Routine Clinical Care Setting Research Articles

Effectiveness of ustekinumab in patients with psoriatic arthritis in a real-world, multicenter study.

To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. Two hundred and one patients were included, 130 (64.7%) with 45mg and 71 (35.3%) with 90mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45mg (58.1%) than 90mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and <1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90mg dose.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

Targeting Natriuretic Peptide Levels in Heart Failure with Therapy: Does "X" Really Mark the Spot?

Explore controversial biomarker-guided management of patients with heart failure (HF) with reduced ejection fraction. Natriuretic peptides (e.g., BNP, NT-proBNP) are elevated in HF as a result of end-diastolic stress and are used in the diagnosis and prognosis of heart failure. Natriuretic peptide levels decrease with guideline-directed medical therapy (GDMT). Multiple small studies examined whether the use of biomarker-guided therapy would be beneficial to guide HF care and potentially improve outcomes. Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT), the largest randomized control study seeking to answer that question, did not find biomarker guided therapy to be more effective than usual care in improving the primary endpoints of HF hospitalization or cardiovascular mortality in HF patients. Natriuretic peptides are important for diagnosis and prognosis in HF. GUIDE-IT showed that patients with HF and reduced ejection did not benefit from biomarker-guided strategy in terms of clinical outcomes. Future studies could focus on additional routine clinical care settings and take into account other HF phenotypes including preserved ejection fraction.

Switching to Degludec From Other Basal Insulins Is Associated With Reduced Hypoglycemia Rates: A Prospective Study.

ContextObservational studies of insulin degludec (degludec) with hypoglycemia events prospectively recorded are lacking.ObjectiveTo evaluate the safety and effectiveness of degludec in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) switching from other basal insulins in routine care.DesignResults From Real-World Clinical Treatment With Tresiba® was a multinational, multicenter, prospective, observational, single-arm study comprising a 4-week baseline period (preswitch basal insulin) and 12-month follow-up (degludec).SettingRoutine clinical practice.Patients or Other ParticipantsInsulin-treated patients (≥18 years) with T1D (n = 556) or T2D (n = 611) with treatment plans to initiate degludec.InterventionsSwitching to degludec from other basal insulins.Main Outcome MeasureChange from baseline in number of overall hypoglycemic events recorded in patient diaries.ResultsIn T1D, the 12-month follow-up/baseline rate ratios (95% CI) of overall [0.80 (0.74 to 0.88)], nonsevere [0.83 (0.76 to 0.91)], severe [0.28 (0.14 to 0.56)], and nocturnal [0.61 (0.50 to 0.73)] hypoglycemia suggested significantly lower hypoglycemia rates with degludec (all Ps < 0.001). At 12 months, HbA1c, fasting plasma glucose (FPG), and basal insulin dosage decreased significantly. Body weight increased, and treatment satisfaction improved significantly. In T2D, the hypoglycemia rate ratios were overall [0.46 (0.38 to 0.56)], nonsevere [0.53 (0.44 to 0.64)], and nocturnal [0.35 (0.20 to 0.62)] (all Ps < 0.001; too few events for analysis of severe hypoglycemia). At 12 months, HbA1c and FPG decreased significantly. Body weight and insulin dosages remained unchanged, and treatment satisfaction was significantly improved.ConclusionsIn a routine clinical care setting, switching to degludec from other basal insulins was associated with significantly lower rates of hypoglycemia, improved glycemic control, and treatment satisfaction in patients with T1D or T2D.

Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy

ObjectivesTo assess whether comprehensive genomic profiling (CGP) in the setting of routine clinical care allows molecular classification of recurrent endometrial cancer (EC) into the four Cancer Genome Atlas (TCGA) categories: POLE ultramutated, microsatellite instable, copy-number low, and copy-number high and whether this approach can identify genomic alterations (GAs) which inform treatment decisions. MethodsArchival tissues from 74 patients diagnosed with recurrent EC were prospectively analyzed using hybrid-capture-based genomic profiling. Tumor mutational burden and microsatellite instability were measured. Clinically relevant GAs (CRGAs) were defined as GAs associated with targeted therapies available on-label or in mechanism-driven clinical trials. ResultsUsing POLE mutational analysis, mismatch repair status, and p53 mutational analysis as surrogate for ‘copy-number’ status CGP segregated all cases into four TCGA molecular subgroups. While recurrent serous ECs were predominantly copy-number high, we found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors. Every tumor sample had at least one GA and 91% (67/74) had at least one CRGA. In this series 32% (24/74) of patients received a matched therapy based on the results of CGP. Objective responses to the matched therapy were seen in 25% (6/24) of patients with an additional 37.5% (9/24) achieving stable disease leading to a clinical benefit rate of 62.5% with a median treatment duration of 14.6 months (range 4.3–69 months). ConclusionsCGP allows molecular classification of EC into four TCGA categories and allows identification of potential biomarkers for matched therapy in the setting of routine clinical care.

Psychopharmacological treatment of patients with borderline personality disorder: comparing data from routine clinical care with recommended guidelines

Objectives: Borderline personality disorder (BPD) is a life-threatening mental disorder. Guideline recommendations for pharmacological treatment of patients with BPD vary widely. The objective of the present study was to investigate pharmacotherapy of BPD patients in a routine clinical care setting.Methods: Data on the pharmacological treatment of 110 patients (90% female) with BPD (F- 60.3), treated in an inpatient psychiatric-psychosomatic clinic in Austria were assessed.Results: Results show that clinicians frequently prescribe psychotropic medications to patients with BPD, in many cases multiple medications. The most commonly prescribed substance groups were antipsychotics, mood stabilisers and antidepressants. The most commonly prescribed individual drugs were Quetiapine, Lamotrigine and Setraline. There was no significant difference in the different types or overall number of medications prescribed to BPD patients with vs. without comorbid diagnoses. Pharmacotherapy was not related to comorbidity.Conclusions: The present study shows that in routine clinical care settings psychotropic medications are frequently prescribed to patients with BPD, very often resulting in polypharmacy. A positive association between the number of medications and the effectiveness of the inpatient treatment program, as well as the absence of a relationship between number of medications and comorbidity contradicts the often suggested iatrogenic effect of polypharmacy.Key pointsGuidelines for pharmacotherapy of borderline personality disorders lack consensusYet, clinicians frequently prescribe psychotropic medications to BPD patientsTypes/number of medications prescribed to patients with vs. without comorbidities are similarLarger treatment effects are observed for patients with greater numbers of medicationsFurther knowledge is needed about how and why clinicians prescribe medications

A randomized controlled trial of internet-delivered cognitive behaviour therapy for adolescent anxiety disorders in a routine clinical care setting with and without parent sessions.

Computerized treatments have been shown to be effective in young people with anxiety disorders within research settings. The aims of this study were to evaluate a self-completed, therapist-supported online treatment for adolescent anxiety disorders in a routine clinical care setting and examine whether additional sessions for parents improved treatment outcome. Sixty adolescents (13-18years) referred by primary and secondary care services for treatment of an anxiety disorder and their parent(s) were randomly allocated to begin treatment immediately or after a 16-week waitlist. Half the parents (receiving treatment immediately or after a waitlist) were allocated to receive sessions themselves. Assessments were conducted pre- and posttreatment and at 6-month follow-up. There was no significant difference posttreatment between the immediate treatment and waitlist groups in remission of primary anxiety disorder (Odds Ratio (OR)=2.19, 95% CI: 0.72-6.70). Parent sessions did not significantly improve adolescent outcomes immediately or at 6-month follow-up (OR=0.75, 95% CI: 0.26-2.15; OR=1.14, 95% CI: 0.42-3.15). Within a routine clinical care setting, a therapist-supported online treatment failed to deliver significantly better outcomes for adolescents with anxiety disorders than a waitlist. Further research is needed to develop more effective treatments for this population.

The efficacy of 90-minute versus 60-minute sessions of prolonged exposure for posttraumatic stress disorder: Design of a randomized controlled trial in active duty military personnel.

Posttraumatic stress disorder (PTSD) can have devastating effects on multiple aspects of functioning. Thus, it is imperative to increase access to evidence-based treatment for PTSD. Prolonged Exposure therapy (PE) has extensive empirical support and is one of the first-line PTSD treatments included in civilian, veteran, and military clinical practice guidelines. However, the standard 90-min PE session format can constitute a significant barrier to its adoption in routine clinical care settings, which typically schedule 60-min appointment sessions. If the length of PE sessions could be reduced from 90 to 60 min without compromising treatment efficacy and efficiency, this would remove a major barrier to PE adoption. This paper describes the rationale and methods of a randomized controlled noninferiority trial comparing 90-min versus 60-min PE sessions (including 40- vs. 20-min imaginal exposures, respectively) among 160 active duty military personnel with PTSD. The aims of this study are to: (1) examine the efficacy and efficiency (i.e., rate of symptom improvement) of 90- versus 60-min PE; (2) assess change in psychophysiological markers of treatment response across conditions; and (3) test mechanisms of change underlying the efficacy of PE. The results of this study will inform dissemination efforts in military, veteran, and civilian sectors. Further, identifying mechanisms of therapeutic change will answer important theoretical questions about how PE works, in order to refine and increase the efficacy and efficiency of PE to better meet the needs of individuals with PTSD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Epidemiological characteristics, clinical outcomes and management patterns of metastatic breast cancer patients in routine clinical care settings of Greece: Results from the EMERGE multicenter retrospective chart review study

BackgroundThe “EMERGE” study, aimed to capture real-life management patterns and outcomes in metastatic breast cancer (MBC) in Greece, also accounting for hormone (HR) and human epidermal growth factor receptor 2 (HER2) status.Methods“EMERGE” was a multicenter, retrospective cohort study of adult MBC patients diagnosed between 01-Janaury-2010 and 30-June-2012, either de novo or having progressed from a non-metastatic state. Patient data, including treatment patterns and outcomes, were mainly abstracted through medical chart review.Results386 patients were enrolled by 16 hospital-based oncologists between 12-March-2013 and 31-March-2015. The median look-back period was 29.1 months. At MBC diagnosis, 56.1% of the patients were HR+/HER2−, 16.6% HR+/HER2+, 14.5% HR−/HER2−, and 12.8% HR−/HER2+. In the first line setting, chemotherapy, targeted therapy and endocrine therapy were received by 76.7, 52.4, and 28.3% of the overall population, and by 66.5/36.2/42.0%, 80.4/80.4/28.6%, 88.4/90.7/0.0, and 95.6%/56.5/6.5% of the HR+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2− subpopulations, respectively. In the overall population, the disease progression incidence rate was 0.57 [95% confidence interval (CI): 0.48–0.67] per person-year; median progression-free survival (PFS) was 22.4 (95% CI: 20.4–24.7) and overall survival (OS) was 45.0 (95% CI: 40.9–55.0) months. Median PFS was 24.6 (95% CI: 21.3–27.9) in HR+/HER2−, 19.7 (95% CI: 12.9–25.9) in HR+/HER2+, 23.0 (95% CI: 16.6–29.7) in HR−/HER2+ and 18.3 (95% CI: 10.0–24.7) months in HR−/HER2− subpopulations. A multivariable Cox proportional hazards model, adjusted among other factors for age and duration of diagnosis, HR and HER2 status, demonstrated that in the overall population PFS was better among those receiving first line endocrine therapy (hazard ratio: 0.70; 95%CI: 0.51–0.95; p = 0.024).Conclusions“EMERGE” demonstrates differences between HR/HER2 subtypes in clinical outcomes and divergence from evidence-based guideline recommendations for MBC management, especially as it pertains to the HR+/HER2− patients in which chemotherapy was favored over endocrine therapy in the first line setting.Study registrationThe study has been registered on the electronic Registry of Non-Interventional Studies (RNIS) posted on the website of the Hellenic Association of Pharmaceutical Companies (SFEE): https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=NIS-OGR-XXX-2012/1

Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART): study protocol for a randomized controlled trial

BackgroundThere is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges.We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC).MethodsThe Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is a phase 2, open-label, evaluator-blinded trial involving 120 Ghanaian recent-ischemic-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated 1:1 into either the intervention arm or UC. Patients in the intervention arm will receive Polycap DS® (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. Patients in the UC will receive separate, individual secondary preventive medications prescribed at the physician’s discretion. Both groups will be followed for 12 months to assess changes in carotid intimal thickness regression – a surrogate marker of atherosclerosis – as primary outcome measure. Secondary outcome measures include adherence to therapy, safety and tolerability, health-related quality of life, patient satisfaction, functional status, depression and cognitive dysfunction.DiscussionAn efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, parallel-group, randomized controlled trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in SSA.Trial registrationClinicalTrials.gov, ID: NCT03329599. Registered on 11 February 2017.

Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study

IntroductionRoux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there...

Quality of Life in Patients with β-Thalassemia: Transfusion Dependent Versus Non-Transfusion Dependent

Background: Significant increase in life expectancy has been observed in patients with β-thalassemia in recent years. The improved survival, however, is accompanied by significant ongoing healthcare needs related to the chronic condition; therefore, quality of life (QoL) has emerged as a fundamental focus of comprehensive patient care. We compared QoL outcomes between transfusion-dependent (TD) and non-transfusion-dependent (NTD) patients with β-thalassemia in the routine clinical care setting.Method: Adult patients with β-thalassemia were prospectively enrolled in an observational study in Italy, Greece, Lebanon, and Thailand. All patients completed Short Form 36 Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy (FACT)-Anemia (An) questionnaires at baseline, and then once every 3 weeks using a hand-held electronic device. This analysis evaluated QoL between TD and NTD patients at study entry. Transfusion dependent was defined as receiving ≥ 6 red blood cell (RBC) units in the 24 weeks prior to study entry and no transfusion-free period for ≥ 35 days during that period.Results: A total of 102 patients with β-thalassemia were enrolled, of which 52 were TD and 50 NTD. The mean age of patients was 31.2 years and 70 (68.6%) were females. On average, patients with TD β-thalassemia were 3.6 years younger (P= 0.06) and had moderately higher hemoglobin values at baseline (8.8 vs 8.2 g/dL; P= 0.02). At study entry, all (100%) patients with TD β-thalassemia had received RBC transfusions within the 24 weeks prior to study entry, as per inclusion criteria, versus 5 (10%) patients with NTD β-thalassemia who had received RBC transfusions during the same time period. Patients with NTD β-thalassemia reported lower QoL on all domains and summary scores as captured by the SF-36v2 questionnaire, except for Role-Physical. On average, patients with NTD β-thalassemia experienced statistically significant lower QoL versus their TD counterparts on the domains of General Health (39.5 vs 44.0; P= 0.01), Vitality (49.3 vs 53.7; P= 0.01), and Mental Health (46.8 vs 50.8; P= 0.01), and in the Mental Component Summary Score (46.5 vs 50.8; P= 0.01). Similarly, patients with NTD β-thalassemia reported worse QoL scores from the FACT-An questionnaire on all domains and statistically significant differences were observed for Emotional Well-Being (18.5 vs 20.0; P= 0.02), Functional Well-Being (20.0 vs 23.2; P < 0.01), and FACT-General (82.9 vs 89.4; P= 0.01).Conclusions: In the routine clinical care setting, there are critical unmet medical needs for patients with NTD β-thalassemia as they experience worse QoL on many domains compared with patients with TD β-thalassemia. There is a need for new interventions to treat patients with NTD β-thalassemia and reduce their burden of disease. DisclosuresCappellini:Vifor: Honoraria; Novartis: Speakers Bureau; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau. Kattamis:National and Kapodistrian University of Athens: Employment; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Viprakasit:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Siriraj Hospital: Employment; Shire: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Sutcharitchan:Celgene: Research Funding; Chulalongkorn University: Consultancy, Employment. Mahmoud:Celgene: Employment. Pariseau:Celgene: Employment. Laadem:Celgene: Employment, Equity Ownership. Khan:Nathan S. Kline Institute for Psychiatric Research; Manhattan Psychiatric Center: Employment. Hu:Celgene: Employment, Equity Ownership. Taher:Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.

The Feasibility of Sophisticated Multicriteria Support for Clinical Decisions.

Multicriteria decision-making (MCDM) methods are well-suited to serve as the foundation for clinical decision support systems. To do so, however, they need to be appropriate for use in busy clinical settings. We compared decision-making processes and outcomes of patient-level analyses done with a range of multicriteria methods that vary in ease of use and intensity of decision support, 2 factors that could affect their ease of implementation into practice. We conducted a series of Internet surveys to compare the effects of 5 multicriteria methods that differ in user interface and required user input format on decisions regarding selection of a preferred method for lowering the risk of cardiovascular disease. The study sample consisted of members of an online Internet panel maintained by Fluidsurveys, an Internet survey company. Study outcomes were changes in preferred option, decision confidence, preparation for decision making, the Values Clarification and Decisional Uncertainty subscales of the Decisional Conflict Scale, and method ease of use. The frequency of changes in the preferred option ranged from 9% to 38%, P < 0.001, and rose progressively as the level of decision support provided by the MCDM method increased. The proportion of respondents who rated the method as easy ranged from 57% to 79% and differed significantly among MCDM methods, P = 0.003, but was not consistently related to intensity of decision support or ease of use. Decision support based on MCDM methods is not necessarily limited by decreases in ease of use. This result suggests that it is possible to develop decision support tools using sophisticated multicriteria techniques suitable for use in routine clinical care settings.

Transdiagnostic Clinical Global Impression Scoring for Routine Clinical Settings.

Although there is great interest in the improving the ability to track patients’ change over time in routine clinical care settings, no standardized transdiagnostic measure is currently available for busy clinicians to apply. The Clinical Global Impression (CGI) scales are simple measures widely used as outcomes in psychiatric clinical trials. However, the CGI suffers from poorly defined scoring anchors. Efforts to improve the anchors by enhancing the anchor descriptions have proven useful but are limited by being disease-specific, thereby acting as a barrier to the routine clinical adoption of the CGI. To inform the development of more broadly applicable CGI scoring anchors, we surveyed 24 clinical trial investigators, asking them to rank-order seven elements that inform their CGI-Severity (CGI-S) scoring. Symptom severity emerged as the most important element in determining CGI-S scores; the functional status of the patient emerged as a second element. Less importance was given to self-report symptom scores, staff observations, or side effects. Relative rankings of the elements’ importance did not differ by investigators’ experience nor time usually spent with patients. We integrated these results with published illness-specific CGI anchors to develop the Transdiagnostic CGI (T-CGI), which employs standardized scoring anchors applicable across psychiatric illnesses. Pending validity and reliability evaluations, the T-CGI may prove well-suited for inclusion in routine clinical settings and for incorporation into electronic medical records as a simple and useful measure of treatment efficacy.

Psychopathological and demographic characteristics of hallucinating patients with schizophrenia and schizoaffective disorder: an analysis based on AMDP data.

Hallucinations are at the core of the diagnosis of schizophrenia and schizoaffective disorders, and many neuroscience studies focus on hallucinations. However, there is a lack of data on prevalence, subtyping, and clinical correlates of hallucinations as well as on the comparison of hallucinating schizophrenia versus hallucinating schizoaffective patients. Analysis of all psychopathology evaluations is based on the AMDP scale in a German psychiatric university hospital between 2007 and 2013 regarding patients with schizophrenia or schizoaffective disorder (diagnosed according to ICD-10). Hallucinating versus non-hallucinating patients and age- and gender-matched hallucinating schizophrenic versus schizoaffective patients were compared with regard to key psychopathological and demographic characteristics. Relative to patients with schizoaffective disorder, patients with schizophrenia more often hallucinated at admission (36.6 vs. 16.2%, RR: 2.3, p<0.001). By subtype, frequency of hallucinations ranked auditory verbal>other auditory>visual>somatic/tactile>olfactory/gustatory. Hallucinating patients of either disorder were more often affected with respect to delusions (83 vs. 62% and 81 vs. 48% among patients with schizophrenia and schizoaffective disorder, respectively [both p<0.0001]) and anxiety. Hallucinating patients with schizoaffective disorder did not differ from hallucinating patients with schizophrenia. This is one of the few studies providing data on hallucinations in a routine clinical care setting. Hallucinations are a sign and likely a cause of greater illness severity. Patients with schizoaffective disorder less often experience hallucinations than patients with schizophrenia, but if they do, they seem to resemble patients with schizophrenia with regard to illness severity.

An observational study of inhaled-treprostinil respiratory-related safety in patients with pulmonary arterial hypertension.

Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory-related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory-related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)-approved PAH therapies. This was a long-term, prospective, observational study. All respiratory-related AEs were recorded during the study. The number of PAH patients enrolled was 1,333, 666 treated with inhaled treprostinil and 667 controls (treated with an FDA-approved PAH therapy other than inhaled treprostinil), for a total of 958 and 1,094 patient-years of exposure, respectively. In the inhaled-treprostinil group, 1,281 respiratory-related AEs were reported in 403 patients (61%), and in the control group, 1,295 respiratory-related AEs were reported in 388 patients (58%). Cough, throat irritation, nasal discomfort, and hemoptysis were the most common respiratory-related AEs (occurring in ≥2% of patients in either treatment group) that demonstrated a higher number of events per patient-year of exposure in the inhaled-treprostinil group than in the control group (risk ratio [95% confidence interval]: 1.487 [1.172-1.887], 3.777 [2.050-6.956], 2.039 [1.072-3.879], and 1.957 [1.024-3.741], respectively). Overall, inhaled treprostinil was well tolerated by PAH patients in routine clinical care, with respiratory-related AEs consistent with the known safety profile (trial registration: clinicaltrials.gov identifier: NCT01266265).

1-Year Results of the REMEDEERegistry: Clinical Outcomes After Deployment of the AbluminalSirolimus-CoatedBioengineered (Combo) Stent inaMulticenter, Prospective All-Comers Registry.

This registry evaluated the safety and clinical outcomes of the Combo stent in an all-comers population in routine clinical practice. We report 1-year results. Limitations of current generation drug-eluting stents (DES) are 3-fold: stent thrombosis, neoatherosclerosis related to impaired healing, and repeat revascularization due to (late-) in-stent restenosis. The Combo stent combines an abluminal biodegradable coating eluting sirolimus and a luminal anti-CD34(+) antibody layer to attract endothelial progenitor cells in order to promote vessel healing, thus preventing neointima formation and restenosis. The REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) post-market registry was an international, multicenter, prospective trial that evaluated clinical outcomes after deployment of the Combo stent, in an all-comers population of patients treated with a Combo stent in the setting of routine clinical care. Clinical endpoints were target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR). Between June 2013 and March 2014, a total of 1,000 patients were included in the registry, 49.9% of whom presented with acute coronary syndrome. Mean age was 65 ± 11 years old (range: 34 to 94 years of age), and 74% ofpatients were male; 58.9% of 1,255 lesions were American Heart Association type B2 or C lesions. The primary endpoints were 5.7% TLF, 1.7% cardiac death, 0.7% target vessel MI, and 4.4% TLR. Definite stent thrombosis occurred in 0.5% of subjects; no thrombosis occurred after 9 days post-stenting. This registry showed excellent 1-year results of novel Combo bioengineered stent technology in an all-comers patient population. (Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE]; NCT01874002).

Incidence and risk factors for neuropsychiatric events among Ghanaian HIV patients on long-term non-nucleoside reverse transcriptase inhibitor-based therapy.

BackgroundNon-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is associated with neuropsychiatric toxicity. Little is known about the risk of short- and long-term neuropsychiatric toxicity in sub-Saharan Africa, where NNRTIs are widely used in first-line combination ART. This observational study assessed the risk of neuropsychiatric toxicity in Ghanaian patients starting first-line ART between 2004 and 2010 at a single centre.MethodsIn this retrospective observational study, frequencies of documented neuropsychiatric toxicity events were assessed and time to events calculated using a Kaplan–Meier analysis. Associations of neuropsychiatric toxicity with specific NNRTIs and other explanatory variables were examined using Cox proportional hazards modelling.ResultsOf 3999 patients initiating NNRTI-based ART, who were followed for a median of 30 (0.25–90) months (11,237 person years), 218 (5.5%) reported symptoms of neuropsychiatric toxicity at a rate of 21.4 events per 1000 person-years (95% CI, 18.8–24.2/1000 py). Events were more common with efavirenz than nevirapine (7.6% versus 2.4%), were usually reported within the first 2 months of ART initiation and persisted up to 84 months in a few patients. The most commonly reported neuropsychiatric adverse drug reactions were insomnia (50%), headaches (8%), dizziness (7%) and abnormal dreams (6%). The factors independently associated with neuropsychiatric toxicity were BMI < 16 kg/m2 (aHR of 1.44 [95% CI, 1.02–2.03]) and use of efavirenz (aHR 3.29 [95% CI, 2.32–4.69]). Substitution of NNRTI on account of toxicity was reported in up to 17% of patients experiencing neuropsychiatric events.ConclusionsNNRTI-related neuropsychiatric toxicity, mainly due to efavirenz, was infrequently documented in this Ghanaian cohort under routine clinical care settings. Regimens with more favourable tolerability will be needed as first-line agents in sub-Saharan Africa in the coming years.

The challenges of implementing ADHD clinical guidelines and research best evidence in routine clinical care settings: Delphi survey and mixed-methods study.

BackgroundThe landmark US Multimodal Treatment of ADHD (MTA) study established the benefits of individualised medication titration and optimisation strategies to improve short- to medium-term outcomes in attention-deficit hyperactivity disorder (ADHD). This individualised medication management approach was subsequently incorporated into the National Institute for Health and Care Excellence (NICE) ADHD Clinical Guidelines (NICE CG78). However, little is known about clinicians’ attitudes towards implementing these medication management strategies for ADHD in routine care.AimsTo examine National Health Service (NHS) healthcare professionals’ consensus on ADHD medication management strategies.MethodUsing the Delphi method, we examined perceptions on the importance and feasibility of implementing 103 ADHD treatment statements from sources including the UK NICE ADHD guidelines and US medication management algorithms.ResultsCertain recommendations for ADHD medication management were judged as important and feasible to implement, including a stepwise titration of stimulant medication. Other recommendations were perceived as important but not feasible to implement in routine practice, such as weekly clinic follow-up with the family during titration and collection of follow-up symptom questionnaires.ConclusionsMany of the key guideline recommendations for ADHD medication management are viewed by clinicians as important and feasible to implement. However, some recommendations present significant implementation challenges within the context of routine NHS clinical care in England.Declaration of interestC.H. and K.S. were members of the Guideline Development Group for the NICE ADHD Clinical Guideline (NICE CG78).Copyright and usage© 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: PHYSIOLOGICAL REACTIVITY TO TRAUMA IMAGERY AS AN OBJECTIVE MEASURE OF TREATMENT RESPONSE.

Physiological reactivity to trauma-related cues is a primary symptom of PTSD and can be assessed objectively using script-driven imagery paradigms. However, subjective self-reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self-reported and clinician-rated symptom measures, patients also completed a script-driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma-specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma-specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms at posttreatment. Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence-based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment.