Nevin Manimala

Psychoneuroendocrinology. 2022 Mar 9;139:105717. doi: 10.1016/j.psyneuen.2022.105717. Online ahead of print.

ABSTRACT

Adverse childhood experiences (ACEs) have been associated with unfavorable health outcomes throughout the life up to old age. Mechanisms through which ACEs impact later life health are still not entirely clear. There is growing evidence for the idea that alterations in the hypothalamic pituitary adrenal (HPA) axis might cause the effects of ACEs on later health consequences. Only few studies have investigated associations between ACEs and diurnal HPA axis functioning in older adults. Therefore, we investigated the impact of type and timing of ACEs linked to flight of war on diurnal HPA axis activity in a sample of East Prussian World War II refugees aged 74-91 years. We calculated a dichotomous variable according to the (minimum) age at trauma: early ACE (eACE; 0-5 years) and late ACE (lACE; 6-17 years). Multiple linear regression analysis using different ACEs linked to flight of war (war-related trauma, individual experience of violence, neglect) as well as age at trauma and the interactions of ACEs and age at trauma as predictors and three cortisol outcomes (AUC_G (area under the curve with respect to the ground), decline (morning to night) and CAR (cortisol awakening response)) was performed. For AUC_G, we found a negative association of individual experience of violence only in lACE participants. For decline, a positive association with neglect was observed for the whole study sample. The overall model for CAR was not statistically significant. Our findings support the hypothesis that type as well as timing of ACEs might influence diurnal HPA axis functioning into old age. These findings may contribute to a better understanding of the lifelong influence of ACEs.

PMID:35313255 | DOI:10.1016/j.psyneuen.2022.105717

Knee. 2022 Mar 18;35:149-156. doi: 10.1016/j.knee.2022.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Ten-segment classification provides a different approach to the evaluation of tibial plateau fractures. The purpose of this study was to assess the intra- and inter-observer reliability of three widely used classification systems (Schatzker, Arbeitsgemeinschaft für Osteosynthesefragen (AO/OTA), and the updated three-column concept (uTCC)) with ten-segment classification in two-dimensional computed tomography (2D-CT) and three-dimensional computed tomography (3D-CT).

METHOD: Ninety 2D-CT and 3D-CT scans of patients with tibial plateau fractures were included in this retrospective cohort study. The included data were independently classified by six observers of different years of seniority and were independently observed and classified again after eight weeks. Inter-observer and intra-observer reliability of the four fracture classifications made by the six observers was analyzed using the kappa statistic. Kappa values were interpreted according to the categorical rating by Landis and Koch.

RESULTS: When the inter-observer reliability was based on 2D-CT/3D-CT analysis, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.64/0.66, 0.56/0.59, 0.53/0.65, and 0.60/0.73, respectively. When intra-observer reliability was based on 2D-CT/3D-CT, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.68/0.83, 0.69/0.83, 0.74/0.85, and 0.80/0.91, respectively.

CONCLUSIONS: The use of 3D-CT is important for the reliable diagnosis and recognition of tibial plateau fracture features compared to 2D-CT. When using 3D-CT, ten-segment classification showed high intra- and inter-observer agreement.

PMID:35313243 | DOI:10.1016/j.knee.2022.03.002

Am J Emerg Med. 2022 Mar 4;55:126-132. doi: 10.1016/j.ajem.2022.02.046. Online ahead of print.

ABSTRACT

OBJECTIVE: Sodium valproate and ibuprofen are drugs with known efficacy in the treatment of headache associated with acute migraine attacks. In this study, our aim was to compare the efficacy of these two drugs in the treatment of acute migraine attacks when administered as a single intravenous (IV) dose in the emergency department.

MATERIALS AND METHOD: This study was designed as a prospective, randomized controlled, double-blinded study and included patients aged 18 to 65 years who presented to the emergency department with acute headache and met the criteria of ‘migraine without aura’ according to the International Classification of Headache Disorders. The patients were randomized into two groups and given a single dose of 800 mg sodium valproate or 800 mg ibuprofen in 150 mL of normal saline by IV infusion over five minutes. Changes in pain levels were assessed using the Numerical Rating Scale (NRS) for pain over a two-hour period.

RESULTS: Ninety-nine patients (49 patients in the sodium valproate group and 50 in the ibuprofen group) completed the trial, and their data were included in the statistical analysis. The mean decrease in the post-treatment delta NRS values was statistically significantly higher in the sodium valproate group than in the ibuprofen group. The mean differences were 1.69 [confidence interval (CI): 1.02-2.37, p<0.001], the mean difference between N0 and N2 was 3.61 (CI: 2.96-4.26, p < 0.001), the mean difference between N0 and N3 was 4.11 (CI: 3.54-4.67, p < 0.001), and the mean difference between N0 and N4 was 3.92 (CI: 3.67-4.46, p < 0.001). The number of patients who achieved the primary endpoint of pain relief was significantly higher in the sodium valproate group than in the ibuprofen group (p < 0.001). According to the Kaplan-Meier analysis showing the rates of reaching the targeted endpoint, there was a significant difference in the efficacy of the two-treatment group (χ2 = 79.98, CI: 80.35-99.65; p = 0.000).

PMID:35313227 | DOI:10.1016/j.ajem.2022.02.046

Forensic Sci Int Genet. 2022 Mar 9;58:102680. doi: 10.1016/j.fsigen.2022.102680. Online ahead of print.

ABSTRACT

The Hardy-Weinberg law is shown to be transitive in the sense that a multi-allelic polymorphism that is in equilibrium will retain its equilibrium status if any allele together with its corresponding genotypes is deleted from the population. Similarly, the transitivity principle also applies if alleles are joined, which leads to the summation of allele frequencies and their corresponding genotype frequencies. These basic polymorphism properties are intuitive, but they have apparently not been formalized or investigated. This article provides a straightforward proof of the transitivity principle, and its usefulness in genetic data analysis is explored, using high-quality autosomal microsatellite databases from the US National Institute of Standards and Technology. We address the reduction of multi-allelic polymorphisms to variants with fewer alleles, two in the limit. Equilibrium test results obtained with the original and reduced polymorphisms are generally observed to be coherent, in particular when results obtained with length-based and sequence-based microsatellites are compared. We exploit the transitivity principle in order to identify disequilibrium-related alleles, and show its usefulness for detecting population substructure and genotyping problems that relate to null alleles and allele imbalance.

PMID:35313226 | DOI:10.1016/j.fsigen.2022.102680

Stud Hist Philos Sci. 2022 Mar 18;93:39-46. doi: 10.1016/j.shpsa.2021.12.012. Online ahead of print.

ABSTRACT

Two things about Gregor Mendel are common knowledge: first, that he was the “monk in the garden” whose experiments with peas in mid-nineteenth-century Moravia became the starting point for genetics; second, that, despite that exalted status, there is something fishy, maybe even fraudulent, about the data that Mendel reported. Although the notion that Mendel’s numbers were, in statistical terms, too good to be true was well understood almost immediately after the famous “rediscovery” of his work in 1900, the problem became widely discussed and agonized over only from the 1960s, for reasons having as much to do with Cold War geopolitics as with traditional concerns about the objectivity of science. Appreciating the historical origins of the problem as we have inherited it can be a helpful step in shifting the discussion in more productive directions, scientific as well as historiographic.

PMID:35313209 | DOI:10.1016/j.shpsa.2021.12.012

Eur J Cancer. 2022 Mar 18;166:219-228. doi: 10.1016/j.ejca.2022.01.031. Online ahead of print.

ABSTRACT

AIM: The APHINITY trial showed that adding adjuvant pertuzumab (P) to trastuzumab and chemotherapy, compared with adding placebo (Pla), significantly improved invasive disease-free survival (IDFS) for patients with HER2+ early breast cancer both overall and for the node-positive (N+) cohort. We explored whether adding P could benefit some N- subpopulations and whether to consider de-escalation for some N+ subpopulations.

METHODS: Subpopulation Treatment Effect Pattern Plot (STEPP) is an exploratory, graphical method that plots estimates of treatment effect for overlapping patient subpopulations defined by a covariate of interest. We used STEPP to estimate Kaplan-Meier differences in 6-year IDFS percentages (P minus Pla: Δ ± standard error [SE]), both overall and by nodal status, for overlapping subpopulations defined by (1) a clinical composite risk score, (2) tumour infiltrating lymphocytes (TILs) percentage, and (3) human epidermal growth factor receptor 2 (HER2) FISH copy number. Because of multiplicity, a Δ of at least three SE is required to warrant attention.

RESULTS: The average absolute gains in 6-year IDFS percentages were 2.8 ± 0.9 overall; 4.5 ± 1.2 for N+ and 0.1 ± 1.1 for N-. Largest gains were for patients with intermediate clinical composite risk (5.3 ± 1.9 overall; 6.9 ± 2.3 N+; 4.0 ± 3.0 N-), highest TILs percentage (6.3 ± 1.7 overall; 7.4 ± 2.4 N+; 3.2 ± 1.7 N-), and intermediate HER2 copy number (2.8 ± 1.9 overall; 7.4 ± 2.5 N+; -1.3 ± 1.9 N-), but clear evidence indicating a pattern of differential subpopulation treatment effects was lacking.

CONCLUSIONS: STEPP plots for N- did not identify subpopulations clearly benefiting from adding P, and those for N+ did not identify subpopulations warranting de-escalation. TILs percentage appeared to be more predictive of P treatment effect than clinical composite risk score.

TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01358877.

PMID:35313167 | DOI:10.1016/j.ejca.2022.01.031

Value Health Reg Issues. 2022 Mar 18;31:1-9. doi: 10.1016/j.vhri.2022.02.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Estimation of the lost productivity cost of premature deaths because of cancers can provide invaluable information for identifying the priorities and resource needs in the design of cancer control strategies. This study aimed to estimate the premature mortality costs because of cancers using GLOBOCAN estimates in Iran.

METHODS: In this study, we estimated the lost productivity cost of premature deaths because of cancers in Iran from 2012 and 2018, using the human capital approach with respect to the cancer site, sex, and age. Data on cancer mortality were extracted from the GLOBOCAN reports. In addition, economic information, such as annual income, employment rate, housekeeping rate, and gross domestic product, was extracted from the World Bank Data and the Statistical Center of Iran. A discount rate of 3% was applied and costs were reported in constant 2017 international dollars.

RESULTS: From 2012 and 2018, the lost productivity cost of premature deaths because of cancers increased by 18% in Iran ($2453 million in 2012 and $2887 million in 2018). In contrast, the number of deaths and the years of life lost because of cancers increased by approximately 8%. The mortality cost was approximately 35% and 56% higher in men than in women in 2012 and 2018, respectively. Stomach, colorectal, esophageal, and breast cancers accounted for > 40% of total cancer mortality costs in 2012. Stomach cancer, brain cancer, nervous system cancer, lung cancer, and leukemia were responsible for 57% of cancer mortality costs in 2018.

CONCLUSIONS: Based on the findings, the lost productivity costs of premature mortality because of cancers have increased significantly in Iran. Overall, evidence-based policy making for managing the costs of cancers and resource allocation depends on analyzing epidemiological and economic data in the health sector. This study presented helpful findings on cancer mortality costs to support evidence for decision making in healthcare systems.

PMID:35313156 | DOI:10.1016/j.vhri.2022.02.002

Soc Sci Med. 2022 Feb 16;299:114828. doi: 10.1016/j.socscimed.2022.114828. Online ahead of print.

ABSTRACT

RATIONALE: Determining who is particularly vulnerable to mental health deterioration during the COVID-19 pandemic is essential when designing and targeting interventions to mitigate the adverse psychological impacts of the outbreak. Older people have appeared to be less exposed to mental health deterioration compared with younger individuals, but most exposed to the risk of severe illness and death from the virus, as well as less equipped to use technologies for coping with lockdown measures.

OBJECTIVE: Amongst the old population, we aim at determining how depressive symptoms have changed during the first wave of the COVID-19 pandemic and identifying individual risk factors associated with changes in reporting depression. We are particularly interested in exploring the role of pre-existing mental health problems and evaluating gender differences.

METHOD: Data come from the Survey of Health, Ageing and Retirement in Europe, in particular from the first COVID-19 survey administered in summer 2020. Logistic models are estimated and Average Marginal Effects computed to take the degree of individual unobserved heterogeneity into account comparing point estimates across samples. Multiple Imputation (implemented through Multivariate Imputation by Chained Equations) is used to replace missing data. Statistical power of the effect sizes is estimated by a simulation approach.

RESULTS: Pre-existing mental health problems, a diagnosis of affective/emotional disorders, a recent diagnosis of a major illness, and (only for men) job loss during the first wave of the outbreak are the most important risk factors. Statistical differences between genders emerge, with women experiencing higher levels of depression and greater worsening of mental health than men.

CONCLUSIONS: To identify people at greater risk of depression deterioration during an outbreak it is very important to consider their pre-existing mental and general health, distinguishing severity level. On population level, it is also crucial to evaluate depression disorders separately by gender.

PMID:35313142 | DOI:10.1016/j.socscimed.2022.114828

Eur J Obstet Gynecol Reprod Biol. 2022 Mar 11;272:144-149. doi: 10.1016/j.ejogrb.2022.03.021. Online ahead of print.

ABSTRACT

OBJECTIVE: Dyspareunia is a main symptom of urethral diverticulum in the female population, reported up to 60% of patients. Pain may cease after diverticulectomy as published in previous retrospective studies. To date scarce or no data exists on the postoperative outcome in terms of sexual function. The present study wants to quantify sexual function and evaluate lower urinary tract symptoms in sexually active patients after resection of urethral diverticulum.

STUDY DESIGN: In this prospective cohort trial at a tertiary referral center, we evaluated 40 female patients who presented with symptomatic urethral diverticulum and were sexually active. All of them underwent a standardized surgical procedure with inverted U-shape colpotomy between 2008 and 2018. The patients completed the Female Sexual Function Index (FSFI), which is determined by the mean score of the different domains, and underwent urodynamic assessment both at baseline examination before surgery and 12 months postoperatively. For statistical analysis, we conducted a paired Wilcoxon rank sum test analyzing the non-normally distributed non-parametric variables of the female sexual function index.

RESULTS: In two patients a malignancy was found in postoperative histology and received a different therapeutical approach. They have been excluded from statistical analysis. Sexual function improved in all domains (n = 38): total score (Z = -5.4, P < 0.000), satisfaction (Z = -5.3, P < 0.000), pain (Z = -5.4, P < 0.000), arousal (Z = -2.6, P = 0.010), lubrication (Z = -2.4, P = 0.020), desire (Z = -2.6, P = 0.009) and orgasm (Z = -2.2, P = 0.029). Maximum urethral closure pressure deteriorated from 39 to 36 cmH2O (P = 0.0008) and residual urine increased from 10 ml to 20 ml after surgery (P = 0.0019). No statistical significance is found for bladder capacity and free urinary flow.

CONCLUSIONS: All domains of the female sexual function index improved. Patients’ bothersome symptoms, mainly pain may cease and sexual satisfaction increases, which is reassuring concerning patients’ preoperative consent. We should be aware that occasionally an unexpected malignancy may be detected and it is mandatory to examine all excised tissue histologically. Lower urinary tract function remains clinically unchanged, although maximum urethral closure pressure deteriorated and postvoid residual increased though not being clinically significant.

PMID:35313135 | DOI:10.1016/j.ejogrb.2022.03.021

Ann Intern Med. 2022 Mar 22. doi: 10.7326/M21-3931. Online ahead of print.

ABSTRACT

BACKGROUND: Approximately 20.4 million Americans met criteria for a substance use disorder (SUD) in 2019; however, only about 12.2% of persons with an SUD receive specialty care. Telehealth offers alternatives to traditional forms of substance use treatment.

PURPOSE: To synthesize recent findings on the efficacy of telehealth for SUDs.

DATA SOURCES: MEDLINE, Embase, PubMed, and the Cochrane Library from January 2015 through August 2021 (English language only).

STUDY SELECTION: Randomized controlled trials (RCTs) of adults with a diagnosis of SUD based on the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases.

DATA EXTRACTION: One investigator abstracted data and assessed study quality, and a second checked for accuracy.

DATA SYNTHESIS: This rapid review synthesized evidence from 17 RCTs. Evidence is very uncertain that telehealth provided as videoconference therapy (1 RCT) or web-based cognitive behavioral therapy (CBT) (3 RCTs) has similar effects to in-person therapy for improving abstinence from alcohol or cannabis. Low-strength evidence suggests that web-based CBT has similar effects for improving abstinence in multiple SUDs (2 RCTs). Low-strength evidence suggests that adding supportive text messaging to follow-up care improves abstinence and amount of alcohol per day (2 RCTs) but does not improve emergency department visits or frequency of consumption (2 RCTs). Enhanced telephone monitoring likely reduces readmissions for SUD detoxification compared with usual follow-up alone (1 RCT) but does not reduce days of substance use (low-strength evidence).

LIMITATION: Narrative synthesis, heterogeneity of telehealth interventions, no assessment of publication bias, and study methodology.

CONCLUSION: Evidence is very uncertain that telehealth is similar to in-person care for SUD outcomes. Limited evidence suggests some benefit of adding telehealth to usual SUD care.

PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Veterans Health Administration.

PMID:35313116 | DOI:10.7326/M21-3931