Category: Statistics

Epilepsia Open. 2023 Jul 9. doi: 10.1002/epi4.12787. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the proportion of patent foramen ovale (PFO) in people with epilepsy (PWE) compared to controls without epilepsy, and to assess whether PWEs with and without PFO exhibit distinctive clinical features.

METHODS: This is a case-control study conducted in a hospital. Contrast transthoracic echocardiography with a venous microbubble bolus and provocative maneuvers (Valsalva and coughing) were used to identify PFO and its right-to-left shunt (RLS) among 741 PWEs and 800 controls without epilepsy. The risk of having PFO in PWEs was explored using multiple matching methods and logistic regression with adjusted congenital factors that may affect the occurrence of PFO.

RESULTS: The proportion of PFO in PWEs and controls were 39.00% and 24.25%, respectively. After 1:1 propensity score matching, the risk of suffering PFO in PWEs was 1.71 times (OR, 1.71; 95%CI, 1.24 – 2.36) higher than that in controls. PWEs also had a higher risk of having a high RLS grade (β_epilepsy = 0.390, p < .001). Among clinical characteristics of PWEs, migraine and drug-resistant epilepsy showed significantly different distributions between those without RLS and those with RLS grade I to III. PWEs with PFO had higher risk of suffering from migraine and drug-resistant epilepsy (OR in migraine, 2.54, 95%CI, 1.65 – 3.95; OR in drug-resistant epilepsy, 1.47, 95%CI, 1.06 – 2.03).

SIGNIFICANCE: The proportionof PFO was found to be higher in PWE than in controls without epilepsy, especially in patients with drug-resistant epilepsy, suggesting potential relationship between the two disorders. Large multicentric study will be needed to confirm this finding.

PMID:37422851 | DOI:10.1002/epi4.12787

JAMA Otolaryngol Head Neck Surg. 2023 Jul 9. doi: 10.1001/jamaoto.2023.1944. Online ahead of print.

ABSTRACT

IMPORTANCE: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear.

OBJECTIVES: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT.

DESIGN, SETTING, AND POPULATION: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform.

EXPOSURE: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy.

MAIN OUTCOMES AND MEASURES: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT.

RESULTS: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79).

CONCLUSIONS AND RELEVANCE: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

PMID:37422846 | DOI:10.1001/jamaoto.2023.1944

J Pharmacokinet Pharmacodyn. 2023 Jul 9. doi: 10.1007/s10928-023-09872-w. Online ahead of print.

ABSTRACT

Global sensitivity analysis (GSA) evaluates the impact of variability and/or uncertainty of the model parameters on given model outputs. GSA is useful for assessing the quality of Pharmacometric model inference. Indeed, model parameters can be affected by high (estimation) uncertainty due to the sparsity of data. Independence between model parameters is a common assumption of GSA methods. However, ignoring (known) correlations between parameters may alter model predictions and, then, GSA results. To address this issue, a novel two-stages GSA technique based on the δ index, which is well-defined also in presence of correlated parameters, is here proposed. In the first step, statistical dependencies are neglected to identify parameters exerting causal effects. Correlations are introduced in the second step to consider the real distribution of the model output and investigate also the ‘indirect’ effects due to the correlation structure. The proposed two-stages GSA strategy was applied, as case study, to a preclinical tumor-in-host-growth inhibition model based on the Dynamic Energy Budget theory. The aim is to evaluate the impact of the model parameter estimate uncertainty (including correlations) on key model-derived metrics: the drug threshold concentration for tumor eradication, the tumor volume doubling time and a new index evaluating the drug efficacy-toxicity trade-off. This approach allowed to rank parameters according to their impact on the output, discerning whether a parameter mainly exerts a causal or ‘indirect’ effect. Thus, it was possible to identify uncertainties that should be necessarily reduced to obtain robust predictions for the outputs of interest.

PMID:37422844 | DOI:10.1007/s10928-023-09872-w

J Manipulative Physiol Ther. 2023 Jul 6:S0161-4754(23)00027-1. doi: 10.1016/j.jmpt.2023.05.001. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the immediate effects of Mulligan’s mobilization with movement (MWM) on elbow proprioception.

METHODS: The study included 26 participants in the intervention group and 30 participants in the control group. The intervention group received MWM, while the control group received a sham application. Proprioception was assessed with joint position sense error at baseline, immediately after mobilization, and 30 minutes after mobilization with 70° and 110° of elbow flexion. The hypothesis of interest was the group × time interaction.

RESULTS: At 110° of elbow flexion, group × time interaction was significant (F[2, 108] = 11.48, P = .001). In the paired comparisons, there was a statistically significant difference in favor of the control group in the first measurement (P = .003). No difference was detected in other time points (P = 1.00). At 70° of elbow flexion, there was no significant difference between the time point × group interaction (F[2, 108] = 1.37, P = .10). Therefore, no pairwise comparison was made.

CONCLUSION: In this study of healthy participants, no immediate difference was found between MWM and sham application on elbow proprioception.

PMID:37422752 | DOI:10.1016/j.jmpt.2023.05.001

J Manipulative Physiol Ther. 2023 Jul 7:S0161-4754(23)00023-4. doi: 10.1016/j.jmpt.2023.05.005. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the effect of adding core stability to usual care for pregnant women with lumbar and pelvic girdle (LPG) pain.

METHODS: This was a repeated-measures design randomized controlled trial with blinded outcome assessors. Thirty-five pregnant women with LPG pain were recruited from prenatal health care providers. They were allocated to 2 study groups to receive either usual prenatal care (control group, n = 17) or usual care with core stability exercises focusing on the pelvic floor muscles and deep abdominal muscles (exercise group, n = 18) for 10 weeks. The visual analog scale, score on the Oswestry Disability Index, and the World Health Organization’s Quality of Life Brief Version (WHOQOL-BREF) were evaluated with analysis of variance at pre-intervention, post-intervention, at the end of pregnancy, and 6 weeks after childbirth.

RESULTS: There was a statistically significant interaction of group and time for all outcome measures except for the Social category (P = .18) in the WHOQOL-BREF questionnaire. The analysis of the group within time showed that mean scores in the exercise group were substantially improved at the post-intervention, end of pregnancy, and 6-week follow-up evaluation, except in the Environment category (end of pregnancy: P = .36; 6-week follow-up: P = .75) in the WHOQOL-BREF questionnaire.

CONCLUSION: The results of this study indicate that the addition of core stability exercises was more effective than the usual care alone in pain relief, improving disability, and quality of life of pregnant women with LPG pain.

PMID:37422748 | DOI:10.1016/j.jmpt.2023.05.005

Mayo Clin Proc. 2023 Jul 6:S0025-6196(23)00193-3. doi: 10.1016/j.mayocp.2023.03.024. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association of early-life tobacco smoke exposure, especially interacting with cancer genetic variants, with adult cancer.

PARTICIPANTS AND METHODS: We examined the associations of in utero tobacco smoke exposure, age of smoking initiation, and their interaction with genetic risk levels with cancer incidence in 393,081 participants from the UK Biobank. Information on tobacco exposure was obtained by self-reported questionnaires. A cancer polygenic risk score was constructed by weighting and integrating 702 genome-wide association studies-identified risk variants. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for overall cancer and organ-specific cancer incidence.

RESULTS: During 11.8 years of follow-up, 23,450 (5.97%) and 23,413 (6.03%) incident cancers were included in the analyses of in utero exposure and age of smoking initiation, respectively. The HR (95% CI) for incident cancer in participants with in utero exposure to tobacco smoke was 1.04 (1.01-1.07) for overall cancer, 1.59 (1.44-1.75) for respiratory cancer, and 1.09 (1.03-1.17) for gastrointestinal cancer. The relative risk of incident cancer increased with earlier smoking initiation (P_trend<.001), with the HR (95% CI) of 1.44 (1.36-1.51) for overall cancer, 13.28 (11.39-15.48) for respiratory cancer, and 1.72 (1.54-1.91) for gastrointestinal cancer in smokers with initiation in childhood compared with never smokers. Importantly, a positive additive interaction between age of smoking initiation and genetic risk was observed for overall cancer (P_additive=.04) and respiratory cancer (P_additive=.003) incidence.

CONCLUSION: In utero exposure and earlier smoking initiation are associated with overall and organ-specific cancer, and age of smoking initiation interaction with genetic risk is associated with respiratory cancer.

PMID:37422733 | DOI:10.1016/j.mayocp.2023.03.024

Sleep. 2023 Jul 9:zsad177. doi: 10.1093/sleep/zsad177. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Sleep-related adverse effects during acute treatment with antidepressants undermine compliance and impede remission. We aimed to address subtypes of sleep-related adverse effects and depict the relationship between dose and sleep-related adverse events.

METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for double-blind randomized controlled trials of depression published before April 30th, 2023. Eligible studies reporting sleep-related adverse effects during short-term monotherapy were included. The odds ratios (ORs) for sleep-related adverse effects were addressed with network meta-analysis. A Bayesian approach was used to depict the dose-effect relationship. Heterogeneity among studies was assessed using the τ 2 and I 2 statistics. Sensitivity analyses were performed without studies featured high risk of bias.

RESULTS: Studies with 64,696 patients were examined from 216 trials. Comparing to placebo, 13 antidepressants showed higher ORs for somnolence, of which fluvoxamine (OR=6.32; 95%CI: 3.56-11.21) ranked the top. Eleven had higher risks for insomnia, reboxetine ranked the top (OR=3.47; 95%CI: 2.77-4.36). The dose-effect relationships curves between somnolence or insomnia and dose included linear shape, inverted U-shape and other shapes. There was no significant heterogeneity among individual studies. The quality of evidence for results in network meta-analyses was rated as very low to moderate by GRADE.

CONCLUSIONS: Most antidepressants had higher risks for insomnia or somnolence than placebo. The diverse relationship curves between somnolence or insomnia and dose of antidepressants can guide clinicians to adjust the doses. These findings suggest clinician pay more attention to sleep-related adverse effects during acute treatment with antidepressants.

PMID:37422714 | DOI:10.1093/sleep/zsad177

J Comput Assist Tomogr. 2023 Jul 7. doi: 10.1097/RCT.0000000000001511. Online ahead of print.

ABSTRACT

OBJECTIVE: In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition.

METHODS: This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050.

RESULTS: A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) (P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) (P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) (P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) (P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant.

CONCLUSIONS: The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation.

PMID:37422693 | DOI:10.1097/RCT.0000000000001511

Clin Pharmacol Ther. 2023 Jul 8. doi: 10.1002/cpt.2982. Online ahead of print.

ABSTRACT

Oral azacitidine (Oral-AZA) maintenance is approved for adults with acute myeloid leukemia (AML) in remission post-intensive chemotherapy, not proceeding to hematopoietic stem cell transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model to characterize Oral-AZA concentration-time profiles in patients with AML, myelodysplastic syndrome, or chronic myelomonocytic leukemia. PopPK-estimated exposure parameters were used to evaluate exposure-response relationships in the phase 3 QUAZAR AML-001 study. The PopPK dataset comprised 286 patients with 1933 evaluable Oral-AZA concentration records. The final PopPK model was a one-compartment model with first-order absorption incorporating an absorption lag time and first-order elimination. Regression analyses identified two Oral-AZA exposure parameters (area under the plasma concentration-time curve at steady state [AUC_ss ]; maximum plasma concentration [C_max ]) as statistically significant predictors for relapse-free survival (HR=0.521, p<0.001; HR=0.630, p=0.013; respectively), and AUC_ss as a significant predictor for overall survival (HR=0.673, p=0.042). The probability of Grade ≥3 neutropenia was significantly increased with increases in AUC_ss (OR=5.71, 95% CI=2.73-12.62, p<0.001), cumulative AUC through cycles 1 to 6 (OR=2.71, 95% CI=1.76-4.44, p<0.001), and C_max at steady state (OR=2.38, 95% CI=1.23-4.76, p=0.012). A decreasing trend was identified between AUC_ss and relapse-related schedule extensions, versus an increasing trend between AUC_ss and event-related dose reductions. As the majority (56.8%) of patients required no dose modifications, and the proportions requiring schedule extension (19.4%) or dose reduction (22.9%) were almost equal, Oral-AZA 300 mg once daily for 14 days is the optimal dosing schedule balancing survival benefit and safety risk.

PMID:37422689 | DOI:10.1002/cpt.2982

Ital J Pediatr. 2023 Jul 8;49(1):80. doi: 10.1186/s13052-023-01491-y.

ABSTRACT

BACKGROUND: To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP).

METHODS: Eighty-two RMPP patients admitted to Pediatrics at The First People’s Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups.

RESULTS: The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05).

CONCLUSIONS: BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.

PMID:37422684 | DOI:10.1186/s13052-023-01491-y