Weekly IM interferon beta‐1a in multiple sclerosis patients over 50 years of age

Background: Efficacy and safety data have not previously been compiled for intramuscular interferon beta‐1a (IM IFNβ‐1a) in patients with multiple sclerosis (MS) ≥ 50 years of age. We investigated the efficacy and safety of IM IFNβ‐1a in patients segregated by 50 and 40 years of age in separate meta‐analyses. Methods: The MS Clinical Research Group Study, the Controlled High‐Risk Subjects AVONEX^® (IM IFNβ‐1a) MS Prevention Study, the IFNβ‐1a European Dose‐Comparison Study, and a multicenter, open‐label antigenicity and safety study of human serum albumin‐free IM IFNβ‐1a were analyzed. Results: Overall, 906 patients (68 aged ≥ 50 years and 838 aged <50 years, or 323 aged ≥ 40 years and 583 aged <40 years) received IM IFNβ‐1a for ≥ 24 months. At baseline, patients ≥ 50 years had significantly higher Expanded Disability Status Scale scores than patients <50 years (3.4 vs. 2.8; P < 0.001), but fewer relapses in the three preceding years (2.6 vs. 3.4; P < 0.001); patients ≥ 40 years and <40 years exhibited similar differences. After 2 years of treatment, there were no significant differences in annualized relapse rate, sustained disability progression, time to sustained disability progression, or number of MRI‐identified gadolinium‐enhanced lesions between age groups in either analysis. The cumulative probability of relapse was significantly lower in patients ≥ 40 years versus patients <40 years (0.601 vs. 0.702; P < 0.001). Adverse event incidence did not differ significantly between age groups in either analysis. Conclusions: IM IFNβ‐1a is effective and well tolerated in patients with MS ≥ 40 and ≥ 50 years as well as younger patients.     

A prospective, open-label treatment trial to compare the effect of IFN β-1a (Avonex), IFNβ-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis

A prospective, non‐randomized, open‐label treatment trial was performed in patients with relapsing‐remitting multiple sclerosis (RRMS), with follow up for 12 months. Our primary objective was to prospectively compare the effect of IFNβ‐1a (Avonex), IFNβ‐1b (Betaseron), and glatiramer acetate (GA, Copaxone) on the relapse rate in patients with RRMS. Between August 1996 and September 1999, 156 consecutive patients with clinically definite RRMS with a Kurtzke scale (EDSS) score of 4 or less were followed for 12 months, from the time of initiating therapy or electing to remain untreated. Prior 2‐year relapse history and available chart information was carefully reviewed at the time of enrolment. Thirty‐three of 156 elected no treatment (mean age 32.5 years; mean EDSS 2.64) at enrolment; 40 elected IFNβ‐1a (mean age 32.4 years; mean EDSS 2.69), 41 IFNβ‐1b (mean age 32.1 years; mean EDSS 2.56), and 42 chose GA (mean age 31.5 years; mean EDSS 2.57). Annual relapse rate based upon the 2 years prior to enrolment was 1.08 in the untreated group, 1.20 in the AV group, 1.21 in the BE group, and 1.10 in the GA group. There were no statistically significant differences among the four groups at enrolment. After 12 months of treatment, patients in the untreated groups had a relapse rate of 0.97, whereas patients in the IFNβ‐1a, IFNβ‐1b, and GA groups had relapse rate of 0.85, 0.61, and 0.62, respectively. Compared to the untreated group, reduction in the relapse rate was statistically significant only in the GA (P=0.003) and IFNβ‐1b (P=0.002) groups, in contrast to the IFNβ‐1a treated patients, who did not show a significant reduction (P=0.309). Compared to the untreated patients, mean EDSS was significantly reduced only in the GA (P=0.001) and IFNβ‐1b (P=0.01), in contrast to IFNβ‐1a treated patients (P=0.51). In this prospective, controlled, open‐label, non‐randomized 12‐month study, treatment with only GA and IFNβ‐1b significantly reduced the relapse rate compared to untreated patients, supporting early treatment in RRMS. Our results are similar to the observations made after 12 months of therapy in phase III studies of IFNβ‐1a, IFNβ‐1b, and GA. Despite some limitations of the study design, the results provide helpful clinical information regarding the relative efficacy of each therapy in mildly affected treatment‐naïve RRMS patients.     

Adherence to disease-modifying therapies and attitudes regarding disease in patients with multiple sclerosis

Although currently there is no cure for MS the course of the disease can be influenced by disease modifying therapy (DMT). For therapy to be sufficiently efficient, it is crucial that patients take their medication regularly as prescribed. Adherence describes the extent to which a patient acts in accordance with the prescribed timing, dosing, and frequency of medication administration. To date, there are no known data about adherence rates among patients with MS in Slovenia. We wanted to assess adherence in patients with MS, who are treated with first line DMTs and discover reasons for non-adherence. A number of 451 patients were invited to participate. They received two questionnaires via post mail. The adherence rate and putative reasons for non-adherence were assessed by the use of standardized self-report Multiple Sclerosis Treatment Experience Questionnaire (MSTEQ). Patients’ attitudes regarding disease, therapy and relationship with their physician were assessed by another questionnaire. The analysis of results included 299 patients. Among the patients 18.5% missed at least one medication dose in the past 28 days. Patients taking Avonex were significantly more adherent then patients on other DMTs (p = 0.005). Our study showed a higher then expected adherence among Slovenian patients with MS (81.5%). Our research did not confirm the influence of side effects or patients’ attitudes regarding illness and therapy on adherence. However we found unexpectedly high percentage (71.8%) of patients belief that psychological factors are involved in MS aetiology.     

Frequency and severity of headache is worsened by Interferon-β therapy in patients with multiple sclerosis

Patti F, Nicoletti A, Pappalardo A, Castiglione A, Lo Fermo S, Messina S, D’Amico E, Cimino V, Zappia M. Frequency and severity of headache is worsened by Interferon‐β therapy in patients with multiple sclerosis.
Acta Neurol Scand: 2012: 125: 91–95.
© 2011 John Wiley & Sons A/S. Background – The relationship between multiple sclerosis (MS) and headache (HA) is not well known. It was reported that interferon‐beta (IFNβ) could induce or worsen HA. Objective – To evaluate the impact of IFNβ treatment on HA and the relationship between HA and the various commercial preparations of IFNβ in mildly disabled patients with MS. Methods – A specific questionnaire was administered to 357 relapsing‐remitting MS patients. Characteristics of HAs were considered, including the temporal relationships with IFNβ administration. Results – One hundred and seventeen patients were treated with weekly intramuscular injections of interferon IFNβ‐1a (Avonex^®), 84 with subcutaneous injections of IFNβ‐1b (Betaferon^®) every other day, 48 and 108 with three times weekly subcutaneous injections of IFNβ‐1a (Rebif^®) 22 mcg or IFNβ‐1a (Rebif^®) 44 mcg, respectively. Three hundred and fourteen patients were affected by HA, and among them, 219 patients suffered of pre‐existing HA. In this latter group, 121 subjects (55%) noted a worsening of their HA after starting IFNβ therapy; this was more frequently reported by patients treated with Avonex^® and Rebif^® 44. Ninety‐five patients experienced new HA. Conclusion – IFNβ treatment could worsen HA in patients with pre‐existing HA or cause the appearance of new HA. Among different IFNβ preparations, Rebif^® 44 and Avonex^® seemed to be more cephalalgic than the other drugs.     

Factors influencing medication adherence after epilepsy surgery

Aim. In drug‐responsive epilepsy patients, treatment non‐compliance is a major factor in seizure recurrence, but adherence to prescribed regimens following epilepsy surgery has not been examined. We measured adherence to prescribed antiepileptic drugs (AEDs) after epilepsy surgery and investigated factors influencing treatment non‐compliance. Methods. Postsurgical epilepsy patients (n=214) were monitored for 18.1±8.1 months. Adherence was measured using the Medication Possession Ratio (MPR) self‐report questionnaire, with MPR<0.8 defined as non‐adherence. Results. According to the MPR, 58 patients (27.1%) were non‐adherent after surgery. There were no differences in demographic and clinical variables, such as age (p=0.057, t =?1.925), duration of illness (p=0.597, t=0.530), gender ratio (p=0.714, χ²=0.134), and place of residence (urban vs. rural; p=0.874, χ²=0.025), between adherent and non‐adherent patients. Moreover, adherence was not related to surgical outcome as evaluated by the Engel classification (p=0.635, χ²=1.628) or to the types of AEDs after surgery (p=0.165, χ²=6.530). The most common reasons for non‐adherence were seizure‐free status for an extended period (26.5%), forgetfulness (19.1%), and an inability to buy the drugs locally (18.6%). Conclusion. Adherence to AEDs is improved after epilepsy surgery compared to presurgical estimates, but is still a common and serious problem. Targeted postsurgical management programs and communication strategies are necessary to improve adherence to AEDs after epilepsy surgery.     

Inhibitory effects of heterotopic noxious counter‐stimulation on perception and brain activity related to Aβ‐fibre activation

Heterotopic noxious counter‐stimulation (HNCS) inhibits pain and pain processes through cerebral and cerebrospinal mechanisms. However, it is unclear whether HNCS inhibits non‐nociceptive processes, which needs to be clarified for a better understanding of HNCS analgesia. The aim of this study was to examine the effects of HNCS on perception and scalp somatosensory evoked potentials (SEPs). Seventeen healthy volunteers participated in two counter‐balanced sessions, including non‐nociceptive (selective Aβ‐fibre activation) or nociceptive electrical stimulation, combined with HNCS. HNCS was produced by a 20‐min cold pressor test (left hand) adjusted individually to produce moderate pain (mean ± SEM: 42.5 ± 5.3 on a 0–100 scale, where 0 is no pain and 100 the worst pain imaginable). Non‐nociceptive electrical stimulation was adjusted individually at 80% of pain threshold and produced a tactile sensation in every subject. Nociceptive electrical stimulation was adjusted individually at 120% of RIII‐reflex threshold and produced moderate pain (45.3 ± 4.5). Shock sensation was significantly decreased by HNCS compared with baseline for non‐nociceptive (P < 0.001) and nociceptive (P < 0.001) stimulation. SEP peak‐to‐peak amplitude at Cz was significantly decreased by HNCS for non‐nociceptive (P < 0.01) and nociceptive (P < 0.05) stimulation. These results indicate that perception and brain activity related to Aβ‐fibre activation are inhibited by HNCS. The mechanisms of this effect remain to be investigated to clarify whether it involves inhibition of spinal wide‐dynamic‐range neurons by diffuse noxious inhibitory controls, supraspinal processes or both.     

Neurones in the Preoptic Area of the Male Goldfish are Activated by a Sex Pheromone 17α,20β‐Dihydroxy‐4‐Pregnen‐3‐One

Pheromones are interesting molecules given their ability to evoke changes in the endocrine state and behaviours of animals. In goldfish, a sex pheromone, 17α,20β‐dihydroxy‐4‐pregnen‐3‐one (17,20β‐P), which is released by preovulatory females, is known to trigger the elevation of luteinising hormone (LH) levels, as well as reproductive behaviour in males. Interestingly, when 11‐ketotestosterone (11‐KT) is implanted into adult female fish, LH levels increase in response to the pheromone at any time of the day, which is normally a male‐specific response. However, the neural mechanisms underlying the male‐specific information processing of 17,20β‐P and its androgen dependence are yet unknown. In the present study, we focused on the preoptic area (POA), which plays important roles in the regulation of reproduction and reproductive behaviours. We mapped activity in the POA evoked by 17,20β‐P exposure using the immediate‐early gene c‐fos. We found that a population of ventral POA neurones close to kisspeptin2 (kiss2) neurones that appear to have important roles in reproduction was activated by 17,20β‐P exposure, suggesting that these activated neurones are important for the 17,20β‐P response. Next, we investigated the distribution of androgen receptor (ar) in the POA and its relationship with 17,20β‐P‐responsive and kiss2 neurones. We found that ar is widely expressed in the ventral POA, whereas it is only expressed in approximately 10% of 17,20β‐P‐activated neurones. On the other hand, it is expressed in almost 90% of the kiss2 neurones. Taken together, it is possible that ar expressing neurones in the ventral POA, most of which were not labelled by c‐fos in the present study, may at least partly account for androgen effects on responses to primer pheromones; the ar‐positive kiss2 neurones in the ventral POA may be a candidate. These results offer a novel insight into the mechanisms underlying male‐specific information processing of 17,20β‐P in goldfish.     

Identification of new sensitive biomarkers for the in vivo response to interferon‐β treatment in multiple sclerosis using DNA‐array evaluation

Objective: Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)‐β. NAbs impair the effect of treatment. The biological effect of IFN‐β can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other markers could be more sensitive for evaluating the response to IFN‐β. We used DNA array analysis to identify genes that are strongly induced in blood cells by IFN‐β, and measured their expression in MS patients with different NAb levels. Methods: Gene expression was studied on DNA arrays in untreated patients, in NAb negative patients, and in MS patients with varying NAb levels 9–12 h and 36–48 h after IFN‐β administration. The expression of selected genes was measured by real‐time PCR. NAb levels were assessed by a cytopathic effect assay. Results: Several hundred genes were induced 9–12 h after an injection of IFN‐β. The molecules CXCL10, CCL2 and IFI27 were among the most strongly induced. Gene induction was generally much less pronounced after 36–48 h, but IFI27 remained strongly induced. The strong induction of these molecules and MxA was confirmed by real‐time PCR. Induction of MxA, CCL2, CXCL10 and IFI27 was reduced in patients with low NAb levels and lost in patients with intermediate/high NAb levels. Conclusion: We identify IFI27, CCL2 and CXCL10 as sensitive biomarkers for the response to IFN‐β. The expression of these markers adequately reflects bioactivity of IFN‐ß as documented by the decreased induction in low NAb‐positive patients and the lost induction in patients with moderate/high NAb levels.     

Rates and clinical correlates of treatment non-adherence in schizoaffective bipolar patients

Murru A, Pacchiarotti I, Nivoli AMA, Bonnin CM, Patrizi B, Amann B, Vieta E, Colom F. Rates and clinical correlates of treatment non‐adherence in schizoaffective bipolar patients. Objective: To analyze demographical, clinical, and therapeutic variables that may be associated with pharmacological non‐adherence in a sample of schizoaffective patients, bipolar type. Method: Adherence to treatment and its clinical correlates were assessed at the end of a 10‐year follow‐up in 76 patients meeting DSM‐IV‐TR diagnosis of schizoaffective disorder, bipolar type. Adherent and poorly adherent patients were compared regarding clinical and therapeutic variables. Results: The rate of poorly adherent patients was 32/76 (41.2%) of the sample. Adherent patients were more likely to have presented an affective episode at illness onset and to have fewer purely – non‐affective – psychotic episodes. Demographic or other clinical variables were not found to be associated to treatment adherence. Family history for psychiatric disorders or suicide did not correlate either, and neither did any specific pharmacological agent. Conclusion: Rates of non‐adherence in schizoaffective disorder are high. Adherence seems to be associated to a more affective course of illness (affective first episode and fewer purely psychotic episodes). Patients with more prominent schizophrenia‐like characteristics could be at higher risk for poor adherence and need to be closely followed and monitored. Even when properly treated, schizoaffective disorder is a disabling and severe disorder with high risk for recurrences.     

Insulin‐like growth factor (IGF)‐I and IGF‐binding protein‐3 serum levels in relapsing–remitting and secondary progressive multiple sclerosis patients

Background: Insulin‐like growth factor (IGF)‐I has a role in remyelination, and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) might reduce its bioavailability. A role of IGFBP‐3 in multiple sclerosis (MS) progression was hypothesized in patients with primary progressive (PP) MS. Objective: To evaluate serum levels of IGF‐I and IGFBP‐3 in patients with relapsing–remitting (RR) and secondary progressive (SP) MS and their correlations with disease activity and progression. Methods: Sixty‐three (41 RR and 22 SP) ‘naive’ MS patients and 60 age‐matched healthy controls were enrolled. Patients were assessed through clinical [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), number of relapses] and laboratory investigations. IGF‐I and IGFBP‐3 were measured by ELISA. Results: Levels of IGF‐I and IGFBP‐3 were similar in the two MS groups. IGFBP‐3 levels were higher in patients with MS than in controls (P < 0.001), with a reduction in IGF‐I/BP3 ratio (P < 0.001). Patients showing IGFBP‐3 levels higher than 2SD of the normal population had a higher EDSS (mean EDSS 3.7 vs. 2.8, P = 0.021). MSSS was not related to IGF‐I or IGFBP‐3 serum levels. Conclusions: Our patients showed high IGFBP‐3 serum levels respect to controls and higher serum levels were associated with a higher EDSS, despite of comparable disease duration. Therefore, MS and higher disability seem to be associated with a reduction in bioavailability of IGF‐I. MSSS score was not related to IGFBP‐3 levels, suggesting that IGFBP‐3 might not have the pathogenetic role previously suggested for PP MS, in the mechanism of progression in the SP form of disease.     

Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study

Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study. Objective: To identify predictors of non‐remission in first‐episode, non‐affective psychosis. Method: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results: One hundred and twenty‐nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non‐remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non‐remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two‐year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non‐remission at 3 months, but only DUP predicted at 2 years. Conclusion: Long DUP predicted both 3 month and 2‐year non‐remission rates in first‐episode psychosis.     

Tract‐based spatial statistics analysis of diffusion‐tensor imaging data in pediatric‐ and adult‐onset multiple sclerosis

Background: White matter (WM) microstructure may vary significantly in pediatric‐onset (PO) and adult‐onset (AO) patients with multiple sclerosis (MS), a difference that could be explained by the effects of an inherent plasticity in the affected pediatric brains early in the disease, and a phenomenon that does not occur later in life. This hypothesis would support the observation that disease progression is much slower in POMS compared to AOMS patients. Objectives: To examine WM microstructure in the brain of adults with POMS and AOMS, using tract based spatial statistics (TBSS) analysis of diffusion‐tensor imaging (DTI). Methods: Adults with relapsing‐remitting (RR) POMS, who were diagnosed before age of 18 years (n = 16), were compared with age‐matched (AOA, n = 23) and disease duration‐matched (AOD, n = 22) RR patients who developed MS after the age of 18 years. Scans were analyzed using the FSL software package (Oxford, UK) and statistics were performed using TBSS to evaluate WM microstructure between groups based on the mean fractional anisotropy (FA) values obtained from the DTI. Results: Widespread cortical and deep WM area differences characterized by increased FA values were seen in the AOAMS compared with POMS group (P < 0.05, TFCE corrected). Significantly increased FA values of posterior WM areas were detected in the AODMS compared with POMS group (P < 0.05, TFCE corrected). Conclusion: Increased FA values in WM areas of the AOMS compared with the POMS patients suggest that diffuse WM microstructure changes are more attributable to age of onset than a simple function of disease duration and age. Hum Brain Mapp 35:53–60, 2014. © 2012 Wiley Periodicals, Inc.     

Different responses to interferon beta‐1b treatment in patients with neuromyelitis optica and multiple sclerosis

Background: Although the benefit of treatment for relapsing–remitting multiple sclerosis (MS) is firmly established, whether interferon beta‐1b (IFNB‐1b) therapy is efficacious for neuromyelitis optica (NMO) has been debated. Methods: We reviewed the responses to IFNB‐1b treatment in 18 patients with relapsing NMO and compared the results with those from 38 patients with relapsing–remitting MS. We compared clinical characteristics, the annualized relapse rate (ARR) and the probability of being relapse free before and after IFNB‐1b treatment in patients with NMO and MS. Results: The proportion of patients with more than 50% increase in the ARR after IFNB‐1b treatment was much higher in NMO than in MS (P = 0.046). ARR was significantly lower in patients with MS after IFNB‐1b administration than before (P = 0.015), but not in NMO. Kaplan–Meier and log‐rank statistical analyses revealed that relapse‐free rates were lower in NMO than MS after IFNB‐1b treatment (P = 0.032). The analyses also showed lower relapse‐free rates during the pre‐IFNB‐1b treatment period than the post‐IFNB‐1b treatment period in MS (P < 0.001), but not in NMO. Conclusion: IFNB‐1b treatment does not appear to be effective for preventing relapse in NMO likely because of differences between the immune‐pathogenesis of NMO and MS.     

Non‐adherence to interferon‐beta therapy in Swedish patients with multiple sclerosis

Cunningham A, Gottberg K, von Koch L, Hillert J. Non‐adherence to interferon‐beta therapy in Swedish patients with multiple sclerosis.
Acta Neurol Scand: 2010: 121: 154–160.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To explore the occurrence and reasons for stopping, switching or continuing first prescribed interferon‐beta therapy in patients with multiple sclerosis in Sweden, with respect to demographic, clinical and/or therapy‐related factors. Materials and methods – A retrospective study reviewing the medical charts of 259 patients with multiple sclerosis, comparing patients continuing therapy for at least 3 years with those switching or stopping therapy. Results – Sixty 9% stopped (15%), or switched (54%), interferon‐beta therapy within 3 years. Stoppers had longer disease duration before starting therapy (P = 0.002), less frequently relapsing‐remitting multiple sclerosis (P = 0.046), and more often Expanded Disability Status Scale scores 6–9.5 (P = 0.045) compared to Switchers. The most common reasons for switching/stopping therapy were perceived lack of effect and side‐effects. Conclusions – Adherence to initial immune‐modulating therapy is low; identification of patients at higher risk of stopping therapy and provision of adequate support are essential.     

Automated impedance‐manometry analysis detects esophageal motor dysfunction in patients who have non‐obstructive dysphagia with normal manometry

Background Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non‐obstructive dysphagia (NOD) and normal manometry (NOD/NM). Methods Combined impedance‐manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB‐based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp‐PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables. Key Results Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non‐specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance‐manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance‐pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD. Conclusions & Inferences Compared with conventional pressure‐impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry.     

A 2‐year follow‐up of involuntary admission’s influence upon adherence and outcome in first‐episode psychosis

Opjordsmoen S, Friis S, Melle I, Haahr U, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Simonsen E, Vaglum P, McGlashan TH. A 2‐year follow‐up of involuntary admission’s influence upon adherence and outcome in first‐episode psychosis. Objective: To see, if voluntary admission for treatment in first‐episode psychosis results in better adherence to treatment and more favourable outcome than involuntary admission. Method: We compared consecutively first‐admitted, hospitalised patients from a voluntary (n = 91) with an involuntary (n = 126) group as to psychopathology and functioning using Positive and Negative Syndrome Scale and Global Assessment of Functioning Scales at baseline, after 3 months and at 2 year follow‐up. Moreover, duration of supportive psychotherapy, medication and number of hospitalisations during the 2 years were measured. Results: More women than men were admitted involuntarily. Voluntary patients had less psychopathology and better functioning than involuntary patients at baseline. No significant difference as to duration of psychotherapy and medication between groups was found. No significant difference was found as to psychopathology and functioning between voluntarily and involuntarily admitted patients at follow‐up. Conclusion: Legal admission status per se did not seem to influence treatment adherence and outcome.