Nevin Manimala

J Psychiatr Res. 2022 Jan 18;148:1-8. doi: 10.1016/j.jpsychires.2022.01.031. Online ahead of print.

ABSTRACT

Although preliminary neuroimaging research suggests that patients with hoarding disorder (HD) show widespread abnormal task-related activity in the brain, there has been no research on alterations in the white matter tracts in these patients. The aim of this study was to investigate the characteristics of the major white matter tracts in patients with HD. Tract-based spatial statistics were used to search for white matter tract abnormalities throughout the brain in 25 patients with HD and 36 healthy controls. Post hoc analysis of regions of interest was performed to detect correlations with clinical features. Compared with the controls, patients with HD showed decreased fractional anisotropy and increased radial diffusivity in anatomically widespread white matter tracts. Post hoc analysis of regions of interest revealed a significant negative correlation between the severity of hoarding symptoms and fractional anisotropy in the left anterior limb of the internal capsule and a positive correlation between the severity of these symptoms and radial diffusivity in the right anterior thalamic radiation. Patients with HD showed a broad range of alterations in the frontal white matter tracts, including the frontothalamic circuit, frontoparietal network, and frontolimbic pathway. The findings of this study indicate associations between frontal white matter abnormalities related to the severity of hoarding symptoms in HD and the cortical regions involved in cognitive dysfunction. The insights provided would be useful for understanding the neurobiological basis of HD.

PMID:35081485 | DOI:10.1016/j.jpsychires.2022.01.031

J Neurol Sci. 2022 Jan 6;434:120142. doi: 10.1016/j.jns.2022.120142. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH).

METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events.

RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups.

CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

PMID:35081458 | DOI:10.1016/j.jns.2022.120142

J Clin Epidemiol. 2022 Jan 23:S0895-4356(22)00021-X. doi: 10.1016/j.jclinepi.2022.01.014. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the prevalence of poor interpretation practices, such as conflating evidence of absence with absence of evidence and over-emphasis of statistical non-significance in abstract conclusions, in a sample of randomised controlled trials (RCTs) with non-statistically significant primary outcomes published after the 2016 American Statistical Association statement on the interpretation of p-values.

DESIGN AND SETTING: Review of 50 two-arm individually randomised superiority trials with non-statistically significant results in four high impact journals published between 2017 and 2020, to determine the proportion that conclude evidence of no impact (thus, likely conflating evidence of absence with absence of evidence) or place emphasis on statistical non-significance (technically correct but arguably uninformative) in the abstract conclusion.

RESULTS: Of the 50 RCTs with non-statistically significant results for primary outcomes, 28 (56%) of abstract were classified as concluding there was no difference between the two treatments; 19 (38%) placed an over-emphasis on statistical significance; only one acknowledged any uncertainty and the remaining 2 (4%) concluded that one treatment was more effective. Only four studies provided any justification for a finding of no difference, for example that the confidence interval gave no support to values of importance.

CONCLUSIONS: RCTs with non-statistically significant primary outcomes almost always present their conclusion in the abstract as evidence of no impact or ambiguously as “not statistically significant” without giving due attention to values supported by the confidence interval.

PMID:35081450 | DOI:10.1016/j.jclinepi.2022.01.014

J Pain Symptom Manage. 2022 Jan 23:S0885-3924(22)00034-3. doi: 10.1016/j.jpainsymman.2022.01.013. Online ahead of print.

ABSTRACT

CONTEXT: The optimal strategy for implementing mortality-predicting algorithms to facilitate clinical care, prognostic discussions, and palliative care interventions remains unknown.

OBJECTIVES: To develop and validate a real-time predictive model for 180-day mortality using routinely available clinical and laboratory admission data and determine if palliative care exposure varies with predicted mortality risk.

METHODS: Adult admissions between 10/1/2013 and 10/1/2017 were included for the model derivation. A separate cohort was collected between 1/1/2018 and 7/31/2020 for validation. Patients were followed for 180 days from discharge, and logistic regression with selected variables was used to estimate patients’ risk for mortality.

RESULTS: In the model derivation cohort, 7963 events of 180-day mortality (4.5% event rate) were observed. Median age was 53.0 (IQR 24.0-66.0) with 92,734 females (52.5%). Variables with strongest association with 180-day mortality included: Braden Score (OR 0.83; 95% CI 0.82-0.84); admission Do Not Resuscitate orders (OR 2.61; 95% CI 2.43-2.79); admission service and admission status. The model yielded excellent discriminatory ability in both the derivation (c-statistic 0.873; 95% CI 0.870-0.877; Brier score 0.04) and validation cohorts (c-statistic 0.844; 95% CI 0.840-0.847; Brier score 0.072). Inpatient palliative care consultations increased from 3% of minimal-risk encounters to 41% of high-risk encounters (p<0.01).

CONCLUSION: We developed and temporally validated a predictive mortality model for adults from a large retrospective cohort, which helps quantify the potential need for palliative care referrals based on risk strata. Machine learning algorithms for mortality require clinical interpretation, and additional studies are needed to design patient-centered and risk-specific interventions.

PMID:35081441 | DOI:10.1016/j.jpainsymman.2022.01.013

J Dent. 2022 Jan 23:104050. doi: 10.1016/j.jdent.2022.104050. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the performance of a novel resin-modified glass-ionomer cement (pRMGIC) bonded to various tooth tissues after two-time intervals.

METHODS: 192 sound human molars were randomly assigned to 3 groups (n=64): sound enamel, demineralised enamel, sound dentine. Sixty-four teeth with natural carious lesions including caries-affected dentine (CAD) were selected. All substrates were prepared, conditioned and restored with pRMGIC (30% ethylene glycol methacrylate phosphate (EGMP, experimental), Fuji II LC (control), Fuji IX, and Filtek™ Supreme with Scotchbond ^TM Universal Adhesive. Shear bond strength (SBS) was determined after 24 h and three months storage in SBF at 37°C. The debonded surfaces were examined using stereomicroscopy and scanning electron microscopy (SEM). Multivariate Analysis of Variance (MANOVA), Bonferroni post hoc tests (alpha=0.05) and independent T-tests were used for multifactorial data analysis.

RESULTS: The hydrophilicity and functionality of EGMP enhanced the bond strength of the pRMGIC to different substrates after 24 h and 3 months as compared to F2LC (p<0.05). Adhesive failures were found to decrease with pRMGIC and integration into exposed enamel prisms and dentine tubules was observed with SEM. Ageing enhanced bond strength of pRMGIC to all substrates but was statistically significantly only in sound dentine. The SBS of pRMGIC was higher with sound vs. demineralised enamel at both time periods (p<0.001), while it was higher to CAD initially and to sound dentine post-storage (p=0.004).

CONCLUSIONS: pRMGIC exhibited enhanced bonding performance to various tooth tissues with an ability to seal exposed enamel prisms and dentine tubules.

CLINICAL SIGNIFICANCE: pRMGIC is a promising material exhibiting long-lasting bonded-tooth interfaces, for its use in minimally invasive reparative techniques.

PMID:35081422 | DOI:10.1016/j.jdent.2022.104050

Urology. 2022 Jan 23:S0090-4295(22)00070-X. doi: 10.1016/j.urology.2022.01.020. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine practice-level variation in the management of MRI PI-RADS 3 lesions in men with favorable-risk prostate cancer (FRPC) considering or on active surveillance (AS).

METHODS: We reviewed the MUSIC registry for FRPC men (GG1 and low-volume GG2) undergoing MRI from 1/2013-3/2020. The primary outcome was to assess practice-level variation in time from MRI to biopsy and MRI to treatment for PI-RADS 3 lesions. Both MRIs obtained after the diagnostic biopsy and while on AS were included. The Kaplan-Meier method was used to estimate biopsy-free survival for time from MRI to surveillance biopsy and multivariable Cox proportional hazards models identified clinical and demographic factors associated with time obtaining a biopsy after finding PI-RADS 3 lesions.

RESULTS: We identified 3,172 FRPC men with a MRI, of whom 473 had a PI-RADS 3. There was significant practice-level variation in biopsy rates among patients with PI-RADS 3 MRI results (log-rank test, p<0.001), with biopsy-free probability at 6 months ranging from 28%-69% (median: 59%). We were unable to identify factors with significant associations with time to biopsy. Conversely, there was less variation in time from PI-RADS 3 to treatment (log-rank test, p=0.2), while several clinical factors had statistically-significant associations: age(p=0.018), PSA-Density 0.1-0.2(p=0.035), ISUP-GG 2(p=0.002), and number of positive cores(p<0.001), as expected.

CONCLUSION: Urology practice, rather than GG or extent of biopsy positivity, is the largest factor affecting the decision for biopsy of PI-RADS 3 lesions in FRPC men considering or on AS. Future work to assist with decision-making and reduce variability is needed.

PMID:35081398 | DOI:10.1016/j.urology.2022.01.020

Annu Rev Phys Chem. 2022 Jan 26. doi: 10.1146/annurev-physchem-090519-045916. Online ahead of print.

ABSTRACT

We review a suite of stochastic vector computational approaches for studying the electronic structure of extended condensed matter systems. These techniques help reduce algorithmic complexity, facilitate efficient parallelization, simplify computational tasks, accelerate calculations, and diminish memory requirements. While their scope is vast, we limit our study to ground-state and finite temperature density functional theory (DFT) and second-order perturbation theory. More advanced topics, such as quasiparticle (charge) and optical (neutral) excitations and higher-order processes, are covered elsewhere. We start by explaining how to use stochastic vectors in computations, characterizing the associated statistical errors. Next, we show how to estimate the electron density in DFT and discuss highly effective techniques to reduce statistical errors. Finally, we review the use of stochastic vector techniques for calculating correlation energies within the second-order Møller-Plesset perturbation theory and its finite temperature variational form. Example calculation results are presented and used to demonstrate the efficacy of the methods. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:35081326 | DOI:10.1146/annurev-physchem-090519-045916

Annu Rev Phys Chem. 2022 Jan 26. doi: 10.1146/annurev-physchem-082620-021809. Online ahead of print.

ABSTRACT

This review focuses on a recent class of path-integral-based methods that simulate nonadiabatic dynamics in the condensed phase using only classical molecular dynamics trajectories in an extended phase space. Specifically, a semiclassical mapping protocol is used to derive an exact, continuous, Cartesian variable path-integral representation for the canonical partition function of a system in which multiple electronic states are coupled to nuclear degrees of freedom. Building on this exact statistical foundation, multistate ring polymer molecular dynamics methods are developed for the approximate calculation of real-time thermal correlation functions. The remarkable promise of these multistate ring polymer methods, their successful applications, and their limitations are discussed in detail.Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:35081325 | DOI:10.1146/annurev-physchem-082620-021809

N Engl J Med. 2022 Jan 26. doi: 10.1056/NEJMoa2116414. Online ahead of print.

ABSTRACT

BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.

METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×10¹⁰ virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29.

RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.

CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

PMID:35081293 | DOI:10.1056/NEJMoa2116414

J Clin Psychiatry. 2022 Jan 25;83(1):22f14388. doi: 10.4088/JCP.22f14388.

ABSTRACT

During the past decade, nearly a dozen small and large, prospective and retrospective observational studies examined cognitive neurodevelopmental outcomes in childhood after gestational exposure to antidepressant drugs. Many of the studies found that exposure was associated with poorer outcomes on measures of language, cognition, intellectual skills, and academic performance, but, in most instances, the association appeared to be more related to maternal depression during pregnancy and other confounds than to antidepressant use during pregnancy. A large new population-based observational study specifically examined language and mathematics performance in serial, nationally standardized tests. The study found that, in fully adjusted analyses, in children and adolescents aged 9-15 years, a history of gestational exposure to antidepressant drugs was associated with a small (by about 2 out of 100 points) but statistically significantly poorer performance in mathematics but not in language. The findings were consistent though attenuated in a large number of important and appropriate sensitivity analyses, some of which adjusted for confounding in additional ways. The body of literature reviewed suggests that prenatal antidepressant exposure is indeed associated with cognitive neurodevelopmental deficits and that the deficits are attenuated or eliminated by adjustment for maternal depression and other confounds. It is suggested that the deficits that remain despite adjustment may be due to residual confounding from unmeasured behavioral and internal environment variables associated with untreated maternal depression. Thus, prenatal antidepressant exposure may merely be a marker rather than the cause of cognitive neurodevelopmental deficits. Whereas the literature in the field does not drive a case for withholding antidepressants from depressed pregnant women, decision-making must remain a shared process.

PMID:35081278 | DOI:10.4088/JCP.22f14388