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Comparison of various methods for validity evaluation of QSAR models

BMC Chem. 2022 Aug 23;16(1):63. doi: 10.1186/s13065-022-00856-4.

ABSTRACT

BACKGROUND: Quantitative structure-activity relationship (QSAR) modeling is one of the most important computational tools employed in drug discovery and development. The external validation of QSAR models is the main point to check the reliability of developed models for the prediction activity of not yet synthesized compounds. It was performed by different criteria in the literature.

METHODS: In this study, 44 reported QSAR models for biologically active compounds reported in scientific papers were collected. Various statistical parameters of external validation of a QSAR model were calculated, and the results were discussed.

RESULTS: The findings revealed that employing the coefficient of determination (r2) alone could not indicate the validity of a QSAR model. The established criteria for external validation have some advantages and disadvantages which should be considered in QSAR studies.

CONCLUSION: This study showed that these methods alone are not only enough to indicate the validity/invalidity of a QSAR model.

PMID:35999611 | DOI:10.1186/s13065-022-00856-4

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Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis

Thromb J. 2022 Aug 23;20(1):47. doi: 10.1186/s12959-022-00408-9.

ABSTRACT

BACKGROUND: Previous studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial.

METHODS: We systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity.

RESULTS: We identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78-1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98-1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19-2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56-3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39-0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66-1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39-0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34-1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results.

CONCLUSIONS: In our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs.

TRIAL REGISTRATION: Protocol registration: The protocol was registered at PROSPERO (CRD42021293294).

PMID:35999599 | DOI:10.1186/s12959-022-00408-9

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Towards school-based mental health programs in Nigeria: the immediate impact of a depression-literacy program among school-going adolescents and their teachers

Child Adolesc Psychiatry Ment Health. 2022 Aug 23;16(1):70. doi: 10.1186/s13034-022-00503-9.

ABSTRACT

BACKGROUND: Depression-literacy, which is the foundational requirement for symptom recognition, positive attitude and help-seeking, is poor among adolescents in Nigeria. This study, therefore, aims to determine the impact of a school-based training program on depression-literacy among a cohort of high-school students and their teachers in South-West Nigeria.

METHODS: An adapted version of the Break Free from Depression, a 4-module depression awareness curriculum for staff and students, was implemented among students and their teachers. Paired-sample T-test was used to assess the domain-specific (knowledge, attitude, and confidence) impact of the training by comparing the baseline and immediate (within the week of the training) post-scores.

RESULTS: A total of 3098 students and 294 teachers from 21 schools across three states in South-West Nigeria successfully completed the training. There was a significant positive difference (p < 0.05), at post-test, in the knowledge, attitude, and confidence among the students. The same was observed among teachers except for attitude where positive change did not reach significant level (p = 0.06). When statistically significant, the calculated effect size (eta squared) was highest for knowledge (students: 0.07, p = 0.001; teachers: 0.08, p < 0.000) and least for attitude (students: 0.003, p = 0.002 teachers: 0.085, p = 0.06). Multiple regression analyses result showed that the level of pre-scores predicted the magnitude of change in all domains of depression-literacy (p < 0.05) after controlling for age, gender, and type of school among the students, but not for teachers.

CONCLUSIONS: School-based depression-literacy programs can lead to significant positive change in knowledge, attitude, and confidence of students and teachers.

PMID:35999596 | DOI:10.1186/s13034-022-00503-9

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Cannabidiol as a treatment for arthritis and joint pain: an exploratory cross-sectional study

J Cannabis Res. 2022 Aug 24;4(1):47. doi: 10.1186/s42238-022-00154-9.

ABSTRACT

INTRODUCTION: An estimated 54 million Americans currently suffer from debilitating arthritis. Patients who have exhausted conservative measures can be subject to chronic pain and resort to symptomatic management with anti-inflammatories, acetaminophen, and opioids. Cannabidiol (CBD) is a non-psychoactive cannabinoid that has shown promise in preclinical studies to reduce inflammation and pain associated with arthritis. The purpose of this study was to explore patient perceived effects of cannabidiol on symptoms of arthritis.

METHODS: A novel anonymous questionnaire was created to evaluate perceived efficacy of cannabidiol for the treatment of arthritis. A self-selected convenience sample (N=428) was recruited through online methods including social media accounts and newsletters (The Arthritis Foundation and Savvy Cooperative) between May 5, 2020, and November 5, 2020. Statistical analysis was performed to determine differences between types of arthritis and improvements in quality-of-life symptoms. Furthermore, a regression analysis was performed to identify variables associated with decreasing or discontinuing other medications.

RESULTS: CBD use was associated with improvements in pain (83%), physical function (66%), and sleep quality (66%). Subgroup analysis by diagnosis type (osteoarthritis, rheumatoid, or other autoimmune arthritis) found improvements among groups for physical function (P=0.013), favoring the osteoarthritis group. The overall cohort reported a 44% reduction in pain after CBD use (P<0.001). The osteoarthritis group had a greater percentage reduction (P=0.020) and point reduction (P<0.001) in pain compared to rheumatoid arthritis and other autoimmune arthritis. The majority of respondents reported a reduction or cessation of other medications after CBD use (N=259, 60.5%): reductions in anti-inflammatories (N=129, 31.1%), acetaminophen (N=78, 18.2%), opioids (N=36, 8.6%) and discontinuation of anti-inflammatories (N=76, 17.8%), acetaminophen (N=76, 17.8%), and opioids (N=81, 18.9%).

CONCLUSION: Clinicians and patients should be aware of the various alternative therapeutic options available to treat their symptoms of arthritis, especially in light of the increased accessibility to cannabidiol products. The present study found associations between CBD use and improvements in patient’s arthritis symptoms and reductions in other medications. Future research should focus on exploring the benefits of CBD use in this patient population with clinical trials.

PMID:35999581 | DOI:10.1186/s42238-022-00154-9

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Reassessment of intensive surveillance practices adopted for endometrial cancer survivors

BMC Womens Health. 2022 Aug 23;22(1):355. doi: 10.1186/s12905-022-01937-1.

ABSTRACT

BACKGROUND: In Japan, 17,000 women are newly diagnosed with endometrial cancer in 2018. The healthcare insurance policy in Japan provides more intensive patient surveillance compared with the United States and European countries. The aim of this study was to retrospectively analyze data, including surveillance methods, recurrence sites, salvage therapy, and survival period after recurrence, to consider the benefits of surveillance for patients with endometrial cancer.

METHODS: Between January 2009 and December 2015, the medical records of patients who were initially diagnosed with the International Federation of Gynecology and Obstetrics stage I-IV endometrial cancer and treated were enrolled in this retrospective study. Only patients with stage IV cancer with peritoneal dissemination were included. Within the first 2 years, the included patients underwent tumor marker tests, Papanicolaou smear test every 1-3-months, and imaging analysis at 6-12- month intervals. Until 4 years, the patients underwent regular surveys every 4 months and imaging analysis annually. Subsequently, the patients received regular surveys every 6 -to 12-months.

RESULTS: Among 847 patients, 88 experienced recurrence, and their clinicopathological data were statistically analyzed. The recurrence site was not associated with the initial treatment method or histology. Among the patients with recurrence, 75% were asymptomatic. Univariate analysis demonstrated that time to recurrence and local recurrence were significant factors for survival outcomes, whereas multivariate analysis indicated that only local recurrence was a significant factor. In patients with distant metastasis, neither symptomatic nor asymptomatic recurrence showed a significant difference in survival.

CONCLUSIONS: In this retrospective study, an intensive surveillance protocol did not benefit patients with endometrial cancer. Thus, we hypothesize that the characterization of tumors by emerging technologies that can precisely predict the nature of the tumor will help tailor individualized and efficient surveillance programs. In addition, the ideal salvage therapy needs to be developed to benefit patients after recurrence.

PMID:35999573 | DOI:10.1186/s12905-022-01937-1

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Genetic predispositions to psychiatric disorders and the risk of COVID-19

BMC Med. 2022 Aug 23;20(1):314. doi: 10.1186/s12916-022-02520-z.

ABSTRACT

BACKGROUND: Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown.

METHODS: Our analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population (“base dataset”). For the other half (“target dataset”), the polygenic risk score (PRS) was calculated as a proxy of individuals’ genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered “severe cases.” The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics.

RESULTS: A total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02-1.13) and 1.06 (95% CI 1.01-1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics.

CONCLUSIONS: Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.

PMID:35999565 | DOI:10.1186/s12916-022-02520-z

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The effect of berberine and fenugreek seed co-supplementation on inflammatory factor, lipid and glycemic profile in patients with type 2 diabetes mellitus: a double-blind controlled randomized clinical trial

Diabetol Metab Syndr. 2022 Aug 23;14(1):120. doi: 10.1186/s13098-022-00888-9.

ABSTRACT

BACKGROUND: Type 2 Diabetes mellitus is one of the most common chronic diseases in the world and has many complications. Due to the importance of using alternative therapies in managing symptoms of this disease, the present study was designed and conducted to investigate the effect of co-supplementation of berberine and fenugreek in patients with type 2 diabetes mellitus.

METHODS: A randomized controlled clinical trial was conducted on 50 patients with type 2 diabetes mellitus. Participants were randomized in the intervention group, which received 3 capsules/day of 500 mg (300 mg of berberine + 200 mg of fenugreek seed powder) or placebo for 12 weeks. Biochemical and anthropometric variables were measured at the beginning and end of the study.

RESULTS: We observed that fasting insulin, HbA1C, and hs-CRP significantly decreased in the intervention group compared to the baseline. The mean difference in insulin resistance (-0.32 vs. 0.15), fasting blood sugar (-14.40 vs. 1.68), and fasting insulin (- 2.18 vs. 1.34) were clinically significant in comparison to the control group. Almost all domains of SF-12 scores were significantly higher in the intervention group than in the placebo group.

CONCLUSIONS: The combination of berberine and fenugreek seed can improve cardio-metabolic status in patients with diabetes and support the anti-diabetic and anti-inflammatory role of herb in the improvement of quality of life.

PMID:35999562 | DOI:10.1186/s13098-022-00888-9

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Development of a “Scissor-Tip-Separator” for adjustment of scissor blade separation and prevention of scissor blade damage during steam sterilization

Patient Saf Surg. 2022 Aug 23;16(1):28. doi: 10.1186/s13037-022-00338-5.

ABSTRACT

BACKGROUND: Reprocess reusable surgical instruments during steam sterilization; damage occurs to sharp scissor blades in close position, so steam cannot reach the blades. Surgical instruments’ management requires standards to ensure patient safety and prevent harmful pathogens, especially in the COVID-19 pandemic. Although various devices can separate scissor blades, they do not prevent damage to cutting edges. To address the above problem, we developed a new scissor protector, the “Scissor-Tip-Separator,” and evaluated its efficacy.

METHODS: The “Scissor-Tip-Separator” design follows the steam sterilization guideline that instrument tips must be separated. The locking handles and V groove mechanism keep the scissor blades separated while preventing damage to the cutting edges. For efficacy assessment, purposive sampling was performed to select 44 Thai perioperative nurses at Ramathibodi Hospital, Bangkok, Thailand, to evaluate the “Scissor-Tip-Separators” in 450 sterile instrument containers. All participants evaluated surgical scissors placed in the “Scissor-Tip-Separators” during instrument setup, following a problem record checklist. At the end of the fifth use, participants were asked to complete the “Scissor-Tip-Separator” Effectiveness Scale, which was used to test the structural design of the “Scissor-Tip-Separator” in terms of function, usability, and safety. The Adenosine Triphosphate surface test was also used to validate the “Scissor-Tip-Separator” cleanliness. Data were collected from August 2020 to November 2020, then analyzed via descriptive statistics.

RESULTS: The “Scissor-Tip-Separator” met the cleaning validation criteria, and in 44 uses, the physical property remained the same. The scissor shank was discovered loose from the handle before it had been unlocked (0.2-0.4%) at the 45th use. Based on participants’ opinions, the overall instrument effectiveness was high in terms of function, usability, and safety.

CONCLUSION: The “Scissor-Tip-Separator” regulates scissor blade separation under sterilization guidelines; it prevents damage to cutting edges, thus ensuring patient safety. It protects against losses in a sterile field and can prevent hand injuries.

PMID:35999555 | DOI:10.1186/s13037-022-00338-5

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Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes

Cardiovasc Diabetol. 2022 Aug 23;21(1):161. doi: 10.1186/s12933-022-01599-1.

ABSTRACT

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM.

METHODS: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients’ (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed.

RESULTS: Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value.

CONCLUSIONS: In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www.

CLINICALTRIALS: gov . Unique identifier: NCT00000620.

PMID:35999546 | DOI:10.1186/s12933-022-01599-1

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Mobile phone addiction and depression among Chinese medical students: the mediating role of sleep quality and the moderating role of peer relationships

BMC Psychiatry. 2022 Aug 23;22(1):567. doi: 10.1186/s12888-022-04183-9.

ABSTRACT

The literature has shown that mobile phone addiction is an important risk factor for depression. However, the internal mechanisms of mobile phone addiction leading to depression are still not clear. This study examined the mediating role of sleep quality and moderating role of peer relationships in the association between mobile phone addiction and depression. A sample of 450 Chinese medical students were recruited to complete measures of mobile phone addiction, depression, sleep quality and peer relationships. In this study, SPSS 25.0 and macro PROCESS were used to conduct statistical analysis on the collected data. The results showed that sleep quality partially mediated the association between mobile phone addiction and depression. Moreover, the effect of sleep quality on depression was moderated by peer relationships. The present study can advance our understanding of how and when mobile phone addiction leads to depression. Limitations and implications of this study are discussed.

PMID:35999533 | DOI:10.1186/s12888-022-04183-9