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Nevin Manimala Statistics

Bipolar disorder and cannabis use: A bidirectional two-sample Mendelian randomization study

Addict Biol. 2021 Mar 17:e13030. doi: 10.1111/adb.13030. Online ahead of print.

ABSTRACT

Cannabis use is associated with a number of psychiatric disorders; however, the causal nature of these associations has been difficult to establish. Mendelian randomization (MR) offers a way to infer causality between exposures with known genetic predictors (genome-wide significant single nucleotide polymorphisms [SNPs]) and outcomes of interest. MR has previously been applied to investigate the relationship between lifetime cannabis use (having ever used cannabis) and schizophrenia, depression, and attention deficit hyperactivity disorder (ADHD), but not bipolar disorder, representing a gap in the literature. We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use. Genetic instruments (SNPs) were obtained from the summary statistics of recent large genome-wide association studies (GWAS). We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use using inverse variance weighted regression, weighted median regression, and Egger regression. Genetic liability to bipolar disorder was significantly associated with an increased risk of lifetime cannabis use; however, genetic liability to lifetime cannabis use showed no association with the risk of bipolar disorder. The sensitivity analyses showed no evidence for pleiotropic effects. The present findings support a causal effect of liability to bipolar disorder on the risk of using cannabis at least once. No evidence was found for a causal effect of liability to cannabis use on the risk of bipolar disorder. These findings add important new knowledge to the understanding of the complex relationship between cannabis use and psychiatric disorders.

PMID:33733564 | DOI:10.1111/adb.13030

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Nevin Manimala Statistics

Sample size re-estimation for covariate-adaptive randomized clinical trials

Stat Med. 2021 Mar 17. doi: 10.1002/sim.8939. Online ahead of print.

ABSTRACT

Covariate-adaptive randomization (CAR) procedures have been developed in clinical trials to mitigate the imbalance of treatments among covariates. In recent years, an increasing number of trials have started to use CAR for the advantages in statistical efficiency and enhancing credibility. At the same time, sample size re-estimation (SSR) has become a common technique in industry to reduce time and cost while maintaining a good probability of success. Despite the widespread popularity of combining CAR designs with SSR, few researchers have investigated this combination theoretically. More importantly, the existing statistical inference must be adjusted to protect the desired type I error rate when a model that omits some covariates is used. In this article, we give a framework for the application of SSR in CAR trials and study the underlying theoretical properties. We give the adjusted test statistic and derive the sample size calculation formula under the CAR setting. We can tackle the difficulties caused by the adaptive features in CAR and prove the asymptotic independence between stages. Numerical studies are conducted under multiple parameter settings and scenarios that are commonly encountered in practice. The results show that all advantages of CAR and SSR can be preserved and further improved in terms of power and sample size.

PMID:33733513 | DOI:10.1002/sim.8939

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Nevin Manimala Statistics

First bite syndrome after parotidectomy: a single-centre experience

Int J Oral Maxillofac Surg. 2021 Mar 14:S0901-5027(21)00092-8. doi: 10.1016/j.ijom.2021.02.029. Online ahead of print.

ABSTRACT

The aim of this study was to investigate the prevalence of first bite syndrome (FBS) among post-parotidectomy patients and to analyse the risk factors for its occurrence. The study involved 111 adult patients operated for benign parotid tumours. After surgery, the participants were asked to assess the presence of food-related pain and the nature of the pain. Participants also answered questions on complications after parotidectomy. FBS was found in seven patients (6.3%). Sex (P=0.036) and age (P=0.002) differed significantly between patients with and without FBS. Female patients were found to be at higher risk of FBS, and the lower the patient’s age, the more likely FBS was to occur after surgery. Tumour location (P=0.002) and the occurrence of disturbing symptoms before surgery (P=0.009) had a statistically significant effect on the occurrence of FBS. A tendency towards significance for paresis of cranial nerve VII after surgery (P=0.051) was found; this complication was more frequent in the FBS patients. FBS is a rare pain syndrome that can occur after parotidectomy and should be distinguished from postoperative pain. Proper diagnosis and implementation of the appropriate treatment can significantly improve patient quality of life.

PMID:33731266 | DOI:10.1016/j.ijom.2021.02.029

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Nevin Manimala Statistics

Differentiation of Solid Pseudopapillary Tumor and Non-Functional Neuroendocrine Tumors of the Pancreas Based on CT Delayed Imaging: A Propensity Score Analysis

Acad Radiol. 2021 Mar 14:S1076-6332(21)00091-X. doi: 10.1016/j.acra.2021.02.020. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the diagnostic performance of the delayed-phase difference between tumor and pancreas for differentiating solid pseudopapillary tumors (SPTs) from non-functional neuroendocrine tumors (NF-NETs) of the pancreas.

METHODS: This retrospective review included 148 consecutive patients with SPT and 98 consecutive patients with NF-NET confirmed by pathology. Patients with SPT and NF-NET were matched via propensity score matching (PSM). All patients underwent multidetector computed tomography (MDCT). For each patient, the delayed-phase difference between the tumor and pancreas was measured, and the performance of this variable was assessed based on its discriminative ability and clinical utility.

RESULTS: After PSM, 27 patients with SPT and 27 patients with NF-NET were included in the matched analysis. There were no statistically significant differences in clinical and CT characteristics between the resulting two groups (p > 0.05). The delayed-phase difference values between the tumor and pancreas were significantly lower in patients with SPT (median: -0.45; range: -2.05 to 0.73) than in patients with NF-NET (median: 0.71; range: -1.39 to 2.38). The delayed-phase difference between tumor and pancreas had a high diagnostic accuracy (area under the curve=0.88). The best cutoff point based on maximizing the sum of the sensitivity and specificity was -0.23 (sensitivity = 88.89%; specificity = 88.89%; accuracy = 0.89).

CONCLUSIONS: The delayed-phase difference between tumor and pancreas can accurately and noninvasively differentiate SPT from NF-NET.

PMID:33731286 | DOI:10.1016/j.acra.2021.02.020

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Nevin Manimala Statistics

Multicohort Retrospective Validation of a Predictive Biomarker for Topoisomerase I Inhibitors

Clin Colorectal Cancer. 2020 Dec 10:S1533-0028(20)30167-5. doi: 10.1016/j.clcc.2020.11.005. Online ahead of print.

ABSTRACT

PURPOSE: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.

PATIENTS AND METHODS: The retrospective validation studies included a training set (n = 79) and a validation cohort (n = 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n = 176). Progression-free survival for 6 months was considered a positive response to CPT-based therapy. Formalin-fixed, paraffin-embedded slides were immunohistochemically stained with anti-phospho-specific topoI-Serine10 (topoI-pS10), quantitated, and analyzed statistically.

RESULTS: We determined a threshold of 35% positive staining to offer optimal test characteristics in GC. The GC (n = 79) training set demonstrated 76.6% (95% confidence interval, 64-86) sensitivity; 68.8% (41-88) specificity; positive predictive value (PPV) 92.5% (81-98); and negative predictive value (NPV) 42.3% (24-62). The GC validation set (n = 27) demonstrated 82.4% (56-95) sensitivity and 70.0% (35-92) specificity. Estimated PPV and NPV were 82.4% (56-95) and 70.0% (35-92) respectively. In the CRC validation set (n = 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV 70.7% (61-79); and NPV 87.0 % (77-93).

CONCLUSION: The analysis of retrospective data from patients (n = 282) provides clinical validity to our P-topoI-Dx immunohistochemical test to identify patients with disease that is most likely to respond to topoI inhibitors.

PMID:33731288 | DOI:10.1016/j.clcc.2020.11.005

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Nevin Manimala Statistics

Migrating curlews on schedule: departure and arrival patterns of a long-distance migrant depend on time and breeding location rather than on wind conditions

Mov Ecol. 2021 Mar 17;9(1):9. doi: 10.1186/s40462-021-00252-y.

ABSTRACT

BACKGROUND: Departure decisions in long-distance migratory bird species may depend on favourable weather conditions and beneficial resources at the destination location, overarched by genetic triggers. However, few studies have tried to validate the significance of these three concepts simultaneously, and long-term, high-resolution tagging datasets recording individual movements across consecutive years are scarce. We used such a dataset to explore intraspecific and intra-individual variabilities in departure and arrival decisions from/to wintering grounds in relation to these three different concepts in bird migration.

METHODS: We equipped 23 curlews (Numenius arquata) wintering in the Wadden Sea with Global Positioning System data loggers to record their spatio-temporal patterns of departure from and arrival at their wintering site, and the first part of their spring migration. We obtained data for 42 migrations over 6 years, with 12 individuals performing repeat migrations in consecutive years. Day of year of departure and arrival was related to 38 meteorological and bird-related predictors using the least absolute shrinkage and selection operator (LASSO) to identify drivers of departure and arrival decisions.

RESULTS: Curlews migrated almost exclusively to Arctic and sub-Arctic Russia for breeding. They left their wintering site mainly during the evening from mid- to late April and returned between the end of June and mid-July. There was no difference in departure times between the sexes. Weather parameters did not impact departure decisions; if departure days coincided with headwind conditions, the birds accounted for this by flying at higher altitudes of up to several kilometres. Curlews breeding further away in areas with late snowmelt departed later. Departures dates varied by only < 4 days in individual curlews tagged over consecutive years.

CONCLUSIONS: These results suggest that the trigger for migration in this long-distance migrant is largely independent of weather conditions but is subject to resource availability in breeding areas. The high intra-individual repeatability of departure days among subsequent years and the lack of relationship to weather parameters suggest the importance of genetic triggers in prompting the start of migration. Further insights into the timing of migration in immatures and closely related birds might help to further unravel the genetic mechanisms triggering migration patterns.

PMID:33731224 | DOI:10.1186/s40462-021-00252-y

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Nevin Manimala Statistics

Successful metabolic control in diabetes type 1 depends on individual neuroeconomic and health risk-taking decision endophenotypes: a new target in personalized care

Psychol Med. 2021 Mar 18:1-9. doi: 10.1017/S0033291721000386. Online ahead of print.

ABSTRACT

BACKGROUND: Neurobehavioral decision profiles have often been neglected in chronic diseases despite their direct impact on major public health issues such as treatment adherence. This remains a major concern in diabetes, despite intensive efforts and public awareness initiatives regarding its complications. We hypothesized that high rates of low adherence are related to risk-taking profiles associated with decision-making phenotypes. If this hypothesis is correct, it should be possible to define these endophenotypes independently based both on dynamic measures of metabolic control (HbA1C) and multidimensional behavioral profiles.

METHODS: In this study, 91 participants with early-stage type 1 diabetes fulfilled a battery of self-reported real-world risk behaviors and they performed an experimental task, the Balloon Analogue Risk Task (BART).

RESULTS: K-means and two-step cluster analysis suggest a two-cluster solution providing information of distinct decision profiles (concerning multiple domains of risk-taking behavior) which almost perfectly match the biological partition, based on the division between stable or improving metabolic control (MC, N = 49) v. unstably high or deteriorating states (NoMC, N = 42). This surprising dichotomy of behavioral phenotypes predicted by the dynamics of HbA1C was further corroborated by standard statistical testing. Finally, the BART game enabled to identify groups differences in feedback learning and consequent behavioral choices under ambiguity, showing distinct group choice behavioral patterns.

CONCLUSIONS: These findings suggest that distinct biobehavioral endophenotypes can be related to the success of metabolic control. These findings also have strong implications for programs to improve patient adherence, directly addressing risk-taking profiles.

PMID:33731230 | DOI:10.1017/S0033291721000386

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Nevin Manimala Statistics

Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment

Psychol Med. 2021 Mar 18:1-11. doi: 10.1017/S0033291721000763. Online ahead of print.

ABSTRACT

BACKGROUND: To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment.

METHOD: A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis.

RESULTS: Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = -0.032, nonparametric bootstrap 95% confidence interval (CI) -0.059 to -0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (β = -0.034, 95% CI -0.063 to -0.006) and regular smoking PGSs (β = -0.032, 95% CI -0.061 to -0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003-0.058).

CONCLUSIONS: Evidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.

PMID:33731234 | DOI:10.1017/S0033291721000763

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Nevin Manimala Statistics

A randomized trial of cash incentives for sexual behavior change among female sex workers in Dar es Salaam

Soc Sci Med. 2021 Mar;272:111655. doi: 10.1016/j.socscimed.2018.03.019. Epub 2018 Mar 12.

ABSTRACT

RATIONALE: Female sex workers (FSW) across the world are at high risk for HIV infection and much work is needed to scale up HIV prevention programs among this group. Conditional cash transfer (CCT) programs have been used successfully in recent years to encourage behavior change. We report the results of a CCT intervention among FSW in Tanzania.

METHODS: We conducted a randomized controlled trial (N = 100) of a CCT intervention among FSW in Dar-es-Salaam, Tanzania in 2013. A respondent-driven sampling approach recruited women and randomized them into two groups based on the value of the cash incentive ($20 vs. $40 per visit). All women received testing for 2 curable sexually transmitted infections (STIs), trichomonas and syphilis, free treatment for those STIs and counseling. Women attended study visits at 0, 2 and 4 months and were tested for STIs and received counseling at each visit. Women testing negative for both STIs at the 2- and 4-month visits received a cash reward.

RESULTS: Eighty-four women were retained in the study through all three visits. Participants reported significant reductions in the number of clients per week, and increases in the proportion of clients that they used condoms with over the course of the study. STI results showed decreases in prevalence from baseline to final study visit for syphilis and trichomonas.

CONCLUSION: While this study was not powered to determine if the incentive resulted in statistically significant increases in condom use or decreases in STI prevalence, the results show the acceptability of the intervention, the feasibility of the recruitment methods, and the ability to retain FSW participants across multiple study visits. A follow-up randomized study with a larger number of participants is planned to test the efficacy of the intervention among high-risk populations of women engaging in transactional sex.

PMID:33731255 | DOI:10.1016/j.socscimed.2018.03.019

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Nevin Manimala Statistics

Evaluation of patients with COVID-19 diagnosis for chronic diseases

Virol J. 2021 Mar 17;18(1):57. doi: 10.1186/s12985-021-01524-0.

ABSTRACT

AIM: COVID-19 is one of the most consequential pandemic in world history. Chronic diseases, which are risk factors that increase the case fatality rates, have been the leading cause of death all over the world. This study was aimed at detecting coexisting chronic diseases in patients hospitalized with a diagnosis of COVID-19.

MATERIAL AND METHOD: The study was carried out with data from 229 patients in an intensive care unit, from June 1st through June 30th. 2020. The inclusion criteria of the study was as follows: (1) having a COVID-19 diagnosis confirmed by PCR test; (2) being hospitalized in the relevant intensive care unit within the dates of the study; and (3) having their data accessible through the hospital automation system. Through literature; chronic diseases of the patients and their effects on the COVID-19 process were evaluated. Statistical analyzes were performed using the Statistical Package for Social Sciences (SPSS) version 24.0 (IBM Corp.; Armonk, NY, USA).

RESULTS: The average age of the patients studied were 61.4 years. While the average symptom duration was 8.2 days; total hospitalization period was 13.1 days. The average length of stay of patients (n = 75) who were sent to intensive care unit was 10.1. The most common chronic disease among patients was hypertension with 47.2%. This was followed by diabetes mellitus (32.8%) and heart disease (27.5%), respectively. In the population studied, cough (59.4%), fever (58.5%) and shortness of breath (45.9%) were found to be the most common symptoms. Leukopenia, impairments in liver and muscle enzymes, abnormal C-reactive protein, ferritin and d-dimer levels were the important biochemical tests.

CONCLUSION: Particular attention should be paid to the elderly COVID-19 patients with chronic diseases, especially DM, HT and cancer.

PMID:33731172 | DOI:10.1186/s12985-021-01524-0