Continuous Treatment Period Research Articles

7 Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, for Treatment of Patients With WHIM Syndrome: Preliminary Results From Ongoing Open-Label Extension Period of Continuous Mavorixafor Treatment

7 Phase 3 Trial of an Oral CXCR4 Antagonist, Mavorixafor, for Treatment of Patients With WHIM Syndrome: Preliminary Results From Ongoing Open-Label Extension Period of Continuous Mavorixafor Treatment

On-demand Versus Continuous Maintenance Treatment With a Proton Pump Inhibitor for Mild Gastroesophageal Reflux Disease: A Prospective Randomized Multicenter Study.

It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Association of polysubstance use disorder with treatment quality among Medicaid beneficiaries with opioid use disorder

IntroductionThe opioid crisis is transitioning to a polydrug crisis, and individuals with co-occurring substance use disorder (SUDs) often have unique clinical characteristics and contextual barriers that influence treatment needs, engagement in treatment, complexity of treatment planning, and treatment retention. MethodsUsing Medicaid data for 2017–2018 from four states participating in a distributed research network, this retrospective cohort study documents the prevalence of specific types of co-occurring SUD among Medicaid enrollees with an opioid use disorder (OUD) diagnosis, and assesses the extent to which different SUD presentations are associated with differential patterns of MOUD and psychosocial treatments. ResultsWe find that more than half of enrollees with OUD had a co-occurring SUD, and the most prevalent co-occurring SUD was for “other psychoactive substances”, indicated among about one-quarter of enrollees with OUD in each state. We also find some substantial gaps in MOUD treatment receipt and engagement for individuals with OUD and a co-occurring SUD, a group representing more than half of individuals with OUD. In most states, enrollees with OUD and alcohol, cannabis, or amphetamine use disorder are significantly less likely to receive MOUD compared to enrollees with OUD only. In contrast, enrollees with OUD and other psychoactive SUD were significantly more likely to receive MOUD treatment. Conditional on MOUD receipt, enrollees with co-occurring SUDs had 10 % to 50 % lower odds of having a 180-day period of continuous MOUD treatment, an important predictor of better patient outcomes. Associations with concurrent receipt of MOUD and behavioral counseling were mixed across states and varied depending on co-occurring SUD type. ConclusionsOverall, ongoing progress toward increasing access to and quality of evidence-based treatment for OUD requires further efforts to ensure that individuals with co-occurring SUDs are engaged and retained in effective treatment. As the opioid crisis evolves, continued changes in drug use patterns and populations experiencing harms may necessitate new policy approaches that more fully address the complex needs of a growing population of individuals with OUD and other types of SUD.

Association Between Buprenorphine Treatment Gaps, Opioid Overdose, and Health Care Spending in US Medicare Beneficiaries With Opioid Use Disorder

Nonadherence to buprenorphine may increase patient risk of opioid overdose and increase health care spending. Quantifying the impacts of nonadherence can help inform clinician practice and policy. To estimate the association between buprenorphine treatment gaps, opioid overdose, and health care spending. This longitudinal case-control study compared patient opioid overdose and health care spending in buprenorphine-treated months with treatment gap months. Individuals who were US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder who received at least 1 two-week period of continuous buprenorphine treatment between 2010 and 2017 were included. Analysis took place between January 2010 and December 2017. A gap in buprenorphine treatment in a month lasting more than 15 consecutive days. Opioid overdose and total, medical, and drug spending (combined patient out-of-pocket and Medicare spending). Of 34 505 Medicare beneficiaries (17 927 [520%] male; 16 578 [48.1%] female; mean [SD] age, 49.5 [12.7] years; 168 [0.5%] Asian; 2949 [8.5%] Black; 2089 [6.0%] Hispanic; 266 [0.8%] Native American; 28 525 [82.7%] White; 508 [1.5%] other race), 11 524 beneficiaries (33.4%) experienced 1 or more buprenorphine treatment gaps. Treatment gap beneficiaries, compared with nontreatment gap beneficiaries, were more likely to be younger, be male, have a disability, and be Medicaid dual-eligible while less likely to be White, close to a buprenorphine prescriber, and treated with buprenorphine monotherapy (ie, buprenorphine hydrochloride). Beneficiaries were 2.89 (95% CI, 2.20-3.79) times more likely to experience an opioid overdose during buprenorphine treatment gap months compared with treated months. During treatment gap months, spending was $196.41 (95% CI, $110.53-$282.30) more than in treated months. Patients who continued to take buprenorphine dosages of greater than 8 mg/d and 16 mg/d were 2.61 and 2.84 times more likely to overdose in a treatment gap month, respectively, while patients taking buprenorphine dosages of 8 mg/d or less were 3.62 times more likely to overdose in a treatment gap month (maintenance of >16 mg/d: hazard ratio (HR), 2.64 [95% CI, 1.80-3.87]; maintenance of >8 mg/d: HR, 2.84 [95% CI, 2.13-3.78]; maintenance of ≤8 mg/d: HR, 3.62 [95% CI, 1.54-8.50]). Buprenorphine monotherapy was associated with greater risk of overdose and higher spending during treatment gaps months than buprenorphine/naloxone. Medicare patients treated with buprenorphine between 2010 and 2017 had a lower associated opioid overdose risk and spending during treatment months than treatment gap months.

Treatment Patterns During Major Depressive Episodes Among Patients with Major Depressive Disorder: A Retrospective Database Analysis.

BackgroundMajor depressive disorder, a highly prevalent mental health condition, can be challenging to treat.ObjectiveWe aimed to characterize treatment patterns within and across multiple major depressive episodes in patients receiving treatment for major depressive disorder.MethodsAdults with newly diagnosed major depressive disorder and one or more major depressive episodes were identified using the IBM® MarketScan® Commercial database. Eligible patients had 12 months of continuous enrollment before and after diagnosis. Lines of therapy were periods of continuous treatment with one or more antidepressant claims. Antidepressant, atypical antipsychotic, or mood stabilizer regimens as monotherapy or adjunctive therapy were characterized by lines of therapy and major depressive episodes. Descriptive analyses were performed.ResultsA total of 455,082 patients were included in the analysis. The majority of treatment regimens were monotherapy, which decreased with subsequent lines of therapy, while adjunctive treatments increased with subsequent lines of therapy. There were 1860 unique adjunctive regimens identified. Of the 40,315 patients (9%) who received adjunctive therapy, 8024 (20%; 2% of all patients) received atypical antipsychotic-adjunctive regimens. Only 19% of patients treated with atypical antipsychotic-adjunctive therapy discontinued treatment versus 42% of monotherapy-treated patients. On average, patients who received an adjunctive atypical antipsychotic received it as their third line of therapy and approximately 400 days after the initial antidepressant treatment.ConclusionsIn this study, many patients continued monotherapy major depressive disorder regimens and experienced multiple treatment changes. Few patients were treated with adjunctive therapy. These results suggest underutilization of potentially effective treatments, which represents an opportunity to optimize the treatment of patients with major depressive disorder.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00316-4.

Treatment Patterns Among Patients with Bipolar Disorder in the United States: A Retrospective Claims Database Analysis

IntroductionBipolar disorder is a chronic and complex disorder that can be difficult to treat. The objective of this retrospective study was to describe treatment patterns among patients with bipolar disorder.MethodsAdults newly diagnosed with bipolar disorder from 2016 to 2018 were identified using the IBM® MarketScan® Commercial claims database. Patients were enrolled for at least 12 months prior to and 6 months after initial diagnosis. Lines of therapy (LOTs) were continuous treatment periods based on filled prescriptions; medications, such as antidepressants, mood stabilizers, atypical antipsychotics, benzodiazepines, stimulants, and off-label prescriptions, were recorded. All data were analyzed descriptively.ResultsA total of 40,345 patients met criteria. The most common initial episode types were bipolar II (38.1%), and bipolar I depression (29.8%), mania (12.8%), and mixed features (12.0%). Among all episode types, approximately 90% of patients received treatment (LOT1) and approximately 80% of these patients received at least one additional LOT. Across all episode types, the most common medication classes in LOT1 (n = 36,587) were mood stabilizers (43.8%), antidepressants (42.3%; 12.9% as monotherapy), atypical antipsychotics (31.7%), and benzodiazepines (20.7%); with subsequent LOTs, antidepressant (51.4–53.8%) and benzodiazepine (26.9–27.4%) usage increased. Also in LOT1, there were 2067 different regimens. Treatment patterns were generally similar across episode type.ConclusionsAntidepressants and benzodiazepines were frequently prescribed to treat bipolar disorder despite guidelines recommending against use as frontline therapy. These results highlight the considerable heterogeneity in care and suggest that many clinicians treating bipolar disorder are not using evidence-based prescribing practices.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02112-6.

Trial in Progress: A Phase 2, Open-Label Study Evaluating the Safety and Efficacy of the PKR Activator Etavopivat (FT-4202) in Patients with Thalassemia or Sickle Cell Disease

Trial in Progress: A Phase 2, Open-Label Study Evaluating the Safety and Efficacy of the PKR Activator Etavopivat (FT-4202) in Patients with Thalassemia or Sickle Cell Disease

Compliance with Testosterone Replacement Therapy in Patients with Testosterone Deficiency Syndrome: A 10-Year Observational Study in Korea.

PurposeTo determine the compliance rate with testosterone replacement therapy (TRT) in patients with testosterone deficiency syndrome (TDS), we evaluated the treatment continuation rate and the reasons for discontinuation of initial treatment according to each formulations and patient characteristics.Materials and MethodsAmong men over 40 years of age who were diagnosed with TDS and then underwent TRT, their medical records were retrospectively analyzed for those who were followed up for more than 10 years.ResultsA total of 640 patients were included in the analysis. It was found that 75.9% of patients continued treatment for 1 year after starting. Patients treated with 1,000 mg of testosterone undecanoate injection had the highest treatment rate. Inconvenience of medication was the most common reason for discontinuing treatment, followed by cost, concern about side effects, lack of efficacy, and symptom recovery. The reasons for discontinuing treatment differed according to the xlink:type of formulations, and the longest continuous treatment period in all patients was 15.4±7.6 months on average. The treatment continuation rate tended to be high in patients with low serum total testosterone before starting treatment, in patients with severe erectile dysfunction, and in patients using phosphodiesterase-5 (PDE5) inhibitors.ConclusionsAmong the various formulations of TDS, testosterone undecanoate injection (1,000 mg) had the highest compliance rate. In addition, it was found that the reasons for discontinuation of treatment varied according to the characteristics of each formulation.

Factors associated with early and later dropout from methadone maintenance treatment in specialist addiction clinics: a six-year cohort study using proportional hazards frailty models for recurrent treatment episodes

BackgroundRetention in methadone maintenance treatment (MMT) is associated with reduced illicit drug use, criminal activity, and mortality; however, many clients move in and out of MMT. This study aims to identify determinants of time to dropout of MMT across multiple treatment episodes in specialist addiction services in Ireland. MethodsCohort study of persons attending specialist addiction clinics between 2010 and 2015. MMT episodes were periods of continuous treatment if there were no interruptions to treatment lasting > 7days. Proportional hazards frailty models were used to assess factors associated with time to dropout from recurrent MMT episodes at 3 (90 days) and 12 months (91-365 days). MMT episodes were right- censored at time of death, transfer to prison or primary care, and study end. ResultsA total of 2,035 individuals experienced 4,969 MMT episodes, with 2,724 dropout events during the six-year follow-up. Factors associated with dropout at 3 months included low dose methadone (<60 mg/day) (HR = 1.49, 95% CI 1.29-1.73) and previous dropout (HR = 1.65, 95% CI 1.41-1.92). Adherence was protective (HR = 0.91, 95% CI 0.90-0.92). Dropout at 12 months was associated with low dose methadone (HR = 1.44, 95% CI 1.23-1.68), previous dropout (HR = 1.37, 95% CI 1.16-1.61), males (HR 1.26, 95% CI 1.06-1.50), benzodiazepines (HR = 1.22, 95% CI 1.03-1.45) and number of comorbidities (HR = 1.12, 95% CI 1.05-1.20); adherence was protective (HR = 0.86, 95% CI 0.84-0.87). ConclusionsClients with a previous history of treatment dropout and those on low dose methadone should be identified as high risk for both early and later dropout. Inversely, adherence to treatment, not missing methadone doses, is protective.

Cost-Effectiveness Analysis of Sequential Biologic Therapy with Ixekizumab Versus Secukinumab in the Treatment of Active Psoriatic Arthritis with Concomitant Moderate-to-Severe Psoriasis in the UK

BackgroundInterleukin-17A (IL-17A) antagonists are a recent innovation for treating psoriatic arthritis (PsA). There are currently no cost-effectiveness analyses (CEAs) comparing the IL-17A antagonists ixekizumab and secukinumab in PsA from a UK perspective.ObjectiveWe conducted a CEA from the UK National Health Service perspective to compare ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis.MethodsA Markov model was developed based on the widely accepted York model. In biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, ixekizumab → ustekinumab → best supportive care (BSC) was compared with secukinumab → ustekinumab → BSC. For bDMARD-experienced patients, ixekizumab → BSC was compared with secukinumab → BSC. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders continued to receive the bDMARD in the continuous treatment period. PsARC nonresponders and patients who ceased continuous treatment transitioned to the trial period of the next treatment.ResultsIxekizumab was less costly and provided more quality-adjusted life-years (QALYs) than secukinumab in bDMARD-naïve and -experienced patients based on list prices, although cost savings and QALY gains were small to modest. In bDMARD-naïve patients, total costs were £155,455 compared with £155,530 for secukinumab (year 2017 values). Total QALYs were 8.127 versus 7.989. In bDMARD-experienced patients, the corresponding values were £140,051 versus £140,264 for total costs and 3.996 versus 3.875 for total QALYs.ConclusionIxekizumab provided more QALYs at a marginally lower cost than secukinumab, and the results were most sensitive to changes in drug costs. Other factors, such as patient preferences for the number of injections and confidential price discounts, may be important considerations in clinical decision-making.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00202-1) contains supplementary material, which is available to authorized users.

Exclusion of Ring-billed Gulls (Larus delawarensis) from recreational beaches using canid harassment

Abstract Ring-billed Gull (Larus delawarensis) populations have dramatically increased throughout their geographic range with the largest concentrations in the Great Lakes region of Canada and the United States. Large populations of gulls cause conflict with humans at recreational beaches, where their effects on human health and safety include bacteria contamination from gull feces. We used border collies to harass and exclude gulls from beaches in summer 2012 and 2013, then measured gull numbers and Escherichia coli. Dogs were effective at reducing gull numbers by 56–76% during continuous and noncontinuous dog treatment periods. Levels of E. coli were lower on dog-treated beaches, but only during the first half of the summer. Mixed modeling analysis showed presence of dogs was a strong predictor of gull numbers and E. coli levels, with variation among dogs, possibly related to age. Noncontinuous use of dogs, applied within an integrated beach management framework, can provide a nonlethal method for reducing gull use and E. coli levels at recreational beaches.

Trajectories of patients with severe mental illness in two-year contact with Flexible Assertive Community Treatment teams using Routine Outcome Monitoring data: An observational study.

ObjectiveUsing outcome data collected routinely over a continuous two-year treatment period, we wished to distinguish homogeneous subgroups of patients with a severe mental illness whose psychosocial problems followed a similar pattern over time. By identifying the effectiveness of health services for different patient groups, this approach allowed us to identify patients at risk of deterioration and those recovering from their symptoms.MethodsIn total we included 2,660 patients who were in two-year continuous contact with a Flexible Assertive Community Treatment team (FACT). We collected outcome data on psychosocial functioning, needs for care and quality of life. We performed a latent class growth analysis (LCGA).ResultsThe LCGA identified six homogenous patient subgroups using trajectories of HoNOS scores. On the basis of the patterns of patients’ psychosocial problems over time, we labelled these as follows: 1) stable at a low problem-severity level (N = 709; 27%); 2) stable at a low medium problem-severity level (N = 1,208; 45%); 3) stable at a high medium problem-severity level (N = 528; 20%); 4) stable at a high problem-severity level (N = 116; 4%); 5) amelioration of problems (N = 42; 2%); and 6) deterioration of problems (N = 57; 2%). Patients with stable and a high severity of psychosocial problems had more practical and somatic unmet needs than those in other subgroups, and also had the fewest decrease in the number of unmet needs.DiscussionAfter linking patient subgroups with clinical features such as the need for care, we found that, over two years, most patients remained relatively stable in terms of psychosocial functioning, but that their unmet needs decreased over time. However, in terms of needs for treatment during two years of contact with a FACT team, patients in the subgroup with a stable and high problem-severity level tended to derive little or no benefit.

Differentially Enhancing Effects of Long-term Treatment with Serrazyme, Boswellia and Pine on Seminal Bacterial Detection in Patients with Chronic Bacterial or Inflammatory Prostatitis, Probably Related to Several Degrees of Bacterial Adherence.

Prostatitis is a recurrent urinary infection in males and is often difficult to cure. The aim of the study was to examine whether anti-inflammatory effects of enhanced drainage of prostatic secretions, obtained through two months treatment with a proteolytic enzyme mucoactive (PEM) compound (Serrazyme and other constituents), influenced qualitative or quantitative expressions of bacterial growth in seminal cultures. 450 patients with prostatitis syndromes were randomized either to PEM therapy (intervention group) or to no treatment group. All patients were followed at the end of a 2-month PEM continuous treatment period (T2) and further two months after withdrawal (T4). After treatment, 15 out of 107 (14.1%) patients with Chronic Bacterial Prostatitis (CBP) showed negative seminal cultures, while in patients with cat NIH-IIIA prostatitis seminal cultures became positive in 33.3% cases with low bacteriospermia. After two months from withdrawal, although among CBP patients the total number of isolates and colony forming units (CFU) counts showed not significant changes compared to matched-values observed at T2, microbial parameters varied significantly among inflammatory prostatitis patients. The results of the present study showed that 2 months of treatment with PEM, decreasing bacterial adherence and inflammatory prostatitis, reveals a subgroup of apparent inflammation associated with infection that microbial biofilms likely mask in inflammatory prostatitis patients.

Abstract 2840: Characterization of pazopanib resistance in renal cell carcinoma cell lines

Abstract BACKGROUND: Together with Sunitinib (Sun), Pazopanib (Paz) is considered as a gold standard in metastatic renal cell carcinoma treatment (RCC). Similarly to other tyrosine kinase inhibitors (TKI), development of resistance constitutes the main problem of Paz-based therapy. This warrants the in vivo investigations of the processes related to Paz resistance development. METHODS: Parental human RCC cell lines, 786-O/wt and CAKI-2/wt, were continuously treated with Paz at IC50 concentration and Paz-resistant 786-O and CAKI-2 cell subpopulations (786-O/res and CAKI-2/res) were developed. Parental and resistant cells were compared in terms of the malignant phenotype by WST-1 proliferation, cross-resistance to another TKI, migration wound healing assays and signaling pathways analysis by Western blot. MiRNA expression was analyzed using microarrays (Agilent Technologies). RESULTS: The in vitro analysis of RCC cells growth under Paz treatment revealed that this drug inhibited proliferation of parental 786-O and CAKI-2 cells with IC50 (inhibitory concentration of 50%) of 14 and 11 µmol/L, respectively. The continuous treatment with this drug resulted in the gradual resistance development in both tested cell lines. At the end of the period of continuous treatment (32 passages, 3 months) the resistance level of 786-O/res and CAKI-2/res cells was increased 2-fold compared with 786-O/wt and CAKI-2/wt. The analysis of cell motility revealed that the short-termed exposure to Paz retarded the migration of both parental and Paz-resistant 786-O and CAKI-2 cells. However, no differences in the motility rates of parental and resistant cells were observed. The analysis of the signaling pathways that might be involved in the resistance development revealed no changes in the expression of epithelial-to-mesenchymal transition (EMT) markers N-cadherin, vimentin and β-catenin between parental and Paz-resistant subpopulations of both cell lines. Cell response to Paz treatment differs between the tested parental RCC cell lines CAKI-2 and 786-O in terms of the expression of phosphorylated forms of the growth-promoting molecules of Akt-mTOR and MAPK-ERK pathways. A significant change in miRNA expression was found in both cell lines at different time points of treatment compared to parenteral cells. CONCLUSIONS: Our data suggest that the process of Paz resistance development is cell line specific. Akt-mTOR and MAPK-ERK signaling pathways seem to be related to Paz resistance development in RCC. Development of resistance is associated with specific miRNA alterations. Further studies have to analyze the functional effects of miRNAs on resistance and possible signaling pathways. Citation Format: Bozhena Vynnytska-Myronovska, Joana Heinzelmann, Sebastian Hölters, Michael Stoeckle, Kerstin Junker. Characterization of pazopanib resistance in renal cell carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2840.

O7.2. BREAKTHROUGH ON ANTIPSYCHOTIC MAINTENANCE MEDICATION IN A CLINICAL COHORT

BackgroundAntipsychotic drugs are effective in reducing the severity of psychotic symptoms both in the short and long term, and in reducing risk of relapse. However, some patients may develop a relapse of their psychotic symptoms despite continued antipsychotic treatment. Arguably, this phenomenon would be best studied in patients treated with long-acting injectable (LAI) formulations, where the dates of exposure can be confirmed, removing the potential confounder of non-adherence. The characterization of this phenomenon can add important knowledge about the intrinsic efficacy of antipsychotic drugs, potential mechanisms involved in the decrement of their efficacy, and the underlying pathophysiology of psychosis that is not modulated via primarily dopaminergic mechanisms. Despite the implications of this clinical phenomenon, research on breakthrough on antipsychotic maintenance medication (BAMM) in models not confounded by non-adherence has been limited. To date, little is known about the incidence and predictors of BAMM in clinical populations.MethodsWe extracted data from a cohort of individuals with a psychotic disorder who were initiated on their first LAI treatment between 2010 and 2015 in the injection clinic at The Zucker Hillside Hospital (New York, USA). We defined BAMM as hospitalization during the period of continuous treatment with LAI, which we used as the primary outcome. LAI treatment was considered continuous for each treatment episode if it was administered following the manufacturer’s recommendations for the first 2 months, and until there was a delay in the administration that would have required additional oral supplementation according to the manufacturer instructions (typically >1.5 times the scheduled interval of administration). We measured the cumulative incidence and time to BAMM in individuals with continuous LAI administration, and conducted univariate and multivariate analyses of covariates.ResultsA total of 291 episodes of continuous treatment were observed. Of those, 44 (15.1%) led to hospitalization despite continuous treatment with a LAI antipsychotic. The median time to hospitalization was 204.5 days. In the multivariate analysis, the number of hospitalizations prior to onset of LAI treatment (5 vs 2, OR=2.75; 95%CI=1.60–4.72) and time since last hospitalization (4 vs 24.8 weeks, OR 0.70; 95%CI=0.53–0.91) were significantly associated with greater odds of hospitalization during continuous antipsychotic treatment. Individuals who were hospitalized despite continuous treatment were more likely to subsequently be treated with clozapine or ECT (18.2% vs 0, OR=4.93; 95%CI=1.25–19.40). We conducted a mutivariate Cox regression analysis for time to hospitalization and a sensitivity analysis comparing BAMM with individuals that completed 2 years of continuous treatment without being hospitalized and the results were consistent.DiscussionIn a clinical cohort, a meaningful proportion of patients with a psychotic disorder treated with LAIs were hospitalized, despite confirmed continuous treatment. The median time to this event occurred about 7 months after onset of LAI treatment, suggesting that these patients had been stable and had reached steady state antipsychotic levels prior to hospitalization. Patients with a more active illness at the time of initiation of LAI treatment were more likely to relapse. These data suggest that more comprehensive investigation of BAMM is feasible; and therefore research focused on this unique group of individuals may provide novel insights into the pathophysiology of psychosis and into the mechanism of action of antipsychotic drugs.

A coupled technique to eliminate overall nonpolar and polar volatile organic compounds from paint production industry

Volatile organic compounds (VOCs) emitted from their manufacturing have a high recycling value but contribute negatively to the environment. Paints as a significant source of VOCs could largely contribute to their emissions. This study employed a pilot scale system for recovery and elimination of highly concentrated VOCs (up to 1.1 × 106 μg m−3) from a paint packaging workshop, which uses the integrated adsorption-cryogenic condensation with photocatalytic oxidation (PCO). Over a 60-day continuous treatment period, average recovery efficiencies of 96.1%, 100%, 97.1% and 98.6% were achieved for aromatic hydrocarbons (AHs), aliphatic hydrocarbons (AlHs), halogenated hydrocarbons (HHs) and oxygenated VOCs (OVOCs), respectively. Data analysis and theoretical calculations confirmed that nonpolar VOCs were preferentially adsorbed, enriched and recycled by activated carbon adsorption (AHs, AlHs and OVOCs > HHs), while residual polar VOCs were subject to subsequent PCO decomposed with average removal efficiency of −10.2% to 79.4%. PCO displayed a higher degradation activity toward polar VOCs (OVOCs > AHs > AlHs). Furthermore, high non-cancer, cancer risks and occupational exposure cancer risks were found as exposed to the emitted VOCs, and a dramatic reduction of the risks were achieved after treatment. This coupled recovery-decontamination techniques illustrated an excellent recoverability to nonpolar VOCs and efficient decomposition activity to polar VOCs, to eliminate almost emitted VOCs, with promising potential application in atmospheric purification and improvement of occupational environments.

Detection of viable but non-culturable legionella in hospital water network following monochloramine disinfection

Prevention of legionellosis remains a critical issue in healthcare settings where monochloramine (MC) disinfection was recently introduced as an alternative to chlorine dioxide in controlling Legionella spp. contamination of the hospital water network. Continuous treatments with low MC doses in some instances have induced a viable but non-culturable state (VBNC) of Legionella spp. To investigate the occurrence of such dormant cells during a long period of continuous MC treatment. Between November 2010 and April 2015, 162 water and biofilm samples were collected and Legionella spp. isolated in accordance with standard procedures. In sampling sites where MC was <1.5mg/L, VBNC cells were investigated by ethidium monoazide bromide (EMA)-real-time polymerase chain reaction (qPCR) and 'resuscitation' test into Acanthamoeba polyphaga CCAP 1501/18. According to the Health Protection Agency protocol, free-living protozoa were researched in 60 five-litre water samples. In all, 136 out of 156 (87.2%) of the samples taken from sites previously positive for L.pneumophila ST269 were negative by culture, but only 47 (34.5%) negative by qPCR. Although no positive results were obtained by EMA-qPCR, four out of 22 samples associated with MC concentration of 1.3±0.5mg/L showed VBNC legionella resuscitation. The presence of the amoeba A.polyphaga in the hospital water network was demonstrated. Our study is the first report evidencing the emergence of VNBC legionella during a long period of continuous MC treatment of a hospital water network, highlighting the importance of keeping an appropriate and uninterrupted MC dosage to ensure the control of legionella colonization in hospital water supplies.

Long-term safety and efficacy of bilastine following up to 12 weeks or 52 weeks of treatment in Japanese patients with allergic rhinitis: Results of an open-label trial

Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR). Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements. Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR. Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

The health risk attenuation by simultaneous elimination of atmospheric VOCs and POPs from an e-waste dismantling workshop by an integrated de-dusting with decontamination technique

This study investigated the simultaneous abatement of atmospheric volatile organic compounds (VOCs) and persistent organic pollutants (POPs), such as polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenyl ethers (PBDEs), using an integrated technique with a bag filter (BF), photocatalysis (PC) and biotrickling filter (BTF) in an electronic waste (e-waste) dismantling workshop. Approximately 3.6×105, 1.1×103, and 2.5×103ngm−3 of VOCs, PAHs, and PBDEs, respectively, were emitted from domestic stoves during a television dismantling process. During 30-day continuous treatment period, the treatment techniques eliminated 83.7%, 87.2% and 94.1% of VOCs, PAHs and PBDEs, respectively. Among three technologies, PC was responsible for the removal of 78.0% of VOCs and 72.3% of PAHs, while the BF technology removed 85.5% of PBDEs. The success assembling of different technologies depended on different gas-particle distributions of PAHs and PBDEs. Meanwhile, the decreased risk indices of all pollutants were also observed. The PC and BF treatment technologies reduced the cancer risks associated with the most VOCs and PBDEs (57.6% and 80.5%, respectively). The BF technology reduced risks from PAHs the most (86.1%), because of much higher toxic equivalency factors associated with particle-related-PAHs. After BTF treatment, the residual organic pollutants were further biodegraded and completely detoxified. This study indicated that the integrated technique, involving both excellent de-dusting and decontamination capabilities, may provide an efficient alternative to current environment purification and human health protection practices.

Effect of application on Adherence Rating Score Scale in treating patients with tuberculosis

To analyze the application effect of Adherence Rating Score (ARS) scale in the treatment of patients with tuberculosis. A total of 1 349 patients with tuberculosis from November of 2013 to May of 2014 in ten counties of Guizhou province were selected. Before treatment, ARS scale was applied. According to data related to the literature on compliance during the follow-up visits in late May and June (the patients were reviewed in late August), correlation of the evaluation score with the actual compliance was analyzed. There were 705 cases with high but 249 cases with low compliance when the ARS score was ≥4, while 213 cases with high compliance and 182 cases with low compliance when the ARS score was <4 in late May. The compliance of cases with ≥4 ARS score was significantly different from those cases with <4 ARS score in May (χ(2)=51.265,P<0.05). 637 cases with high compliance and 317 cases with low compliance when the ARS score was ≥4, and 193 cases with high compliance and 202 cases with low compliance when the ARS score was <4 in June (August), were discovered. The compliance of cases with ≥4 ARS score was significantly different from those cases with <4 ARS score in June ( χ(2)=37.865,P<0.05). Data from the comprehensive analysis, based on May and June (August), showed that there were 543 cases with high compliance and 411 cases with low compliance when the ARS score was ≥4, and 144 cases with high compliance and 251 cases with low compliance when the ARS score was <4 in late May. The compliance of cases with ≥4 ARS score was significantly different from those cases with <4 ARS score (χ(2)=46.802,P<0.05). RESULTS from the regression analysis showed that all of the late May, June (August) and continuous treatment periods were the factors influencing the compliance of the patients (OR=2.448, 95%CI: 1.910-3.138;OR=2.139, 95%CI: 1.678-2.726;OR=2.371, 95% CI: 1.853-3.034). The compliance based on score ARS scale and the actual investigation were significantly related and the compliance could be evaluated using the score ARS scale before the initiation of treatment and could be applied in Guizhou province.