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The Miocene beds of Kutch in India are well known for their mammalian assemblages, including the extinct ape Sivapithecus, but far less is known about the fossil squamates from this area. Although India with its over 800 reptile species is recognized as one of the global biodiversity hotspots, knowledge of past diversity and paleobiogeography of squamates on this subcontinent is very limited. We here report on new lizard finds, which have been recovered from two stratigraphic levels: the older Palasava locality (dated to the middle Miocene, ca. 14 Ma) and the younger Tapar site (late Miocene, ca. 11–10 Ma). Although fragmentarily preserved, the material described here sheds important light on the composition and paleobiogeography of squamates during the Miocene in South Asia. The older Palasava locality contains cf. Uromastyx s.l. and Varanus sp., the latter representing the oldest record of this taxon in the region of India south of the Himalayas and its occurrence here suggests a mean annual temperature not less than 15°C. The material from the younger Tapar locality consists of an unidentified acrodontan lizard, here questionably placed in agamids, and a skink. The latter shows a resemblance to mabuyines, however, the fragmentary nature of the material does not allow a precise allocation without doubts. The cosmopolitan mabuyines have been suggested to have their origin in Asia, so the potential presence of mabuyines in the Tapar locality might represent the first, but putative, Asian evidence of the occurrence of this group in the Miocene.
We report a familial cluster of 24 individuals infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The index case had a travel history and spent 24 days in the house before being tested and was asymptomatic. Physical overcrowding in the house provided a favourable environment for intra-cluster infection transmission. Restriction of movement of family members due to countrywide lockdown limited the spread in community. Among the infected, only four individuals developed symptoms. The complete genome sequences of SARS-CoV-2 was retrieved using next-generation sequencing from eight clinical samples which demonstrated a 99.99% similarity with reference to Wuhan strain and the phylogenetic analysis demonstrated a distinct cluster, lying in the B.6.6 pangolin lineage.
In this paper, a novel multiband implantable planar inverted-F antenna (PIFA) antenna based on Gosper curve fractal geometry is designed for biomedical telemetry applications. The antenna has covered four dedicated frequency bands; medical implant communication system band (MICS 402–405 MHz), industrial, scientific, and medical bands (ISM 902–928 MHz and 2.4–2.5 GHz), and wireless medical telemetry services (WMTS 1395–1400 and 1429–1432 MHz). The proposed antenna is designed on Rogers RO 3010 substrate of thickness 25 mil and volume equal to 153.67 mm3. The reflection coefficient and the radiation pattern are measured inside muscle-mimicking liquid tissue phantom. The antenna has achieved the impedance bandwidth of 126, 406, 168, and 175 MHz at MICS (403 MHz), ISM (915 MHz), WMTS (1400 MHz), and ISM (2.45 GHz) with maximum gain value −33.6, −21.04, −15.48, and −10.25 dBi, respectively. The data link range between the implantable antenna and off body antenna has been performed with −16 dBm input power. Additionally, the obtained specific absorption rate with the input of 25 μW power has also been obtained within the safety limit and hence ensures the reliability of the proposed antenna.
Coronavirus disease 2019 (COVID-19) is associated with higher rates of psychiatric morbidity due to various factors, including quarantine, social isolation, stigma, financial difficulties and direct and indirect central nervous system impact of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).
This study aimed to describe the psychiatric morbidity of patients with COVID-19 referred to liaison psychiatry services in Qatar.
This study was a retrospective review of patient records of the first 100 consecutive SARS-Cov-2 positive patients referred to liaison psychiatry services. The study was approved by the Hamad Medical Corporation Institutional Review Board (IRB) (MRC-05–072). Data were analysed using descriptive statistics.
The majority (n = 92) of 100 included patients were male and median age was 43 years. Patients were of diverse background with majority of South Asian (Indian, Pakistani, Bengali, Nepalese, and Afghan) (n = 60), followed by Qatari (n = 18) background. Mean length of hospital stay was 26.51 days.
35 patients had severe or critical COVID-19 pneumonia, and 67 had at least one underlying physical comorbidity. Significant psychosocial stressors other than positive SARS-Cov-2 status, including lockdown, quarantine, finances and relationships issues were identified in 48 patients.
A total of 35 patients had a positive past psychiatric history, out of which 17 were on maintenance psychotropic medications. Insomnia was the commonest psychiatric symptom (n = 65), followed by anxiety (n = 52), agitation (n = 42), depression (n = 39), changes in appetite (n = 32) and irritability (n = 30). The principal psychiatric diagnoses made were delirium (n = 29), acute stress reaction or adjustment disorder (n = 25), depression (n = 16), mania (n = 15), anxiety (n = 14), non-affective psychosis (n = 13), and dementia (n = 6). Approximately half of the patients with mania or non-affective psychosis had it as their first-onset disorder.
SARS-CoV-2, in both symptomatic and asymptomatic patients, is associated with a wide range of psychiatric morbidity which emphasizes clinicians’ vigilance for psychiatric symptoms. Insomnia was the commonest neuropsychiatric symptom which may have clinical practice and potential preventive strategies implications.
Delirium, the commonest diagnosis in the study carries high morbidity and mortality and may reflect SARS-Cov-2 propensity to affect the brain directly and indirectly through a cytokine storm, organ failure, and prothrombotic state. Patients can also present with new-onset mania or non-affective psychosis. It is noteworthy that about two-thirds of the patients had no past psychiatric history.
This study, along with expanding body of evidence may assist with resource allocation and liaison psychiatry services planning. It also underscores the importance of designing future studies to better understand longer-term psychiatric sequelae of COVID-19.
Objective of the study was to assess subjective global nutritional assessment (SGNA) in children with chronic liver diseases (CLD). Children aged 3 months to 18 years with CLD were prospectively enrolled (January 2016 to October 2018). SGNA was performed as per validated pro forma for children. Nutritional categories were categorised into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). Agreement between SGNA and anthropometric measures, prediction of morbidity and death or liver transplantation (LT) at 1-year post-enrolment by SGNA and inter-observer reliability of SGNA were assessed. Ninety-two subjects were enrolled, median age 23·5 (3–216) months. SGNA classified 47 patients (51·1 %) in group A, 26 (28·3 %) in group B and 19 (20·6 %) in group C. Kendall coefficients disclosed significant association of SGNA with all anthropometric measurements, greatest with weight for age (r = −0·637), height for age (r = −0·581) and mid-arm fat area (r = −0·449). At 12 months follow-up, twenty children died and four received LT. A significantly higher number of children with malnutrition (groups B and C) had poor outcome (OR 6·74 (95 % CI 2·21, 20·55), P = 0·001), increased risk of hospital readmission (OR 12·2 (95 % CI 4·60, 35·88), P = 0·001), higher rate of infectious complications (OR 22·68 (95 % CI 7·29, 70·53), P < 0·0001) and lower median survival with native liver (Log Rank < 0·001) as compared with group A. Inter-observer agreement in assessment of SGNA was good (90·2 %). SGNA, in contrast to anthropometric measures, is a better nutritional assessment tool. It is reliable, comprehensive and predicts poor outcome in childhood CLD.
Soil and nutrients losses due to soil erosion are detrimental to crop production, especially in the hilly terrains. An experiment was carried out in three consecutive cropping seasons (2012–2015) with four treatments: sole maize; sole maize with plastic mulch; maize and cowpea under plastic mulching; and maize and soybean under plastic mulching in randomized block design (RBD) to assess their impact on productivity, profitability, and resource (rainwater, soil, and NPK nutrients) conservation in the Indian sub-Himalayan region. The plot size was 9 × 8.1 m with 2% slope, and runoff and soil loss were measured using a multi-slot devisor. The results showed that mean runoff decreased from 356 mm in sole maize with plastic mulch plots to 229 mm in maize + cowpea intercropping with plastic mulch, representing a reduction of 36% and corresponding soil loss reduction was 41% (from 9.4 to 5.5 t ha−1). The eroded soil exported a considerable amount of nitrogen (N) (13.2–31.4 kg ha−1), phosphorous (P) (0.5–1.7 kg ha−1), and potassium (K) (9.9–15.6 kg ha−1) and was consistently lower in maize + cowpea intercropping. The maize equivalent yield (MEY) was significantly higher in maize + cowpea with plastic mulch intercropping than the other treatments. These results justify the need to adopt maize with alternate legume intercrops and plastic mulch. This strategy must be done in a way guaranteeing high yield stability to the smallholder farmers of the Indian sub-Himalayan region.
The primary purpose of this study is to examine changes in socio-economic inequality in nutritional status (stunting and underweight) among children in Empowered Action Group (EAG) states.
The study is based on the most recent two wave’s cross-sectional data from the National Family Health Survey (NFHS) conducted in 2005–2006 (NFHS-3) and 2015–2016 (NFHS-4). The study used height-for-age (stunting) and weight-for-age (underweight) of children as anthropometric indicators.
EAG states including Bihar, Chhattisgarh, Jharkhand, Madhya Pradesh, Odisha, Rajasthan, Uttarakhand and Uttar Pradesh in India.
The study includes a total of 11 858 (NFHS-3) and 92 630 (NFHS-4) children under 5 years of age.
The socio-economic inequality in stunting remained unchanged in all EAG states. At the same time, the inequality in underweight decreased during 2005–2016. On decomposing, the factors contributing to socio-economic inequality revealed that household wealth index, mother’s education and mother’s nutritional status were the largest contributors to stunting (47 %, 24 % and 8 %) and underweight (51 %, 21 % and 16 %), respectively, in 2015–2016.
The study concluded the socio-economic inequality in underweight among children under 5 years of age increased over the years in EAG states in India. Altogether, household wealth index, mother’s education and mother’s nutritional status contributed to nearly 80 % to inequality in stunting and 90 % to inequality in underweight in 2015–2016. Hence, efforts should be made to minimise the socio-economic inequality in the nutritional status of children, particularly in EAG states in India.
Radiation therapy has historically used margins for target volume to ensure dosimetric planning criteria. The size of margin for a given treatment site is still uncertain particularly for moving targets along with set-up variations leading to a fuzziness of target volume. In this study, we have estimated the dosimetric benefit of normal structures using biological-based optimal margins. The treatment margins are derived by knowledge-based fuzzy logic technique which is considering the radiotherapy uncertainties in treatment planning.
Materials and methods:
All treatment plans were performed using stepped increments of asymmetric margins to estimate prostate radiobiological indices such as tumour control probability (TCP) and normal tissue complication probability (NTCP). An absolute NTCP of 5% was considered to be the maximum acceptable value while TCP of 85% was considered to be the minimal acceptable limit for each volumetric modulated arc therapy (VMAT) plan of localised prostate cancer radiotherapy. Results were used to formulate rules and membership functions for Mamdani-type fuzzy inference system (FIS). In implementing the rules for the fuzzy system for ΔNTCP values above 10%, the PTV margin was not permitted to exceed 5 mm to avoid rectal complications due to margin selection. The new margins were applied in VMAT planning of prostate cancer for standard displacement errors. The dosimetric results of normal tissue predictors were estimated such as organ mean doses, rectum V60 (volume receiving 60 Gy), bladder V65 (volume receiving 65 Gy) and other clinically significant dose–volume indicators and compared with VMAT plans using current margin formulations.
Dosimetric results compared well to the results obtained by current techniques. Good agreement was obtained between proposed fuzzy model margins and currently used margins in lower error magnitude, but significant results were observed at higher error magnitude when organ toxicity concerned without compromising the target volumes.
The new margins may be helpful to estimate possible outcomes of normal tissue complications and thus may improve complication free survival particularly when organ motion errors are inevitable, case by case.
Background: Healthcare-associated infections (HAIs) are a major global threat to patient safety. Systematic surveillance is crucial for understanding HAI rates and antimicrobial resistance trends and to guide infection prevention and control (IPC) activities based on local epidemiology. In India, no standardized national HAI surveillance system was in place before 2017. Methods: Public and private hospitals from across 21 states in India were recruited to participate in an HAI surveillance network. Baseline assessments followed by trainings ensured that basic microbiology and IPC implementation capacity existed at all sites. Standardized surveillance protocols for central-line–associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) were modified from the NHSN for the Indian context. IPC nurses were trained to implement surveillance protocols. Data were reported through a locally developed web portal. Standardized external data quality checks were performed to assure data quality. Results: Between May 2017 and April 2019, 109 ICUs from 37 hospitals (29 public and 8 private) enrolled in the network, of which 33 were teaching hospitals with >500 beds. The network recorded 679,109 patient days, 212,081 central-line days, and 387,092 urinary catheter days. Overall, 4,301 bloodstream infection (BSI) events and 1,402 urinary tract infection (UTI) events were reported. The network CLABSI rate was 9.4 per 1,000 central-line days and the CAUTI rate was 3.4 per 1,000 catheter days. The central-line utilization ratio was 0.31 and the urinary catheter utilization ratio was 0.57. Moreover, 3,542 (73%) of 4,742 pathogens reported from BSIs and 868 (53%) of 1,644 pathogens reported from UTIs were gram negative. Also, 1,680 (26.3%) of all 6,386 pathogens reported were Enterobacteriaceae. Of 1,486 Enterobacteriaceae with complete antibiotic susceptibility testing data reported, 832 (57%) were carbapenem resistant. Of 951 Enterobacteriaceae subjected to colistin broth microdilution testing, 62 (7%) were colistin resistant. The surveillance platform identified 2 separate hospital-level HAI outbreaks; one caused by colistin-resistant K. pneumoniae and another due to Burkholderia cepacia. Phased expansion of surveillance to additional hospitals continues. Conclusions: HAI surveillance was successfully implemented across a national network of diverse hospitals using modified NHSN protocols. Surveillance data are being used to understand HAI burden and trends at the facility and national levels, to inform public policy, and to direct efforts to implement effective hospital IPC activities. This network approach to HAI surveillance may provide lessons to other countries or contexts with limited surveillance capacity.
Reports of psychiatric morbidity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tend to be limited by geography and patients’ clinical status. Representative samples are needed to inform service planning and research.
To describe the psychiatric morbidity associated with SARS-CoV-2 infection (confirmed by real-time polymerase chain reaction) in referrals to a consultation-liaison psychiatry service in Qatar.
Retrospective review of 50 consecutive referrals.
Most patients were male. Median age was 39.5 years. Thirty-one patients were symptomatic (upper respiratory tract symptoms or pneumonia) for coronavirus disease 2019 (COVID-19) and 19 were asymptomatic (no characteristic physical symptoms of COVID-19 infection). Seventeen patients (34%) had a past psychiatric history including eight with bipolar I disorder or psychosis, all of whom relapsed. Thirty patients (60%) had physical comorbidity. The principal psychiatric diagnoses made by the consultation-liaison team were delirium (n = 13), psychosis (n = 9), acute stress reaction (n = 8), anxiety disorder (n = 8), depression (n = 8) and mania (n = 8). Delirium was confined to the COVID-19 symptomatic group (the exception being one asymptomatic patient with concurrent physical illness). The other psychiatric diagnoses spanned the symptomatic and asymptomatic patients with COVID. One patient with COVID-19 pneumonia experienced an ischaemic stroke. Approximately half the patients with mania and psychosis had no past psychiatric history. Three patients self-harmed. The commonest psychiatric symptoms were sleep disturbance (70%), anxiety (64%), agitation (50%), depressed mood (42%) and irritability (36%).
A wide range of psychiatric morbidity is associated with SARS-CoV-2 infection and is seen in symptomatic and asymptomatic individuals. Cases of psychosis and mania represented relapses in people with schizophrenia and bipolar disorder and also new onset cases.
This study assessed the tobacco smoking-associated risk for tuberculous pleural effusion (TPE) in India. Ninety-two patients with TPE and 184 controls were randomly selected and assessed regarding their tobacco-smoking status and type, quantity and duration of tobacco used. Odds ratios (ORs) for the association of smoking cigarette, beedi and cigarette or beedi with TPE were 19.22 (p < 0.0001), 2.89 (p = 0.0006) and 4.57 (p < 0.0001) respectively. ORs for developing TPE increased with an increase in beedi/cigarette consumption, duration and pack years of smoking (p < 0.001 each). TPE was significantly associated with confounding risk factors viz., regular alcohol use (OR = 1.89, p = 0.019), history of contact with tuberculosis (TB) patient (OR = 8.07, p < 0.0001), past history of TB (OR = 22.31, p < 0.0001), family history of TB (OR = 9.05, p = 0.0002) and underweight (OR = 3.73, p = 0.0009). Smoking (OR = 3.07, p < 0.001), regular alcohol use (OR = 2.10, p = 0.018), history of contact with TB patient (OR = 4.01, p = 0.040), family history of TB (OR = 10.80, p = 0.001) and underweight (OR = 5.04, p < 0.001) were independently associated with TPE. Thus, both cigarette- and beedi-smoking have a significant association with TPE. The risk for TPE in tobacco smokers is dose- and duration-dependent.
The intensity of turbidite sedimentation over long timescales is driven by sea-level change, tectonically driven rock uplift and climatically modulated sediment delivery rates. This study focuses on understanding the effect of sea-level fluctuations and climatic variability on grain-size variations. The grain size and environmental magnetic parameters of Arabian Sea sediments have been documented using 203 samples, spanning the last 200 ka, obtained from International Ocean Discovery Program (IODP) Site U1457. Grain-size end-member modelling suggests that between ~200 and 130 ka there was an increase in the coarse silt fraction caused by sediment transport following reworking of the Indus Fan and development of deep-sea canyons. The sediment size and enhanced magnetic susceptibility indicate a dominant flux of terrestrial sediments. Sedimentation in the distal Indus Fan at c. 200–130 ka was driven by a drop in sea level that lowered the base level in the Indus and Narmada river systems. The low sea-stand caused incision in the Indus delta, canyons and fan area, which resulted in the transportation of coarser sediment at the drilling site. Magnetic susceptibility and other associated magnetic parameters suggest a large fraction of the sediment was supplied by the Narmada River during ~200–130 ka. Since ~130 ka, clay-dominated sedimentation is attributed to the rise in sea level due to warm and wet climate.
Upper water column dynamics in the eastern Arabian Sea were reconstructed in order to investigate changes in the activity of the South Asian / Indian monsoon during the early Pleistocene (c. 1.5–2.7 Ma). We used planktic foraminiferal assemblage records combined with isotopic (δ18O and δ13C) data, Mg/Ca-based sea surface temperatures and seawater δ18O records to estimate changes in surface water conditions at International Ocean Discovery Program (IODP) Site U1457. Our records indicate two distinct regimes of monsoon-induced changes in upper water structure during the periods c. 1.55–1.65 Ma and c. 1.85–2.7 Ma. We infer that a more stratified upper water column and oligotrophic mixed layer conditions prevailed during the period 1.85–2.7 Ma, which may be due to overall weaker South Asian / Indian winter (NE) and summer (SW) monsoon circulations. The period 1.55–1.65 Ma was characterized by enhanced eutrophication of the mixed layer, which was probably triggered by intensified winter (NE) monsoonal winds. The long-term trend in hydrographic changes during 1.55–1.65 Ma appears to be superimposed by short-term variations, probably reflecting glacial/interglacial changes. We suggest that an intensification of the South Asian / Indian winter monsoon circulation occurred between ∼1.65 Ma and 1.85 Ma, which is most likely due to the development of strong meridional and zonal atmospheric circulations (i.e. Walker Circulation and Hadley Circulation) because of strong equatorial East–West Pacific temperature gradients.
Tardive dyskinesia (TD) results from exposure to dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics. Clinicians commonly manage TD by reducing the dose of or stopping the causative agent; however, this may cause psychiatric relapse and worsen quality of life. In the 12-week ARM-TD and AIM-TD trials, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores versus placebo and was generally well tolerated, regardless of baseline DRA use or comorbidities.
To evaluate the impact of underlying disease and current DRA use on efficacy and safety of long-term therapy of deutetrabenazine in patients with TD.
Patients with TD who completed ARM-TD or AIM-TD were eligible to enter this open-label, single-arm, long-term extension after completing the 1-week washout period and final evaluation in the blinded portion of the trial. Change in AIMS scores from baseline to Week 54 and patients “Much Improved” or “Very Much Improved” (treatment success) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) at Week 54 were analyzed by baseline psychiatric illness type, including mood disorders (bipolar disorder/depression/other) or psychotic disorders (schizophrenia/schizoaffective disorder), and presence or absence of current DRA use.
At Week 54, meaningful improvements from baseline in mean (standard error) AIMS scores were observed for patients with baseline mood disorders (–5.2[0.93]) and psychotic disorders (–5.0[0.63]), and in patients currently using DRAs (–4.6[0.54]) or not using DRAs (–6.4[1.27]). Most patients with mood disorders (73%) and psychotic disorders (71%) were “Much Improved” or “Very Much Improved” on CGIC at Week 54, similar to patients currently using (71%) or not using (74%) DRAs. The majority of patients with mood disorders (62%) and psychotic disorders (57%), as well as patients currently using (58%) or not using (63%) DRAs, were also “Much Improved” or “Very Much Improved” on PGIC at Week 54. Prior treatment in ARM-TD and AIM-TD did not impact the long-term treatment response. Underlying psychiatric disorder and concomitant DRA use did not impact the occurrence of adverse events (AEs). The frequencies of dose reductions, dose suspensions, and withdrawals due to AEs were low, regardless of baseline psychiatric comorbidities and DRAuse.
Long-term deutetrabenazine treatment demonstrated meaningful improvements in abnormal movements in TD patients, which were recognized by clinicians and patients, regardless of underlying psychiatric illness or DRAuse.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant improvements in centrally read Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with PBO and was generally well tolerated.
To evaluate the long-term efficacy of DTB in an open-label safety study following double-blind treatment using site-rated efficacy measures: AIMS, the Clinical Global Impression of Change (CGIC) and the Patient Global Impression of Change (PGIC), which may be used in real-world clinical practice settings.
Patients with TD who completed the parent studies were eligible to enter this open-label, long-term extension (OLE) after completing the 1-week washout period and final evaluation in the blinded portion of the trial. This extension comprised a 6-week titration period followed by a long-term maintenance phase. Patients began DTB at 12mg/day, titrating up to a maximum total dose of 48mg/day based on dyskinesia control and tolerability. Efficacy endpoints included in this analysis are the change in site-rated AIMS score (items 1–7) from parent study baseline, and the proportion of patients who were “Much Improved” or “Very Much Improved” (treatment success) on the CGIC and PGIC from OLE baseline.
At the end of the parent studies (Week 12), patients treated with DTB had experienced greater mean (standard error) improvements in site-rated AIMS score (–5.0[0.40]) than patients given PBO (–3.2[0.47]). With long-term DTB treatment, both groups experienced improvements in site-rated AIMS scores (prior DTB, –7.9[0.62]; prior placebo, –6.6[0.64]) compared with parent study baseline. Similarly, at the end of the parent studies, a greater proportion of patients treated with DTB had treatment success on the CGIC (DTB, 51%; PBO, 32%) and the PGIC (DTB, 46%; PBO: 33%); whereas at Week 54 of the OLE study, treatment success on CGIC and PGIC were similar in both the CGIC (prior DTB: 66%; prior PBO: 68%) and PGIC (prior DTB: 62%; prior PBO: 62%) groups. DTB was generally well tolerated.
Patients treated with DTB showed improvements in abnormal movements, as measured by site-rated AIMS, CGIC, and PGIC scores, which may be used in real-world clinical practice settings. These results corroborate the previously reported efficacy of DTB as observed in the 12-week, double-blind ARM-TD and AIM-TD trials, in which central raters were used to evaluate AIMS scores.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Week 54 open-labelresults are reported in this interim analysis.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safetymeasures included incidence of adverse events (AEs), serious AEs (SAEs), drug-related AEs, and AEs leading to withdrawal, dose reduction, or dose suspension. This analysis reports results up to Week 54.
304 patients enrolled in the extension study. There were 215 patient-years of exposure in this analysis, and exposure-adjusted incidence rates (EAIRs) of AEs (incidence/patient-years) were comparable to or lower than those observed with short-term deutetrabenazine treatment and placebo. The frequency of SAEs (EAIR 0.14) was similar to rates observed with short-termplacebo (EAIR 0.33) and deutetrabenazine (EAIR range 0.06–0.33) treatment. AEs leading to study discontinuation (EAIR 0.08), dose reduction (EAIR 0.17), and dose suspension (EAIR 0.09) were uncommon.
Long-term treatment with deutetrabenazine was generally safe and well tolerated in patients with TD, and did not result in cumulative toxicity.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated.
To evaluate the efficacy and safety of long-term deutetrabenazine therapy in patients with TD.
Patients with TD who completed the ARM-TD or AIM-TD studies were eligible to enter this open-label, single-arm, long-term safety study after they completed the 1-week washout period and final evaluation in the blinded portion of the trial. Efficacy endpoints included the change in AIMS score from baseline, and treatment success (defined as “much improved” or “very much improved”) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC). This analysis reports results up to Week 54.
304 patients enrolled in the extension study. At Week 54, the mean (standard error) change in AIMS score was –5.1 (0.52). After 6 weeks of deutetrabenazine treatment, the proportion of patients who achieved treatment success was 58% per the CGIC and 53% per the PGIC, and by Week 54 was 72% per the CGIC and 59% per the PGIC, thus demonstrating maintenance or enhancement of benefit over time. Deutetrabenazine was well tolerated for up to 54 weeks, and compared with the ARM-TD and AIM-TD studies, no new safety signals were detected.
54 weeks of deutetrabenazine treatment was generally efficacious, safe, and well tolerated in patients with TD.
Presented at: The American Psychiatric Association 2017 Annual Meeting; May 20–24, 2017; San Diego, California, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).
To evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.
ARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.
At Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).
Deutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.
Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.
These studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
We reconstruct centennial scale quantitative changes in surface seawater temperature (SST), evaporation-precipitation (from Mg/Ca and δ18O of surface dwelling planktic foraminifera), productivity (from relative abundance of Globigerina bulloides), carbon burial (from %CaCO3 and organic carbon [%Corg]) and dissolved oxygen at sediment-water interface, covering the entire Holocene, from a core collected from the eastern Arabian Sea. From the multi-proxy record, we define the timing, consequences and possible causes of the mid-Holocene climate transition (MHCT). A distinct shift in evaporation-precipitation (E-P) is observed at 6.4 ka, accompanied by a net cooling of SST. The shift in SST and E-P is synchronous with a change in surface productivity. A concurrent decrease is also noted in both the planktic foraminiferal abundance and coarse sediment fraction. A shift in carbon burial, as inferred from both the %CaCO3 and %Corg, coincides with a change in surface productivity. A simultaneous decrease in dissolved oxygen at the sediment-water interface, suggests that changes affected both the surface and subsurface water. A similar concomitant change is also observed in other cores from the Arabian Sea as well as terrestrial records, suggesting a widespread regional MHCT. The MHCT coincides with decreasing low-latitude summer insolation, perturbations in total solar intensity and an increase in atmospheric CO2.