepatocytes.

5.?CC-223 was a substrate of BCRP, and M1 was a substrate of P-gp and BCRP. CC-223 was an inhibitor of P-gp (IC₅₀?=?3.67?µM) and BCRP (IC₅₀?=?11.7?µM), but at a clinically relevant concentration showed no inhibition of other transporters examined. M1 is a weak inhibitor of P-gp and BCRP.

6.?PBPK model of CC-223 and M1 was developed and verified using clinical results. Model based predictions of DDI with ketoconazole were in agreement with observed results enabling prospective predictions of DDIs between CC-223 and CYP3A4 inhibitors.     

Baseline characteristics and treatment patterns of patients with schizophrenia initiated on once-every-three-months paliperidone palmitate in a real-world setting

Objectives: Since May 2015, adult patients with schizophrenia adequately treated with once monthly paliperidone palmitate (PP1M) may be transitioned to once-every-three-months paliperidone palmitate (PP3M). This study aims to describe baseline characteristics and treatment patterns of patients with schizophrenia initiated on PP3M in a real-world setting.

Methods: Pharmacy and medical claims from May 2014 to September 2016 for adult patients with schizophrenia initiated on PP3M (index date) in the Symphony Health Solutions database were analyzed. The cohort consisting of all patients and the one restricted to those transitioning from PP1M as per prescribing guideline recommendations were considered. Baseline characteristics were assessed during the 12 month baseline period. PP1M treatment patterns, proportion of days covered (PDC) by mental-health-related medications, and healthcare resource utilization (HRU) patterns were evaluated for each baseline quarter. PP3M treatment patterns were assessed post-index.

Results: Among the 1545 adult patients initiated on PP3M who formed the first cohort, 68.8% transitioned from PP1M based on prescribing guidelines and on an adaptation of the strict clinical trial protocol for PP1M to PP3M transition, forming the second cohort. In both cohorts, the proportion of patients with a PDC ≥80% for antipsychotics, antidepressants, anxiolytics, and mood stabilizers increased while the proportion of patients with ≥1 emergency room, inpatient, or outpatient visit decreased in baseline quarters closer to PP3M initiation. Among patients with ≥4 months of follow-up after the first dose, 85–88% had a second dose. Similarly, among those with ≥4 months of follow-up after the second dose, 87–90% received a third dose.

Conclusions: Patients initiated on PP3M demonstrated decreased HRU and increased adherence in quarters closer to PP3M initiation, and were persistent on their PP3M treatment.     

‘Isn’t it mostly girls that do pre-drinks really?’ Young men and women’s accounts of pre-loading in the UK

Aims: Pre-loading, the consumption of off-sale alcohol within private settings before socialising in licenced premises, is common among young people. The research explored young people’s accounts of pre-loading within their experience of wider peer group drinking occasions in the UK.

Methods: Fourteen semi-structured focus group interviews were conducted with peer groups of young people (N?=?70, 16–21?years) and analysed using thematic analysis.

Results: Pre-loading with friends prior to a ‘night out’ drinking in public spaces was a common sequential practice within their collective drinking experiences. Although traditionally conceptualised within policy, academic and media discourse as drinking in the domestic sphere before entering licenced premises, young people also considered drinking within the home prior to attending private parties (e.g. house parties) as pre-loading. Price was represented as a key, yet not sole, motivating factor and pre-drinking alcohol held importance in reaching a desired state of intoxication that enhanced shared fun and pleasure among both young men and women. However, the social (e.g. chatting with friends, taking photographs) and preparatory activities (e.g. ‘getting ready’) at play during pre-loading appeared to hold more importance to young women, in promoting group bonding and in the creation and management of heterosexual feminine identities both on- and off-line.

Conclusions: Although price is important, there is a wider social and cultural significance of pre-loading as a gendered phenomenon. Young people apply a wider definition of pre-loading that incorporated the consumption of off-sale alcohol prior to parties within private settings.     

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.     

Secondary cannabis use among London drug treatment service clients

Background: Cannabis is the second most commonly used substance after alcohol among people seeking treatment for other drug use, but no statistics are available regarding secondary cannabis use among drug treatment clients.

Objectives: To investigate levels of secondary cannabis use among drug treatment clients and perceived need for support addressing this use among clients and staff.

Methods: Cross-sectional surveys of clients (N?=?295) and staff (N?=?33) were conducted in 2015 at four London drug and alcohol treatment services. Client measures included recent drug use, type of cannabis used, Severity of Dependence Scale for cannabis, and views on secondary cannabis use treatment. Staff measures included definition of problem cannabis use, importance and timing for addressing secondary cannabis use.

Results: Among clients, 39.7% reported recent secondary cannabis use, with 30.8% of these clients meeting criteria for problem use. Problem users were more likely to be interested in receiving treatment for cannabis use than non-problem users (51.4% versus 10.8%, p?<?.001). Nearly half of staff (48.5%) thought secondary cannabis use should be addressed early in treatment.

Conclusions: Two out of five drug treatment clients used cannabis and a third experienced cannabis-related problems. Many are willing to address cannabis use, but defined treatment pathways are needed.     

Pegvaliase: a novel treatment option for adults with phenylketonuria

Objective: In May 2018, the US Food and Drug Administration approved pegvaliase-pqpz (Palynziq*), the first enzyme substitution therapy for the treatment of phenylketonuria (PKU). This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, and the safety and tolerability profile of pegvaliase.

Methods: Relevant information was identified through a comprehensive literature search of several databases using the keywords pegvaliase, rAvPAL-PEG, and phenylketonuria. Additional information was gathered from the pegvaliase package insert, posters presented at scientific meetings, and materials provided from the manufacturer, BioMarin.

Results: Pegvaliase is effective in decreasing blood phenylalanine levels, and is associated with a manageable side-effect profile. Phase III clinical trial data demonstrated that 60.7% of patients were able to achieve blood phenylalanine levels less than the guideline recommended 360 µmol/L at 24 months. Brief sub-studies also showed the improvement in inattention symptoms in patients treated with pegvaliase, compared to placebo.

Conclusion: Pegvaliase is a promising new treatment option for adults living with PKU. Further studies are warranted to determine long-term safety and clinical efficacy in sub-populations.     

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.     

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.