Tag: pubmed

JAMA Psychiatry. 2021 Sep 22. doi: 10.1001/jamapsychiatry.2021.2500. Online ahead of print.

ABSTRACT

IMPORTANCE: Clinical trials have identified numerous prescriptive predictors of mental disorder treatment response, ie, predictors of which treatments are best for which patients. However, none of these prescriptive predictors is strong enough alone to guide precision treatment planning. This has prompted growing interest in developing precision treatment rules (PTRs) that combine information across multiple prescriptive predictors, but this work has been much less successful in psychiatry than some other areas of medicine. Study designs and analysis schemes used in research on PTR development in other areas of medicine are reviewed, key challenges for implementing similar studies of mental disorders are highlighted, and recent methodological advances to address these challenges are described here.

OBSERVATIONS: Discovering prescriptive predictors requires large samples. Three approaches have been used in other areas of medicine to do this: conduct very large randomized clinical trials, pool individual-level results across multiple smaller randomized clinical trials, and develop preliminary PTRs in large observational treatment samples that are then tested in smaller randomized clinical trials. The third approach is most feasible for research on mental disorders. This approach requires working with large real-world observational electronic health record databases; carefully selecting samples to emulate trials; extracting information about prescriptive predictors from electronic health records along with other inexpensive data augmentation strategies; estimating preliminary PTRs in the observational data using appropriate methods; implementing pragmatic trials to validate the preliminary PTRs; and iterating between subsequent observational studies and quality improvement pragmatic trials to refine and expand the PTRs. New statistical methods exist to address the methodological challenges of implementing this approach.

CONCLUSIONS AND RELEVANCE: Advances in pragmatic precision psychiatry will require moving beyond the current focus on randomized clinical trials and adopting an iterative discovery-confirmation process that integrates observational and experimental studies in real-world clinical populations.

PMID:34550327 | DOI:10.1001/jamapsychiatry.2021.2500

Am J Epidemiol. 2021 Sep 22:kwab235. doi: 10.1093/aje/kwab235. Online ahead of print.

ABSTRACT

In clinical and epidemiological studies, hazard ratios are often applied to compare treatment effects between two groups for survival data. For competing risks data, the corresponding quantities of interest are cause-specific hazard ratios (cHRs) and subdistribution hazard ratios (sHRs). However, they both have some limitations related to model assumptions and clinical interpretation. Therefore, we recommend restricted mean time lost (RMTL) as an alternative that is easy to interpret in a competing risks framework. Based on the difference in restricted mean time lost (RMTLd), we propose a new estimator, hypothetical test and sample size formula. The simulation results show that the estimation of the RMTLd is accurate and that the RMTLd test has robust statistical performance (both type I error and power). The results of three example analyses also verify the performance of the RMTLd test. From the perspectives of clinical interpretation, application conditions and statistical performance, we recommend that the RMTLd be reported with the HR in the analysis of competing risks data and that the RMTLd even be regarded as the primary outcome when the proportional hazard assumption fails.

PMID:34550319 | DOI:10.1093/aje/kwab235

JAMA Psychiatry. 2021 Sep 22. doi: 10.1001/jamapsychiatry.2021.2588. Online ahead of print.

ABSTRACT

IMPORTANCE: Mortality associated with methamphetamine use has increased markedly in the US. Understanding patterns of methamphetamine use may help inform related prevention and treatment.

OBJECTIVE: To assess the national trends in and correlates of past-year methamphetamine use, methamphetamine use disorder (MUD), injection, frequent use, and associated overdose mortality from 2015 to 2019.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed methamphetamine use, MUD, injection, and frequent use data from participants in the 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). Mortality data were obtained from the 2015 to 2019 National Vital Statistics System Multiple Cause of Death files.

EXPOSURES: Methamphetamine use.

MAIN OUTCOMES AND MEASURES: Methamphetamine use, MUD, injection, frequent use, and overdose deaths.

RESULTS: Of 195 711 NSDUH respondents aged 18 to 64 years, 104 408 were women (weighted percentage, 50.9%), 35 686 were Hispanic individuals (weighted percentage, 18.0%), 25 389 were non-Hispanic Black (hereafter, Black) individuals (weighted percentage, 12.6%), and 114 248 were non-Hispanic White (hereafter, White) individuals (weighted percentage, 60.6%). From 2015 to 2019, overdose deaths involving psychostimulants other than cocaine (largely methamphetamine) increased 180% (from 5526 to 15 489; P for trend <.001); methamphetamine use increased 43% (from 1.4 million [95% CI, 1.2-1.6 million] to 2.0 million [95% CI, 1.7-2.3 million]; P for trend = .002); frequent methamphetamine use increased 66% (from 615 000 [95% CI, 512 000-717 000] to 1 021 000 [95% CI, 860 000-1 183 000]; P for trend = .002); methamphetamine and cocaine use increased 60% (from 402 000 [95% CI, 306 000-499 000] to 645 000 [95% CI, 477 000-813 000]; P for trend = .001); and MUD without injection increased 105% (from 397 000 [95% CI, 299 000-496 000] to 815 000 [95% CI, 598 000-1 033 000]; P for trend = .006). The prevalence of MUD or injection surpassed the prevalence of methamphetamine use without MUD or injection in each year from 2017 to 2019 (60% to 67% vs 37% to 40%; P for trend ≤.001). Adults with MUD or using injection were more likely to use methamphetamine frequently (52.68%-53.84% vs 32.59%; adjusted risk ratio, 1.62-1.65; 95% CI, 1.35-1.94). From 2015 to 2019, the adjusted prevalence of MUD without injection more than tripled among heterosexual women (from 0.24% to 0.74%; P < .001) and lesbian or bisexual women (from 0.21% to 0.71%; P < .001) and more than doubled among heterosexual men (from 0.29% to 0.79%; P < .001) and homosexual or bisexual men (from 0.29% to 0.80%; P = .007). It increased over 10-fold among Black individuals (from 0.06% to 0.64%; P < .001), nearly tripled among White individuals (from 0.28% to 0.78%; P < .001), and more than doubled among Hispanic individuals (from 0.39% to 0.82%; P < .001). Risk factors for methamphetamine use, MUD, injection, and frequent use included lower educational attainment, lower annual household income, lack of insurance, housing instability, criminal justice involvement, comorbidities (eg, HIV/AIDS, hepatitis B or C virus, depression), suicidal ideation, and polysubstance use.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found consistent upward trends in overdose mortality, greater risk patterns of methamphetamine use, and populations at higher risk for MUD diversifying rapidly, particularly those with socioeconomic risk factors and comorbidities. Evidence-based prevention and treatment interventions are needed to address surges in methamphetamine use and MUD.

PMID:34550301 | DOI:10.1001/jamapsychiatry.2021.2588

Braz J Biol. 2021 Sep 20;83:e248910. doi: 10.1590/1519-6984.248910. eCollection 2021.

ABSTRACT

This study determines the associations among serum lipid profiles, risk of cardiovascular disease, and persistent organic pollutants. Using Gas chromatography technique, the intensity of toxic pollutant residues in serum samples of Hypertensive patients were measured. Based on statistical analysis, the effects of different covariates namely pesticides, age, systolic blood pressure, diastolic blood pressure, and lipid profile duration was checked using the logistic regression model. Statistical computation was performed on SPSS 22.0. The P-values of F-Statistic for each lipid profile class are greater than 0.01 (1%), therefore we cannot reject the null hypothesis for all cases. The estimated coefficients, their standard errors, Wald Statistic, and odds ratio of the binary logistic regression model for different lipid profile parameters indicate if pesticides increase then the logit value of different lipid profile parameters changes from -0.46 to -0.246 except LDL which increases by 0.135. The study reports a significantly increased threat of cardiovascular disease with increased concentrations of toxic pollutants.

PMID:34550288 | DOI:10.1590/1519-6984.248910

Braz J Biol. 2021 Sep 20;83:e251198. doi: 10.1590/1519-6984.251198. eCollection 2021.

ABSTRACT

The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.

PMID:34550296 | DOI:10.1590/1519-6984.251198

Rev Assoc Med Bras (1992). 2021 Jun;67(5):736-740. doi: 10.1590/1806-9282.20210139.

ABSTRACT

OBJECTIVE: Decompressive craniectomy may be a life-saving measure in ischemic stroke patients, who still have several associated complications. The objective of this study is to evaluate a novel decompressive surgery technique for severe hemispheric ischemic stroke.

METHODS: For the hinge decompressive craniectomy (HDC), linear durotomies were performed. Vertical (one or two frontal and two parietal), and two horizontal (temporal), with approximately 5 cm long, linear durotomies were carried out. Duroplasty was performed using an autologous subgaleal tissue graft fixed with separate sutures to avoid CSF leak and direct contact of the cortex with the bone flap. The bone flap was fixed in three parietal locations. We compared 10 patients who underwent our modified HDC with 9 patients submitted to classical decompressive craniectomy (CDC). The primary outcome of this study was mortality.

RESULTS: Nineteen patients were included, with a mean age of 52.3 years (±8.2). Four (44%) patients from the HDC group had to be reoperated to remove the bone flap because of brain swelling worsening, but none of them died. The average time of HDC was 90 minutes. Overall 14-days mortality was 21.1% (n=4), and cumulative six-months mortality was 42.1% (n=8). Five (50%) patients submitted to CDC died, while 3 (33.3%) submitted to HDC died (χ2=0.07, p=0.79). The mean length of stay was 46.7 days (±32.1) for HDC and 38.7 (±27.1) for CDC (p=0.60).

CONCLUSIONS: We present a modified technique of hinge craniectomy with linear vertical and horizontal durotomies, which seems to have reduced operative time and mortality compared to classical decompressive craniotomy, although the difference was not statistically significant.

PMID:34550265 | DOI:10.1590/1806-9282.20210139

Rev Bras Ter Intensiva. 2021 Sep 20:S0103-507X2021005001201. doi: 10.5935/0103-507X.20210050. Online ahead of print.

ABSTRACT

OBJECTIVE: To understand the perception of patients about medical communication as well as their needs during hospitalization in the intensive care unit.

METHODS: This study was cross-sectional descriptive and qualitative exploratory including 103 patients admitted to or recently discharged from the intensive care units of four hospitals in Greater Florianópolis, Santa Catarina state, Brazil. The patients’ sociodemographic and clinical variables were studied, as were the score they gave to the quality of medical communication through the Quality of Communication Questionnaire and their spontaneous comments with reflections or justifications for the scores given, and their responses on how they felt and what complementary help they would have liked to receive. The quantitative data were analyzed by descriptive and analytical statistics, and the qualitative data were analyzed by thematic content analysis.

RESULTS: The mean Quality of Communication Questionnaire score was 5.1 (standard deviation – SD = 1.3), with 8.6 (SD = 1.3) on the general communication subscale and 2.1 (SD = 1.8) on the end-of-life communication subscale. The patients had a variable understanding of medical language. Some physicians seemed to be “rushed”, according to some patients. Other patients would like to receive more frequent and detailed information and/or be respected and taken “more seriously” when they reported pain. Anxiety, sadness, and fear were among the reported feelings. Other needs included silence, more time for visits, the presence of a companion, psychological and social-work care, a bathroom that they could use, and better food in the intensive care unit.

CONCLUSION: The quality of medical communication with patients is good but could improve if physicians and the healthcare team had more time for patients. Other felt needs included respect, pain relief, and adjustments in the intensive care unit dynamics and environment.

PMID:34550276 | DOI:10.5935/0103-507X.20210050

Rev Assoc Med Bras (1992). 2021 Jun;67(5):650-655. doi: 10.1590/1806-9282.20200737.

ABSTRACT

OBJECTIVE: To assess the impact of the metoclopramide-induced hyperprolactinemia in cellular death and proliferation in the harderian gland of female mice.

METHODS: Twenty female mice were divided into two groups of 10 animals each and treated: 0.2 mL of saline solution (controls, Ctr) and 200 µg of metoclopramide (experimental, hyperprolactinemia), both for 50 consecutive days and at 12:00 a.m. On the 50th day, the female were euthanized, and the harderian glands were removed and processed for immunohistochemistry for detected ki67 and TUNEL method. Data were statistically analyzed by unpaired Student’s t test (p<0.05).

RESULTS: The harderian gland of the hyperprolactinemia group showed increase in the immunoexpression of Ki67 and TUNEL compared to the Ctr group (p<0.05), and there was no significant difference in the amount of porphyrin in the HPrl group compared to the Ctr group.

CONCLUSION: The hyperprolactinemia led to increased cell death in the acini the harderian gland and cell proliferation in the stroma glandular, fact that suggesting a reduction process of cellular activity and fibrosis, which suggests impairment in the functioning of the lacrimal harderian.

PMID:34550251 | DOI:10.1590/1806-9282.20200737

Rev Assoc Med Bras (1992). 2021 Jun;67(5):713-717. doi: 10.1590/1806-9282.20201166.

ABSTRACT

OBJECTIVE: Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of incontinence. The aim of this study is to evaluate the effect of mirabegron and duloxetine combination in the treatment of mixed-type urinary incontinence.

METHODS: The data of 88 mixed-type urinary incontinence patients who applied to the urology outpatient clinic between January 2018 and December 2019 were retrospectively analyzed. We applied mirabegron and duloxetine treatment to the patients. The International Consultation of Incontinence Questionnaire-Short Form, Overactive bladder symptom score questionnaire and daily pad count were statistically evaluated before and after the treatment.

RESULTS: Statistically significant improvements were observed using the questionnaire forms and decreased daily pad usage after the eight-week treatment (p<0.001). Based on the clinical global effect scale, 62.50% of patients had a partial or complete response to treatment and also the use of daily pads were decreased from 3.7-0.89 on an average.

CONCLUSION: Combination use of mirabegron and duloxetine in the treatment of mixed-type urinary incontinence improved symptom scores and decreased pad usage.

PMID:34550261 | DOI:10.1590/1806-9282.20201166

Arq Bras Cardiol. 2021 Sep;117(3):476-483. doi: 10.36660/abc.20190902.

ABSTRACT

BACKGROUND: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known.

OBJECTIVES: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes.

METHODS: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant.

RESULTS: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels.

CONCLUSIONS: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.

PMID:34550233 | DOI:10.36660/abc.20190902