Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1ß and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth.

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.

Rehabilitation in childhood-onset hyperkinetic movement disorders including dystonia: Treatment change in outcomes across the ICF and feasibility of outcomes for full trial evaluation.

BACKGROUND: Childhood-onset hyperkinetic movement disorders (HMD), including dystonia are notoriously difficult to treat and there are limited studies showing successful medical, surgical or non-pharmacological interventions. METHODS: This prospective study used grouped data (n = 22) from two studies of the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach for patient-selected goals. Eligibility included aged 6-21 years, deep brain stimulation in place, with manual ability classification system level I-IV. Outcome was assessed on a range of patient-reported and clinician-rated measures across the International Classification of Function at end-treatment (10 weekly sessions) (series 1 and 2) and 3-month follow-up (series 1). Feasibility of outcomes to be used in a full trial were explored. FINDINGS: Nineteen participants completed the intervention and were included in the analysis. Of the primary outcome measures, the self-reported Canadian Occupational Performance Measure showed improvement in goal performance (mean change 4.08, 95% CI [3.37,4.79] post-; 4.18 [5.10,5.26] follow-up), and satisfaction (4.03 [3.04,5.03) post-; 4.44 [3.07,5.82] follow-up]. The Assessment of Motor and Process Skills showed improved motor score (0.52 [0.01,1.03] at follow-up only, while the process score did not change. Objective blind-rated pooled data using the Performance Quality Rating Scale-individualized indicated significant change for trained goals (3.79 [3.37,4.21] post-; (4.01,5.10) follow-up] and untrained goals (1.90 [1.24,2.55] post 1.91 [0.23,3.60] follow-up]. Motor impairment assessed by the Burke-Fahn Motor Disability Rating Scale was unchanged (-3.26 [-6.62,0.09] post-; -1.11 [-8.05,5.82] follow-up). Improvement was also observed in self-efficacy (0.97 [0.47,1.47] post-; 1.37 [1.91-0.83] follow-up) and Quality of Life (0.12 [0.03-0.22] follow-up). Goal improvement; self-efficacy and quality of life captured significant change post-intervention. This improvement was shown despite no change on impairment-related measures and were shown to be feasible measures to use in a larger study of CO-OP for this population.

Erratum: Author Correction: Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease.

[This corrects the article DOI: 10.1038/s41531-019-0102-8.].

Lactobacillus-Depleted Vaginal Microbiota in Pregnant Women Living With HIV-1 Infection Are Associated With Increased Local Inflammation and Preterm Birth.

Background: Pregnant women living with HIV-1 infection (PWLWH) have an elevated risk of preterm birth (PTB) of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of PWLWH in a UK population. Methods: Prospective study of PWLWH (n = 53) in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. Cross-sectional characterisation of vaginal microbiota in PWLWH were compared with 22 HIV uninfected pregnant women (HUPW) at a similar second trimester timepoint. Within PWLWH the relationships between bacterial composition, inflammatory response, and gestational age at delivery were explored. Findings: There was a high rate of PTB among PWLWH (12%). In the second trimester the vaginal microbiota was more diverse in PWLWH than in HUPW (Inverse Simpson Index, p = 0.0004 and Species Observed, p = 0.009). PWLWH had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15 vs 54%) than HUPW and higher prevalence of L. iners dominant (VMB III, 36 vs 9% and VMB IIIB, 15 vs 5%) and mixed anaerobes (VMB IV, 21 vs 0%). Across the second and third trimesters in PWLWH, VMB III/IIIB and IV were associated with PTB and with increased local inflammation [cervicovaginal fluid (CVF) cytokine concentrations in upper quartile]. High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably IL-1ß. Interpretation: There is an association between local inflammation, vaginal dysbiosis and PTB in PWLWH. Understanding the potential of antiretroviral therapies to influence this cascade will be important to improve birth outcomes in this population.

Cognitive Strategy Training in Childhood-Onset Movement Disorders: Replication Across Therapists.

Objective: To explore preliminary effectiveness of the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach in improving outcomes in childhood-onset hyperkinetic movement disorders (HMDs) including dyskinetic cerebral palsy following deep brain stimulation (DBS) across UK clinical occupational therapists. Methods: Randomized, multiple-baseline, Single Case Experimental Design N-of-1 trial with replications across participants. Five self-selected goals were identified: three goals were worked on during CO-OP and two goals were left untreated and used to assess skills transfer. Participants were between 6 and 21 years and had received DBS surgery with baseline Manual Ability Classification System (MACS) levels I-IV. Participants were randomized to typical or extended baseline (2 vs. 6 weeks), followed by 10 weekly individual CO-OP sessions. The primary outcome was functional performance measured by the Performance Quality Rating Scale-Individualized (PQRS-I), assessed before, during, and following treatment. Outcome assessors were blinded to baseline allocation, session number, and assessment time. A non-overlapping index, Tau-U, was used to measure effect size. Results: Of the 12 participants recruited, 10 commenced and completed treatment. In total, 63% of trained goals improved with effect sizes 0.66-1.00 ("moderate" to "large" effect), seen for all children in at least one goal. Skills transfer was found in 37% of the untrained goals in six participants. Conclusions: Cognitive strategy use improved participant-selected functional goals in childhood-onset HMD, more than just practice during baseline. Preliminary effectiveness is shown when the intervention is delivered in clinical practice by different therapists in routine clinical settings.

Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease.

Anxiety is a severe problem for at least one-third of people living with Parkinson's disease (PD). Anxiety appears to have a greater adverse impact on quality of life than motor impairment. Despite its high prevalence and impact on daily life, anxiety is often undiagnosed and untreated. To better address anxiety in PD, future research must improve knowledge about the mechanism of anxiety in PD and address the lack of empirical evidence from clinical trials. In response to these challenges, the Parkinson's Foundation sponsored an expert meeting on anxiety on June 13th and 14th 2018. This paper summarizes the findings from that meeting informed by a review of the existing literature and discussions among patients, caregivers, and an international, clinician-scientist, expert panel working group. The goal is to provide recommendations to improve our understanding and treatment of anxiety in PD.

Barriers to reporting non-motor symptoms to health-care providers in people with Parkinson's.

BACKGROUND: Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. METHODS: 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. RESULTS: A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). CONCLUSION: A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being.

Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly.

BACKGROUND: Congenital uterine anomalies are associated with late miscarriage and spontaneous preterm birth. OBJECTIVE: Our aim was 1) to determine the rate of spontaneous preterm birth in each type of congenital uterine anomaly, and 2) to assess the performance of quantitative fetal fibronectin and cervical length measurement by transvaginal ultrasound in asymptomatic women with congenital uterine anomalies for the prediction of spontaneous preterm birth at <34 and <37 weeks of gestation. MATERIALS AND METHODS: This was a retrospective cohort of women with congenital uterine anomalies asymptomatic for spontaneous preterm birth, from 4 tertiary referral centers in the United Kingdom (2001-2016). Congenital uterine anomalies were categorized into fusion (unicornuate, didelphic, and bicornuate uteri) or resorption defects (septate, with or without resection, and arcuate uteri), based on prepregnancy diagnosis. All women underwent serial transvaginal ultrasound cervical length assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent quantitative fetal fibronectin testing from 18 weeks' gestation. We investigated the relationship between congenital uterine anomalies and predictive test performance for spontaneous preterm birth at <34 and <37 weeks' gestation. RESULTS: A total of 319 women were identified as having congenital uterine anomalies in our high-risk population. Of the women, 7% (23/319) delivered spontaneously at <34 weeks' gestation and 18% (56/319) at <37 weeks' gestation. Rates of spontaneous preterm birth by type were as follows: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate, and 31% (4/13) for arcuate. In all, 80% (45/56) of women who had spontaneous preterm birth at <37 weeks did not develop a short cervical length (<25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short cervical length had a low sensitivity (20.3) for predicting spontaneous preterm birth at <34 weeks. Cervical length had an area under the receiver operating curve of 0.56 (95% confidence interval, 0.48-0.64) and 0.59 (95% confidence interval, 0.55-0.64) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for cervical length to predict spontaneous preterm birth at <34 weeks was 0.48 for fusion defects (95% confidence interval, 0.39-0.57) but 0.78 (95% confidence interval, 0.66-0.91) for women with resorption defects. Overall quantitative fetal fibronectin had an area under the curve of 0.63 (95% confidence interval, 0.49-0.77) and 0.58 (95% confidence interval, 0.49- 0.68) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for prediction of spontaneous preterm birth at <37 weeks with quantitative fetal fibronectin for fusion defects was 0.52 (95% confidence interval, 0.41-0.63) but 0.79 (95% confidence interval, 0.63-0.95) for women with resorption defects. Results were similar when women with intervention were excluded. CONCLUSION: The commonly used markers cervical length and quantitative fetal fibronectin have utility in prediction of spontaneous preterm birth in resorption congenital uterine defects but not in fusion defects. This is contrary to findings in other high-risk populations. These findings need to be accounted for when planning antenatal care, and have potential implications for predictive tests used in spontaneous preterm birth surveillance and intervention.

Motor fluctuations and psychological distress in Parkinson's disease.

OBJECTIVES: Off periods in Parkinson's disease are associated with a worsening of nonmotor symptoms and acute psychological distress. The relationship between motor fluctuations and episodic distress in naturalistic settings remains unclear, particularly the role of individual psychological factors. This study aimed to identify those factors through real-life, real-time assessment using ecological momentary assessment (EMA). METHOD: Twenty participants (seven female) completed multiple brief prompted surveys over a 7-day period assessing current motor and medication state, social situation, episodic distress, and cognitive processes (rumination, symptom focus, and worry). Baseline depression and anxiety were measured using validated questionnaires, as were positive and negative beliefs and attitudes (metacognitions) regarding cognitive processes. The feasibility of EMA via smartphones was assessed at the end of the study. RESULTS: Across participants, 496 complete data sets were collected. Generalized linear mixed-model regression analyses showed that episodic distress was predicted by a combination of cognitive processes, F(1, 483) = 41.14, p < .001, momentary motor state, F(3, 483) = 10.40, p < .001, time of day, F(1, 23) = 12.42, p = .002, and trait negative metacognitions, F(1, 6) = 7.21, p = .037). EMA was judged acceptable by the majority of participants. CONCLUSIONS: Time of day, cognitive processes, and negative metacognitions predict episodic distress independent of motor state. This indicates potential targets for nonpharmacological interventions aimed at alleviating episodic distress in patients with motor fluctuations. EMA is a feasible methodology for Parkinson's disease research and potential tool for delivering such interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognitive approach to rehabilitation in children with hyperkinetic movement disorders post-DBS.

OBJECTIVE: This proof-of-concept feasibility trial examined the potential of the Cognitive Orientation to daily Occupational Performance Approach (CO-OP) to augment deep brain stimulation (DBS) outcomes in childhood-onset hyperkinetic movement disorders (HMD) including dystonia and dyskinetic cerebral palsy. METHODS: This is a single case experimental design using multiple baseline as n-of-1 trial comprising 10 intervention sessions, with replications across participants (n = 10). Treatment focused on 3 participant-selected goals. Transfer was assessed on 2 additional untreated goals. Individuals enrolled were 6-21 years of age and had DBS in situ and sufficient manual ability. Primary outcome was functional performance change on the Performance Quality Rating Scale-Individualized (PQRS-i) measured before, during, and posttreatment, and at 3-month follow-up. Assessors of outcome were blinded to time of assessment, number of intervention session, and treatment allocation. To measure effect size, a nonoverlapping index, Tau-U, was used. Feasibility measures were captured. RESULTS: One participant withdrew before baseline assessment. Effect sizes of at least 0.66 were seen at both posttreatment and follow-up with all participants showing improvements in at least one trained goal in PQRS-i. Six participants improved on all 3 goals and 2 improved on 2 trained goals. Two children showed deterioration in one trained goal each. Transfer to untrained goals was observed in 3 participants for a total of 5 goals. CO-OP was feasible and acceptable to all participants. CONCLUSION: A cognitive-based, task-oriented approach to support performance of personally relevant functional skills enabling participation is acceptable in childhood-onset HMD post-DBS. Further, preliminary efficacy to improve outcomes and proof of concept with CO-OP has been established in this population. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with HMD who had undergone DBS, CO-OP improves performance of personally relevant functional skills.

Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes.

Vaginal bacterial community composition influences pregnancy outcome. Preterm prelabor rupture of the fetal membranes (PPROM), which precedes 30% of all spontaneous preterm births, is associated with high vaginal bacterial diversity prior to rupture. The point at which vaginal bacterial diversity is established before PPROM is unknown. In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n = 38) and low (n = 22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n = 36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term. PPROM was associated with instability of bacterial community structure during pregnancy and a shift toward higher diversity predominately occurring during the second trimester. This was characterized by increased relative abundance of potentially pathogenic species including Prevotella, Peptoniphilus, Streptococcus, and Dialister. This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth.

Identifying barriers to help-seeking for non-motor symptoms in people with Parkinson's disease.

Non-motor symptoms of Parkinson's disease have a significant impact on quality of life. Despite this, many non-motor symptoms remain unreported by patients and consequently untreated. This study explored barriers to help-seeking using two theoretical frameworks, the Common Sense Model of illness perception and Theoretical Domains Framework. A total of 20 participants completed semi-structured interviews to explore symptom beliefs and help-seeking behaviour. Uncertainty about the relationship of non-motor symptoms to Parkinson's disease and lack of clarity around treatments were common. Embarrassment and communication difficulties were common for potentially sensitive symptoms such as sexual dysfunction. Symptom perceptions and beliefs about help-seeking acted as barriers to reporting non-motor symptoms.

Protocol for N-of-1 trials proof of concept for rehabilitation of childhood-onset dystonia: Study 1: Protocole des essais de validation à effectif unique pour la réadaptation de la dystonie débutant dans l'enfance : Étude 1.

BACKGROUND: Hyperkinetic movement disorders (HMD) are a heterogeneous group of neurological conditions among which dystonia is the predominant disorder and dyskinetic cerebral palsy the largest secondary dystonia group. Currently, there are no evidence-based, non-medical management options for childhood HMD. The Cognitive Orientation to daily Occupational Performance (CO-OP) Approach is a task-oriented, performance-based intervention that focuses on participation. PURPOSE: This paper reports the protocol for a proof-of-concept study to assess feasibility and preliminary evidence regarding efficacy of CO-OP for HMD following deep brain stimulation (DBS). METHOD: A series of N-of-1 trials with replications will be conducted with children, ages 6 and 21 years with HMD and DBS as indicated by the Manual Ability Classification System. Ten individualized CO-OP sessions, with multiple baselines before, during, and after, will be completed. The primary outcome measures are the Performance Quality Rating Scale and the Assessment of Motor and Process Skills. Outcome data will be plotted over time for each participant and supplemented with graph statistical analysis and effect size estimates. IMPLICATIONS: A written protocol will be developed based on evidence and feedback incorporating any changes to the CO-OP intervention for children and young people with HMD, as per the Medical Research Council's Framework for Complex Interventions.

Protocol for N-of-1 trials with replications across therapists for childhood-onset dystonia rehabilitation: Study 2: Protocole des essais à effectif unique avec répétitions par différents ergothérapeutes pour la réadaptation de la dystonie débutant dans l'enfance : Étude 2.

BACKGROUND: Currently, no evidence-based rehabilitation interventions are available for hyperkinetic movement disorders (HMD), including dyskinetic cerebral palsy (CP). Among these highly heterogeneous disorders, dystonia is the predominant disorder. The Cognitive Orientation to daily Occupational Performance (CO-OP) Approach-a task-oriented, performance-based intervention to enable participation-is currently being evaluated for its potential as an intervention option. PURPOSE: This paper reports the protocol for the second of two studies designed to evaluate the potential of CO-OP to improve functional outcomes for individuals with HMD following deep brain stimulation (DBS). This second study is a systematic replication across multiple treating therapists from multiple centres. METHOD: Systematic replications will be used across centres and treating therapists trained in the CO-OP, using a series of randomized multiple-baseline N-of-1 trials. Participants will be ages 6 to 21 years with HMD and DBS as indicated by the Manual Ability Classification System. Data collection will involve multiple data points collected at baseline, during intervention, and after intervention. The intervention will involve occupation-based goal setting followed by 10 individualized CO-OP sessions. The primary outcome measures are the Performance Quality Rating Scale and the Canadian Occupational Performance Measure. Outcome data will be plotted over time for each participant and supplemented with graph statistical analysis and estimate size effect for N-of-1 trials. IMPLICATIONS: The results of this study will help to inform future training procedures and future clinical trials.

Implicit Behavioral Change in Response to Cognitive Tasks in Alzheimer Disease.

BACKGROUND AND OBJECTIVE: Lack of awareness about impairments is commonly found in Alzheimer disease (AD), but recent evidence suggests that patients may respond to the experience of illness despite limited awareness. In this study, we explored whether implicit emotional responses to experiences of failure in cognitive tasks would result in longer-term change in behavior. METHODS: Twenty-two patients with AD were seen 1 week after a previous session in which they performed computer tasks that had been manipulated to be either too difficult (failure condition) or very easy (success condition) for them. At the second session, both types of tasks were set to have medium difficulty and were administered so that the participants decided how long to persist on each task. Task persistence was determined by relative time spent doing the tasks, considering that participants would be more likely to stop performing tasks in which they had experienced failure during the first session. RESULTS: Task persistence in the second session was not affected by performance in the first session. However, when participants' awareness of performance in the first session was taken into account, differences were found in persistence between tasks in the second session. During the second session, participants stopped performing tasks after a sequence of errors. There were no self-reported changes in motivation or enjoyment in response to task failure. CONCLUSIONS: These findings suggest that implicit learning of task valence may be compromised in AD, but that initial moments of awareness of performance may influence long-term adaptation in unaware patients.

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.

BACKGROUND: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. METHODS: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. RESULTS: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. CONCLUSIONS: Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Parkinson's Impulse-Control Scale for the Severity Rating of Impulse-Control Behaviors in Parkinson's Disease: A Semistructured Clinical Assessment Tool.

BACKGROUND: Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome). METHODS: The Parkinson's Impulse-Control Scale (PICS), the first PD-specific, semistructured interview to cover the full range of PD-related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92). RESULTS: The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%-95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (Κ) values for clinician-clinician rating of severity (Κ = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive-behavioral therapy and medication adjustment (t[22] = 5.47; P < 0.001). CONCLUSIONS: The PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required.

Randomised, waiting list controlled trial of cognitive-behavioural therapy for persistent postconcussional symptoms after predominantly mild-moderate traumatic brain injury.

BACKGROUND: Persistent postconcussional symptoms (PCS) can be a source of distress and disability following traumatic brain injury (TBI). Such symptoms have been viewed as difficult to treat but may be amenable to psychological approaches such as cognitive-behavioural therapy (CBT). OBJECTIVES: To evaluate the effectiveness of a 12-session individualised, formulation-based CBT programme. METHOD: Two-centre randomised waiting list controlled trial with 46 adults with persistent PCS after predominantly mild-to-moderate TBI (52% with post-traumatic amnesia (PTA)≤24 hours), but including some with severe TBIs (20% with PTA>7 days). RESULTS: Improvements associated with CBT were found on the primary outcome measures relating to quality of life (using the Quality of Life Assessment Schedule and the Brain Injury Community Rehabilitation Outcome Scale). Treatment effects after covarying for treatment duration were also found for PCS and several secondary outcomes, including measures of anxiety and fatigue (but not depression or post-traumatic stress disorder (PTSD)). Improvements were more apparent for those completing CBT sessions over a shorter period of time, but were unrelated to medicolegal status, injury severity or length of time since injury. CONCLUSIONS: This study suggests that CBT can improve quality of life for adults with persistent PCS and potentially reduce symptoms for some, in the context of outpatient brain injury rehabilitation services. TRIAL REGISTRATION NUMBER: ISRCTN49540320.