Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-G) in Down's syndrome.

BACKGROUND: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS-AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS-AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. METHODS: A German version of the DSQIID questionnaire (DSQIID-G) was completed by caregivers before attending our specialist outpatient department for DS-AD. All participants were assessed blind to DSQIID-G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). ICD-10 and amyloid/tau/neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. RESULTS: Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS-AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co-morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID-G total scores [median (range): 3 (0-21) vs. 19 (0-48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS-AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX-DS interview score was good (r = 0.74), and split-half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test-retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. CONCLUSIONS: The DSQIID-G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut-off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID-G, a lower cut-off is preferable to increase case detection.

Bayesian approach for evaluation of lactation curve in cross bred cattle based on monthly and bimonthly test day milk yield.

In field progeny testing program milk recording at monthly or bimonthly intervals and prediction of first lactation 305-day milk yield (FL305DMY) from these test day yields have been adapted as an alternative to daily milk recording. Wood's incomplete gamma function is the one of the commonly used nonlinear lactation curve model. In recent years Bayesian approach of fitting nonlinear biological models is gaining attention among researchers. In this study Wood's incomplete gamma function was fitted using Bayesian approach using monthly (MTDY) and bimonthly test day (BTDY) yields. The lactation curve parameters thus obtained were used for prediction of FL305DMY. Efficiency of prediction based on monthly and bimonthly test day milk yield were compared using error of prediction. It was found to be 5.78% and 7.59% as root mean square error (RMSE) based on MTDY and BTDY respectively.The Breeding values of 97 Karan Fries sires were estimated using BLUP-AM based on actual and predicted FL305DMY thus obtained. The RMSE was calculated as the difference between estimated breeding values based on actual and predicted yield. It was found that RMSE calculated based on MTDY showed only a marginal superiority of 0.79% over BTDY and showed high degree of correlation with actual yield. Therefore, recording at bimonthly intervals could be an economical alternative without compromising the efficiency.

Training support workers about the overmedication of people with intellectual disabilities: an Australian pre-post pilot study.

BACKGROUND: There is evidence that psychotropic medications are overprescribed and overused to manage behaviours of concern for people with intellectual disabilities. Disability support workers and support staff lack education and training on the administration and safety of psychotropic medication use. This study aimed to test the applicability and preliminary efficacy of SPECTROM, an education programme developed in the UK, in an Australian context. METHODS: The training comprises two parts: Module 1 encompasses psychotropic medications, their use and side effects. Module 2 focuses on non-pharmacological interventions for supporting people with behaviours of concern. Thirty-three participants attended the training course and completed pre-training and post-training surveys on the Psychotropic Knowledge Questionnaire and Management of Aggression and Violence Attitude Scale-Revised at four time points: pre-training, 2 weeks, 3 months and 5 months post-training. RESULTS: Psychotropic Knowledge Questionnaire scores showed statistically significant post-training improvement at all post-training time points (P < 0.05). Management of Aggression and Violence Attitude Scale-Revised scores were high at pre-training and did not change significantly at any of the post-training survey time points. A 2-week post-training feedback questionnaire reported 80% agreement that the training programme was appropriate, useful and valid. Only 36% of participants completed questionnaires at all time points. CONCLUSIONS: SPECTROM training increased staff knowledge of psychotropic medications, yet loss of participants was high. Further refinement of the applicability of the training for the Australian context and evaluation of the feasibility of implementation, clinical and cost-effectiveness of the programme are required.

A laboratory study to assess the formation of effluent volatile compounds and disinfection by-products during chemomechanical preparation of infected root canals and application of activated carbon for their removal.

AIM: To assess in a laboratory setting using extracted teeth the formation of volatile compounds (VOCs) and disinfection by-products (DBPs) in effluent aliquots, during chemomechanical preparation of artificially infected root canal specimens, and determine the role of silver-impregnated activated carbon (Ag-AC) in their removal. METHODOLOGY: Single-rooted human teeth were decoronated to obtain 15 mm-long root specimens and a nutrient-stressed multispecies biofilm was grown in the root canals. Specimens were randomly assigned into three groups [Group 1; instrumentation with rotary files and irrigation with sterile saline, Groups 2 and 3; instrumentation with rotary files and irrigation with 2.5% NaOCl and 17% EDTA]. A portable medical suction device was used to collect the effluent aliquots during root canal irrigation. In Groups 1 and 2, the reaction products of the collected effluents were analysed by selected ion flow tube mass spectrometry (SIFT-MS). The effluents from Group 3 were treated with Ag-AC prior to SIFT-MS analysis, to assess the removal capacity of Ag-AC against the reaction products. The synthesis of Ag-AC was characterized with scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS). Two-way analysis of variance (anova) with post hoc Tukey tests was used for data analysis and determination of a significant difference (P < 0.05). RESULTS: In Group 1, effluent VOCs and DBPs were detectable at very low levels. In Group 2, the collected effluent aliquots released high concentrations of methanol, propanol, ammonia, chloroform and formaldehyde, which were significantly greater compared to Group 1 (P < 0.001). SEM/EDS analysis confirmed impregnation of Ag within the AC matrix. The treatment of effluent aliquots with Ag-AC (Group 3) resulted in a significant reduction in concentrations of acetone, acetic acid, propanol, acetaldehyde, acetonitrile and chloroform, compared to Group 2 (P < 0.001). The concentration levels of ethanol, methanol, ammonia and formaldehyde remained unaffected (P > 0.05). CONCLUSIONS: In this laboratory setting using extracted human teeth, the chemomechanical preparation of artificially infected root canals resulted in the formation of toxic VOCs and DBPs as effluent suspensions. Their release during aspiration with dental suction indicates that potential environmental hazards should be investigated. The use of silver-impregnated activated carbon had potential for the point-of-use treatment of post-irrigation effluent aliquots.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Adverse childhood experiences: association with physical and mental health conditions among older adults in Bhutan.

OBJECTIVES: Adverse childhood experiences (ACEs) are events stressful, traumatic, and related to the development of a wide range of health conditions throughout the person's lifespan. This study explored the relationship between ACEs and health conditions among older adults in Bhutan. STUDY DESIGN: Cross-sectional survey. METHODS: Older adults aged 60-101 years (n = 337) completed a face-to-face interview in a convenient community setting in the four major towns of Bhutan. Measurements included the modified World Health Organization Adverse Childhood Experiences International Questionnaire and the checklist of chronic health conditions. RESULTS: Commonest ACEs reported by the sample were related to the contribution of physical labour in childhood (n = 284 [84.3%]) and witnessing of community violence (n = 185 [54.9%]). Assuming an adult role while still a child highly co-occur with other forms of ACEs. Compared to 0-2 ACEs, participants with ≥7 ACEs had the higher odds of reporting lung disease (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.03-4.49), visual impairment (OR = 2.38, 95%CI: 1.16-4.85), insomnia (OR = 2.35, 95%CI: 1.11-4.98), and memory decline (OR = 2.30, 95%CI: 1.10-4.78) by twofold and high blood pressure by threefold (OR = 3.21, 95%CI: 1.39-7.38). Overall, the odds of self-rated poor health conditions among those ≥7 ACEs compared to 0-2 ACEs was high by almost twofold (OR = 1.97; 95%CI: 1.04-3.73). CONCLUSIONS: The influence of ACEs on health conditions persisted into late adulthood, and older people in Bhutan have had a complex variety of chronic health conditions implicating greater demand on the free healthcare system in Bhutan. ACEs prevention is critical to promote better health for a country like Bhutan, where the healthcare services are provided free of cost to its citizens.

High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists.

This study evaluated the chronic effects of nitrate (NO3-) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO2max: 60.8 ± 7.4 ml.kg-1.min-1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of "BEET It sport®" NO3- shot containing 12.8 mmol or 800 mg of NO3-, a placebo drink or nothing (control). Performance, oxygen consumption (VO2), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO3- ingestion had no effect on TT performance (NO3-: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO2 (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO3- over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.

Filament Nucleation Tunes Mechanical Memory in Active Polymer Networks.

Incorporating growth into contemporary material functionality presents a grand challenge in materials design. The F-actin cytoskeleton is an active polymer network which serves as the mechanical scaffolding for eukaryotic cells, growing and remodeling in order to determine changes in cell shape. Nucleated from the membrane, filaments polymerize and grow into a dense network whose dynamics of assembly and disassembly, or 'turnover', coordinates both fluidity and rigidity. Here, we vary the extent of F-actin nucleation from a membrane surface in a biomimetic model of the cytoskeleton constructed from purified protein. We find that nucleation of F-actin mediates the accumulation and dissipation of polymerization-induced F-actin bending energy. At high and low nucleation, bending energies are low and easily relaxed yielding an isotropic material. However, at an intermediate critical nucleation, stresses are not relaxed by turnover and the internal energy accumulates 100-fold. In this case, high filament curvatures template further assembly of F-actin, driving the formation and stabilization of vortex-like topological defects. Thus, nucleation coordinates mechanical and chemical timescales to encode shape memory into active materials.

Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study.

OBJECTIVES: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN: Population-based pregnancy cohort. SETTING: Medical records (CPRD-GOLD) from England. POPULATION: 417 028 pregnancies during 1998-2014. METHODS: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES: NVP/HG diagnoses, treatments, and hospital admissions. RESULTS: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first-line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment). CONCLUSION: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. TWEETABLE ABSTRACT: The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions.

Ray sum image: its efficacy in renal tract calculus detection.

AIM: To determine the efficacy of a ray sum image derived from computed tomography of the kidneys, ureters and bladder (CT KUB) in detecting renal tract calculi and whether this can replace the baseline abdominal radiograph (AXR). MATERIALS AND METHODS: This is a retrospective study performed at a tertiary referral centre examining adult patients referred for urolithiasis who had undergone AXR within 24 hours of the diagnostic CT KUB. AXR and ray sum image for calculus visibility were reviewed blindly by two readers. Anteroposterior thickness of the patient, presence of excess gas/faecal material, calculus size, location, and mean attenuation were analysed to determine effect on the AXR and ray sum sensitivity. RESULTS: One hundred and fifty-two calculi were examined with ray sum image sensitivity of 44% (95% confidence interval [CI]: 36-52) and AXR 30% (95% CI: 22-38). Calculus size and mean attenuation significantly affected sensitivities of both ray sum and AXR. There was substantial agreement between the two techniques with κ(Kappa)=0.70 (95% CI: 0.58-0.81, p<0.001). CONCLUSION: Ray sum image as a post-processed image derived from CT KUB dataset may be a viable alternative to the baseline AXR in patients with CT proven urolithiasis. This would reduce patient radiation dose and streamline workflow in busy radiology and emergency departments.

Patient powered prophylaxis: A 12-month study of individualized prophylaxis in adults with severe haemophilia A.

INTRODUCTION: Adults with severe haemophilia A (SHA) may experience breakthrough bleeds despite standard weight-based FVIII prophylaxis three times weekly. Individualized prophylaxis has evolved to optimize patient outcomes. AIMS: This study aimed to evaluate the impact of a standardized approach to individualized prophylaxis on annualized bleeding rates (ABR), factor utilization, physical activity and quality of life in adults with SHA. METHODS: In this prospective cohort study, patients with baseline FVIII:C <2% and ABR >3 on weight-based prophylaxis received a standardized approach to individualized prophylaxis. Changes in ABR, annualized FVIII consumption and adherence from the 12-month prestudy and 12-month intervention period were compared. Changes in Haemo-QoL-A total score, Physical Functioning (PF) subscale and physical activity level measured by accelerometry were also examined. RESULTS: Eighteen patients participated (median age 26 years). Individualized prophylaxis decreased total bleeds in the population by 69% and traumatic bleeds by 73%. The median ABR decreased from 7.5 to 2 (P<.001). Annualized factor consumption increased by 7.3%, as a result of 66% reduction in factor utilization for treatment of bleeds and 25% increase in factor utilization for prophylaxis. Adherence scores for frequency and dosing did not change. There was a significant increase in the Haemo-QoL-A total score (P=.02) and PF score (P=.01) from baseline to 4 months but no change in physical activity. CONCLUSION: Patients with SHA who switched from standard to individualized prophylaxis show reduced ABR and increased FVIII consumption, and also improved their health-related quality of life. The mechanism is independent of adherence to prescribed prophylactic regimen.

Anxiety associated with diagnostic uncertainty in early pregnancy.

OBJECTIVES: To determine anxiety levels of women presenting to an early pregnancy assessment unit (EPAU) with abdominal pain and/or vaginal bleeding and to assess how these levels change over time and according to ultrasonographic diagnosis. METHODS: We undertook a prospective cohort study in an EPAU in a large UK teaching hospital. Women with abdominal pain and/or vaginal bleeding in early pregnancy (< 12 weeks' gestation) presenting for the first time were eligible for inclusion in the study. State anxiety levels were assessed using the standardized short form of Spielberger's state-trait anxiety inventory (STAI) on three occasions (before, immediately after and 48-72 hours after an ultrasound scan). Scores were correlated with ultrasonographic diagnosis. The diagnosis was either certain or uncertain. Certain diagnoses were either positive, i.e. a viable intrauterine pregnancy (IUP), or negative, i.e. a non-viable IUP or ectopic pregnancy. Uncertain diagnoses included pregnancy of unknown location and pregnancy of uncertain viability. Statistical analysis involved mixed ANOVAs and the post-hoc Tukey-Kramer test. RESULTS: A total of 160 women were included in the study. Anxiety levels decreased over time for women with a certain diagnosis (n = 128), even when negative (n = 64), and increased over time for women with an uncertain diagnosis (n = 32). Before the ultrasound examination, anxiety levels were high (STAI value, 21.96 ± 1.11) and there was no significant difference between the five groups. Immediately after the ultrasound examination, anxiety levels were lower in the viable IUP group (n = 64; 7.75 ± 1.13) than in any other group. The difference between the five groups was significant (P < 0.005). After 48-72 hours, women with a certain diagnosis had significantly lower anxiety levels than had those with an uncertain diagnosis (10.77 ± 4.30 vs 22.94 ± 1.65; P < 0.005). CONCLUSIONS: The experience of abdominal pain and/or vaginal bleeding in early pregnancy is highly anxiogenic. Following an ultrasound examination, the certainty of the diagnosis affects anxiety levels more than does the positive or negative connotations associated with the diagnosis per se. Healthcare providers should be aware of this when communicating uncertain diagnoses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cytohistological correlation in pituitary tumor and immunological assessment with the help of Ki-67.

BACKGROUND: Tumors of the pituitary gland and sellar region represent approximately 10-15% of all brain tumors. Pituitary adenoma (PA), the most common pathology of the pituitary gland, can be effectively subclassified only with the help of immunohistochemistry (IHC). This is important and needed for individual patient management. AIMS AND OBJECTIVES: The objective of the study was to analyze the importance of intraoperative imprint smear cytology and correlating with final histopathological diagnosis. Furthermore, to classify the different types of PA with the help of IHC, prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH) and to predict the benign, atypical, or malignant nature of the tumor with the help of prognostic marker Ki-67. MATERIALS AND METHODS: A prospective study was done in 34 cases. The patients whose pituitary gland samples are referred from the endocrine and the neurosurgery department to the pathology department for histopathological examinations were selected. We have studied the clinical features, radiology and touch imprint cytology, histopathology, and IHC with the help of PRL, ACTH, GH, and Ki-67 of PA over 2 years. RESULTS: In our study, we had 32 cases of PA of 34 cases over a span of 2 years. We have seen that there is a correlation between cytological and histological diagnosis of the subtypes of PA in 62% cases, and the Kappa statistics show a moderate extent of agreement (Kappa - 0.320, 95% confidence interval = 0.031-0.609). Ki-67 when compared to the radiological grading showed a high degree of comparability (Chi-square test: P < 0.001). All cases with invasion had a higher Ki-67. On using the Fisher's exact test, we found that the Ki-67 expression with GH-producing adenomas and ACTH-producing adenomas was comparable (P = 1.000) while in PRL-producing adenomas too this was not significant (P = 0.269). CONCLUSION: PA can be effectively classified with the help of IHC. Intraoperative cytology is important in diagnosing PA, but histopathology remains the gold standard in diagnosing and differentiating PA from other pathologies of the pituitary gland. The radiological grading together with immunological classification and the prognostic markers of Ki-67 is important in deciding the benign or atypical nature of the adenomas thus helping in better patient management.

Older Stroke Patients with High Stroke Scores Have Delayed Door-To-Needle Times.

INTRODUCTION: The timely administration of intravenous (IV) tissue plasminogen activator (t-PA) to acute ischemic stroke patients from the period of symptom presentation to treatment, door-to-needle (DTN) time, is an important focus for quality improvement and best clinical practice. METHODS: A retrospective review of our Get With The Guidelines database was performed for a 5-hospital telestroke network for the period between January 2010 and January 2015. All acute ischemic stroke patients who were triaged in the emergency departments connected to the telestroke network and received IV t-PA were included. Optimal DTN time was defined as less than 60 minutes. Logistic regression was performed with clinical variables associated with DTN time. Age and National Institutes of Health Stroke Scale (NIHSS) score were categorized based on clinically significant cutoffs. RESULTS: Six-hundred and fifty-two patients (51% women, 46% White, 45% Hispanic, and 8% Black) were included in this study. The mean age was 70 years (range 29-98). Of the variables analyzed, only arrival mode, initial NIHSS score, and the interaction between age and initial NIHSS score were significant. DTN time more than or equal to 60 minutes was most common in patients aged more than 80 years with NIHSS score higher than 10. CONCLUSIONS: The cause of DTN time delay for older patients with higher NIHSS score is unclear but was not related to presenting blood pressure or arrival mode. Further study of this subgroup is important to reduce overall DTN times.

Characteristics and the trajectory of psychotropic medication use in general and antipsychotics in particular among adults with an intellectual disability who exhibit aggressive behaviour.

BACKGROUND: A high proportion of adults with an intellectual disability (ID) are known to receive psychotropic medications for the management of aggressive behaviour in the absence of any psychiatric diagnosis. Despite this widespread use of psychotropic medication in general and antipsychotic medication in particular, no study has reported the trajectory of psychotropic medication use using a prospective design. METHOD: We have prospectively studied a community, clinic-based sample of 100 adults with ID and aggressive behaviour over a 6-month period for use of psychotropic medication in general and antipsychotics in particular, and compared them with demographic, psychiatric and behavioural variables. RESULTS: Psychotropic medications were used for 89% of patients at baseline (T1) and 90% at 6 months' (T2) follow-up. Risperidone was the most commonly used antipsychotic medication followed by chlorpromazine, haloperidol, olanzapine, zuclopenthixol and quetiapine. Other commonly used medications were SSRI antidepressants such as citalopram, paroxetine and fluoxetine followed by mood stabilisers such as carbamazepine and sodium valproate. Although in a high proportion of cases carbamazepine and sodium valproate were used to treat epilepsy per se. A high proportion (45%) received more than one (polypharmacy) psychotropic medication at T1; however, this proportion decreased slightly to 41% at T2. As for antipsychotic prescribing specifically, a similar proportion received them at T1 (75%) and T2 (73%), with polypharmacy of antipsychotics remaining similar at T1 (10%) and at T2 (9%). Twenty-three per cent and 20% of patients received over 300 mg/day of chlorpromazine equivalent dose of antipsychotics at T1 and T2 respectively. However, there was an overall significant reduction in the severity of aggressive behaviour between T1 and T2. Higher doses of antipsychotic prescribing were positively correlated with more severe aggressive behaviour, physical aggression towards objects, self-injurious behaviour and increasing age. There was no significant association with other demographic variables, physical health conditions or psychiatric diagnosis. Neither was there any significant correlation between mean aggression severity score change and antipsychotic daily dose change between T1 and T2. CONCLUSIONS: To our knowledge, this is the first ever comprehensive follow-up study of use of psychotropic medications in general but antipsychotics in particular over a 6-month period in adults with ID and aggressive behaviour, in a clinic-based community setting which also compared the trajectory of severity of aggressive behaviour with that of antipsychotic medication dose. Our study shows that not only the use of psychotropic medication is common among adults with ID who attend psychiatric clinics for aggressive behaviour, the use of polypharmacy of psychotropic medications in general and high dose of antipsychotics in particular are equally prevalent. However, in some cases two antipsychotics may have been prescribed simultaneously as the psychiatrist is in the process of switching from one to another.

Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review.

BACKGROUND: ASC (autism spectrum conditions) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviours induced in animals or humans by opiate administration, including decreased socialisation, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behaviour of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason. It was therefore appropriate to reconsider the available evidence and a systematic review was undertaken. METHODS: Four electronic databases were searched for relevant journal articles. In addition, cross-referencing of pertinent reviews and a hand search for articles in major international intellectual disability (ID) journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified. We also searched databases for unpublished clinical trials to overcome publication bias. Each database was searched up to present (February 2013) with no restrictions on the date of publication. The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder as well as terms relating to opioid antagonists and specific drugs. All studies identified by the electronic database search and hand search were examined on the basis of title alone for relevance and duplication. The abstracts of the remaining papers were then scrutinised against the inclusion criteria. Where abstracts failed to provide adequate information, the full texts for these papers were obtained. All the full texts were then evaluated against the inclusion proforma. Two reviewers carried out all the stages of the process independently. The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group. Data from each study meeting the inclusion criteria were extracted on a pre-piloted data extraction form. The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials. RESULTS: 155 children participated in 10 studies; 27 received placebo. Of the 128 that received naltrexone 98 (77%) showed statistically significant improvement in symptoms of irritability and hyperactivity. Side effects were mild and the drug was generally well tolerated. CONCLUSIONS: Naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in majority of the participants. It is likely that a subgroup of children with autism and abnormal endorphin levels may respond to naltrexone and identifying the characteristics of these children must become a priority.

Are opioid antagonists effective in reducing self-injury in adults with intellectual disability? A systematic review.

BACKGROUND: Self-injury in people with intellectual disability (ID) may be due to variety of factors both environmental and biological. As the drive in UK is to manage people with ID and problem behaviours in the community, it is important to critically examine all treatment options available. As abnormalities in the endogenous opioid system may be a factor in some people with ID, we undertook a systematic review to evaluate the evidence for the effectiveness of opioid antagonists. METHODS: Four electronic databases were searched for relevant journal articles. In addition, cross-referencing of pertinent reviews and a hand search for articles in major international ID journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified. We also searched databases for unpublished clinical trials to overcome publication bias. Each database was searched up to present (February 2013) with no restrictions on the date of publication. The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder as well as terms relating to opioid antagonists and specific drugs. All studies identified by the electronic database search and hand search were examined on the basis of title alone for relevance and duplication. The abstracts of the remaining papers were then scrutinised against the inclusion criteria. Where abstracts failed to provide adequate information, the full texts for these papers were obtained. All the full texts were then evaluated against the inclusion proforma. Two reviewers carried out all the stages of the process independently. The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group. Data from each study meeting the inclusion criteria was extracted on a pre-piloted data extraction form. The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials. RESULTS: Out of 10 randomised control trials eight reported a reduction in the frequency of self-injurious behaviour. This meant that 62 participants out of 124 (50%) showed an improvement of which 61 were statistically significant. Forty-nine participants had autism. Eleven (9%) had minor side-effects. The improvement was more marked in people with severe and profound ID and was not affected by the coexistence of autism. CONCLUSIONS: This review suggests that some people respond to opioid antagonists with a reduction in self-injury but the trials do not predict who they may be. Future research may identify this sub-group when opioid antagonists may prove to be a useful addition in the pharmacotherapy of self-injury.

Validation of the Chinese version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID-CV).

BACKGROUND: An increasing number of people with intellectual disabilities (ID) are at risk of developing age-related disorders such as dementia because of a dramatic increase in life expectancy in this population in the recent years. There is no validated dementia screening instrument for Chinese people with ID. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was reported to be a valid, user-friendly, easy-to-use observer-rated instrument. It was developed in the UK and has good psychometric properties. Validation of a Chinese version of the DSQIID will facilitate its application among the Chinese population. METHOD: The DSQIID was translated into the Chinese version (DSQIID-CV). By purposive sampling, service users with ID aged 40 years or over were recruited through two large centres serving adults with ID in Hong Kong. Carers who had taken care of the participants continuously for the past 6 months were invited to complete the DSQIID-CV. All participants were examined by qualified psychiatrists to determine the presence or absence of dementia. RESULTS: Two hundred people with ID whose age ranged between 40 and 73 years (mean 51 years, SD=7.34 years) were recruited to the study. A clinical diagnosis of dementia was established in 13 participants. An overall total score of 22 as a screening cut-off provided the optimum levels of specificity (0.995) and sensitivity (0.923). The DSQIID-CV showed good internal consistency (alpha=0.945) for all its 53 items, and excellent test-retest reliability (0.978, n=46) and inter-rater reliability (1.000, n=47). Exploratory factor analysis resulted in a four-factor solution explaining 45% of the total variance. CONCLUSIONS: The DSQIID-CV is shown to have robust psychometric properties. It is the first valid and reliable dementia screening instrument for Chinese adults with ID.

16S rDNA analysis of archaea indicates dominance of Methanobacterium and high abundance of Methanomassiliicoccaceae in rumen of Nili-Ravi buffalo.

The molecular diversity of rumen methanogens was investigated using 16S rDNA gene library prepared from the rumen contents of Nili-Ravi buffaloes. Microbial genomic DNA was isolated from four adult male fistulated buffaloes and PCR conditions were set up using specific primers. Amplified product was cloned into a suitable vector, and the inserts of positive clones were sequenced. A total of 142 clones were examined, and the analysis revealed 46 species level (0.01 distance) operational taxonomic units (OTUs). Twenty six OTUs comprising 89 clones (63% of the total clones) were taxonomically assigned to Methanobacterium genus and the majority of them had highest percent identity with Methanobacterium flexile among cultured methanogens. Five OTUs comprising 27 clones (19% of total clones) were taxonomically assigned to Methanomicrobium genus and these clones showed highest sequence identity with Methanomicrobium mobile. Only two OTUs comprising 6 clones (4% of total clones) were assigned to Methanobrevibacter genus. A total of 17 clones belonging to 10 species level OTUs showed highest percent identity (ranging from 85 to 95%) with Methanomassilicoccus luminyensis and were taxonomically classified as Methanomassiliicocaceae. Out of the 142 rDNA clones, 112 clones, which constitute 79% of the total clones representing 42 OTUs, had less than 98.5% sequence identity with any of the cultured strains of methanogens and represent novel species of methanogens. This study has revealed the largest assortment of hydrogenotrophic methanogen phylotypes ever identified from the rumen of Nili-Ravi buffaloes. The study indicates that Methanobacterium is the most dominant methanogen in the rumen of Nili-Ravi buffalo. This is also the first report on the presence of methanogens phylogenetically close to M. luminyensis, an H2 dependent methylotrophic methanogen, in the rumen of buffaloes at such a high level of abundance.

MARKER ASSISTED EVALUATION OF MORPHOLOGICAL AND GENETIC ATTRIBUTES OF SUB-POPULATIONS OF NILI-RAVI BUFFALO: A VULNERABLE DAIRY TYPE RIVERINE BREED OF INDIA.

In the present study, we report the distribution of true to type and atypical Nili-Ravi buffalo, a vulnerable dairy type riverine breed of North India and its underlying genetic structure. Out of total investigated buffaloes 73.5% had bilateral wall eyes while 5.4% had unilateral wall eyes and 21.1% had no wall eyes. 41.15% of Nili-Ravi buffaloes maintained in the breeding farm were having typical true to the type characteristics (both eyes walled, white markings in forehead, muzzle/chin, all the four legs and tail) while only 28.5% of Nili-Ravi buffaloes were true to the type under field conditions. Genotypic data were generated in four groups of Nili-Ravi buffalo (FMTNR--Typical Nili-Ravi from farm; FMANR--Atypical Nili-Ravi from farm; FDTNR--Typical Nili-Ravi from field; FDANR--Atypical Nili-Ravi from field) at 16 microsatellite loci. Comparative genetic analysis of various groups of Nili-Ravi buffaloes with Murrah revealed significant between group differences with an estimated global F(ST) of 0.063. Pair-wise F(ST) values ranged from 0.003 (between FDTNR and FDANR) to 0.112 (between FMTNR and FDTNR). Phylogenetic analysis and multi-dimensional scaling revealed clustering of FDTNR and FDANR together while FMTNR and FMANR clustered separately with Murrah in between farm and field Nili-Ravi buffaloes. Based on the results, the paper also proposes three pronged strategy for conservation and sustainable genetic improvement of Nili-Ravi buffalo in India.