Category: Statistics

J Pharmacokinet Pharmacodyn. 2022 Feb 13. doi: 10.1007/s10928-022-09808-w. Online ahead of print.

ABSTRACT

Nonadherence to medication is a major public health problem. To combat nonadherence, some clinicians have suggested using “forgiving” drugs, which maintain efficacy in spite of delayed or missed doses. What pharmacokinetic (PK) and pharmacodynamic (PD) factors make a drug forgiving? In this paper, we address this question by analyzing a linear PK/PD model for a patient with imperfect adherence. We assume that the drug effect is far from maximal and consider direct effect, effect compartment (biophase), and indirect response PD models. We prove that the average drug effect relative to the clinically desired effect is simply the fraction of prescribed doses actually taken by the patient. Hence, under these assumptions, drug forgiveness cannot be defined in terms of the average effect. We argue that forgiveness should instead be understood in terms of effect fluctuations. We prove that the rates of PK absorption, PK elimination, and PD elimination are exactly equivalent for determining effect fluctuations. We prove all the aforementioned results for any pattern of nonadherence, including late doses, missed doses, drug holidays, extra doses, etc. To obtain quantitative estimates of effect fluctuations, we consider a simple statistical pattern of nonadherence and analytically calculate the coefficient of variation of effect. We further show how effect fluctuations can be reduced by taking an extra “make up” dose following a missed dose if any one of the aforementioned PK/PD rates is sufficiently slow. We illustrate some of our results for a nonlinear indirect response model of metformin.

PMID:35156179 | DOI:10.1007/s10928-022-09808-w

Curr Rev Musculoskelet Med. 2022 Feb 14. doi: 10.1007/s12178-022-09747-6. Online ahead of print.

ABSTRACT

PURPOSE OF THE REVIEW: Consensus on the effects of soft tissue surgical intervention in the management of brachial plexus birth injury (BPBI) sequalae is lacking. The purpose of this review is to examine the available literature on the functional and structural outcomes following soft tissue surgical management of BPBI sequalae.

RECENT FINDINGS: EMBASE, PubMed, and MEDLINE were searched for related literature from the point of database inception until April 2021. Relevant papers were screened by two reviewers independently and in duplicate. A meta-analysis was performed using a random effects model. A total of 25 studies (852 patients) were included in the review, with the number included in each meta-analysis varying based on outcome of interest. There were significant improvements from pre- to post-operative time points for the following measures: Mallet aggregate scores (5.0 points, p<0.0001), active external rotation in adduction (48.9°, p=0.003), passive external rotation in adduction (64.6°, p< 0.00001), active abduction (46.2°, p<0.00001), glenoid version (14.4°, p< 0.00001), and percentage of the humeral head anterior to the scapular line (17.53°, p< 0.00001). Furthermore, data revealed an overall complication rate of 9.3% (79/852 patients) and a major complication rate of 0.47% (4/852 patients). Patients with BPBI sequela experience statistically significant improvements in functional, structural, and range of motion outcomes of the GH joint following soft tissue surgical management. Understanding the ideal indications for each procedure and age of surgical management with future prospective studies will help to optimize surgical management of these patients.

PMID:35156170 | DOI:10.1007/s12178-022-09747-6

Environ Monit Assess. 2022 Feb 14;194(3):178. doi: 10.1007/s10661-022-09811-1.

ABSTRACT

This study aimed to transform the input of a large dataset into the output of interpretable information. Hence, multivariate statistical methods were carried out to analyze physicochemical parameters in 34 rivers during a 17-year period (1997-2014). Cluster analysis divided the study area into spatially different riverine water quality sub-regions described in ascending order of water quality as severely polluted (SP), highly polluted (HP), polluted (P), moderately polluted (MP), lightly polluted (LP), and not polluted (NP). By diagnosing threats and identifying fragile zones, water contamination sources responsible for impaired water quality in the study area recognized as natural pollutants in LP, municipal wastes in P, discharge of industrial effluents in MP, natural geochemical formations in SP and HP, and superficial flows of agricultural lands in SP, HP, and MP. The dominant water type in each zone was classified into Na-Cl, Na-Cl, Na-Mg-Ca-Cl-SO₄, Na-Ca-Mg-Cl-SO₄, Na-Ca-Cl, and Ca-Mg-HCO₃-SO₄ groups for SP, HP, P, MP, LP, and NP, respectively. To explore aesthetic aspects of drinking water application, hazard quotient (HQ) was applied for children and adults in terms of ingestion and dermal exposure. Overall health risk assessment revealed the order of impacts of the secondary water quality parameters as Cl^– > Na⁺ > total dissolved solids (TDS) > Ca²⁺ > SO₄^2- > Mg²⁺. Furthermore, hazard index (HI) ranged from 0.011 to 31.439 and 0.010 to 30.122 for children and adults, respectively, indicating a potential health risk regarding chloride throughout the whole region excluding NP. To identify significant agents in water quality, principal component analysis extracted 3 varifactors (VFs), with the eigenvalues of 4.74, 1.19, and 0.85, respectively, explained about 83% of the variance. The most important parameters in the first factor were TDS, electrical conductivity, SAR, TH, Na⁺, Cl^–, and SO₄^2- accounting for 58% of the total variance. The most influenced parameters in the second and third factors were pH and HCO₃^–, respectively, with variance coverage of 26%. These factors indicated that the hydrochemical characteristics of the water originated by natural interactions (existing salt domes, evaporation, weathering, and soil erosion) and anthropogenic activities (fertilizer-rich flows of agro-fields and domestic/industrial disposals), which must be minimized in rivers to supply the population with hygienic water.

PMID:35156140 | DOI:10.1007/s10661-022-09811-1

Prog Orthod. 2022 Feb 14;23(1):5. doi: 10.1186/s40510-022-00398-4.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis aimed to critically appraise the available evidence of the effectiveness of early intervention of functional unilateral posterior crossbites (FPXB) between the ages of 6 and 12 years.

MATERIALS AND METHODS: Electronic search in four databases (PubMed, Scopus, Embase, and Google Scholar) for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) was performed between 1^st January 1990 and 31^st October 2021. Methodological index for non-randomized studies (MINORS) for CCTs and Cochrane’s risk of bias tool for RCTs were applied. The certainty of the evidence was evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) approach.

RESULTS: Nine studies (6 RCTs and 3 CCTs) were included in this review, and six of them were appropriate for quantitative synthesis. The meta-analysis revealed that the quad-helix (QH) was more effective than expansion plates (EP) in increasing the intermolar width (WMD = 1.25; 95% CI 0.75, 1.75; P < 0.001), and decreasing treatment time (WMD = – 3.36; 95% CI – 4.97, – 1.75; P < 0.001). The relapse rate at 5.6 years post-treatment was greater in the QH group than in the EP group (RR = 3.00); however, the difference was statistically insignificant. There was no significant difference between the QH and the EP in other outcome measures. When assessing the rapid maxillary expansion (RME), only one RCT compared the RME with an untreated control group and reported a significant increase in the maxillary intermolar and intercanine width (P < 0.001, P = 0.002, respectively) and a significant decrease in lower midline deviation (P < 0.001).

CONCLUSION: There is weak to moderate evidence that the treatment of functional posterior crossbite (FPXB) by the QH increased the maxillary intermolar width and the success rate and decreased the treatment duration compared to the EP. The relapse percentage was greater in the QH group. There is very weak evidence that the mandibular midline correction rate did not differ significantly between the QH and the EP modalities. The RME using the Hyrax appliance corrected the FPXB successfully; however, the strength of evidence in this regard is very low. As the quality of evidence ranged from very low to moderate in this review, we confirm the need for more RCTs with different expansion appliances in the early treatment of FPXB.

PMID:35156156 | DOI:10.1186/s40510-022-00398-4

Hosp Pediatr. 2022 Feb 14:e2021006085. doi: 10.1542/hpeds.2021-006085. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Migraine headache is a common disorder in pediatrics, sometimes leading to hospital admission. Psychiatric comorbidities are prevalent in adults with migraine headache, but there is limited evidence in the pediatric population. This study aimed to examine the prevalence of psychiatric comorbidity in children hospitalized for migraine headache and assess the association of this comorbid state on treatment interventions and outcomes.

METHODS: This multicenter, retrospective cohort study examined data from the Pediatric Health Information System. Subjects included patients aged 6 to 18 hospitalized for migraine headache between 2010 and 2018, excluding those with complex chronic conditions. Associations of psychiatric comorbidity with treatments, length of stay (LOS), cost, and 30-day readmissions were assessed using the Fisher-exact, Wilcoxon-rank-sum test, and adjusted linear or logistic regression models.

RESULTS: The total 21 436 subjects included 6796 (32%) with psychiatric comorbidity, with prevalence highest for anxiety (2415; 11.2%), depression (1433; 6.7%), and attention-deficit/hyperactivity disorder (1411; 6.5%). Patients with psychiatric comorbidity were significantly more likely (P < .001) to receive dihydroergotamine (61% vs 54%), topiramate (23% vs 18%), and valproate (38% vs 34%), and have longer mean LOS (2.6 vs 2.0 days), higher average costs ($8749 vs $7040), and higher 30-day readmission (21% vs 17%).

CONCLUSIONS: Of children hospitalized for migraine headache, 32% have comorbid psychiatric disorders associated with increased use of medications, longer LOS, and increased cost of hospitalization and readmission. Prospective studies are recommended to identify optimal multidisciplinary care models for children with migraine headaches and psychiatric comorbidities in the inpatient setting.

PMID:35156120 | DOI:10.1542/hpeds.2021-006085

Front Digit Health. 2022 Jan 26;4:833912. doi: 10.3389/fdgth.2022.833912. eCollection 2022.

NO ABSTRACT

PMID:35156082 | PMC:PMC8825497 | DOI:10.3389/fdgth.2022.833912

Front Glob Womens Health. 2022 Jan 28;2:804135. doi: 10.3389/fgwh.2021.804135. eCollection 2021.

ABSTRACT

INTRODUCTION: In Senegal, discontinuation due to sides effects of long-acting, reversible contraceptives (LARCs) is relatively low; 5% of new implant acceptors and 11% of new IUD acceptors stop using in their first year because of health or side effect concerns. This study investigated factors associated with LARC discontinuation in the first 12 months of use in Senegal and explored how LARC users cope with side effects.

METHODS: This mixed-method study involved quantitative interviews at five time points with LARC acceptors recruited from three service channels between February 2018 and March 2019. Qualitative interviews were conducted in August 2018 with a subset of those who experienced side effects. Logistic regression models identified factors associated with discontinuation due to side effects and discontinuation for any reason. Twelve-month discontinuation rates due to side effects were also estimated using a cumulative incidence function (CIF) approach to account for time to discontinuation.

RESULTS: In logistic models, method choice (IUD or implant) [OR = 3.15 (95% CI: 1.91-5.22)] and parity [OR = 0.81 (95% CI: 0.7-0.94)] were associated with discontinuation due to side effects; IUD users and women with fewer children were more likely to discontinue. Results for all-cause discontinuation were similar: method choice [OR = 2.39 (95% CI: 1.6-3.58)] and parity [OR = 0.86 (95% CI: 0.77-0.96)] were significant predictors. The 12-month side effect CIF discontinuation rate was 11.2% (95% CI: 7.9-15.0%) for IUDs and 4.9% (95% CI: 3.5-6.6%) for implants. Side effect experiences varied, but most women considered menstrual changes the least acceptable. No statistically significant differences across services channels were observed.

CONCLUSIONS: In this study in Senegal, the choice between implants and IUDs had a significant impact on continuation, and women with more children continued LARC methods longer, despite side effects.

PMID:35156087 | PMC:PMC8832161 | DOI:10.3389/fgwh.2021.804135

Patterns (N Y). 2022 Feb 9:100453. doi: 10.1016/j.patter.2022.100453. Online ahead of print.

ABSTRACT

One of the impacts of the COVID-19 pandemic has been a push for researchers to better exploit synthetic data and accelerate the design, analysis, and modelling of clinical trials. The unprecedented clinical efforts caused by COVID-19 will certainly boost future robust and innovative approaches of statistical sciences applied to clinical fields. Here, we report the development of SASC, a simple but efficient approach to generate COVID-19 related synthetic clinical data through a web application. SASC takes basic summary statistics for each group of patients and attempts to generate single variables according to internal correlations. To assess the “reliability” of the results, statistical comparisons with Synthea, a known synthetic patient generator tool and, more importantly, with clinical data of real COVID-19 patients are provided. The source code and web application are available on GitHub at https://zenodo.org/record/5896935#.Ye6cpnrMJgC.

PMID:35156066 | PMC:PMC8825316 | DOI:10.1016/j.patter.2022.100453

Schizophr Bull Open. 2022 Jan 11;3(1):sgac001. doi: 10.1093/schizbullopen/sgac001. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Schizophrenia commonly co-occurs with cardiometabolic and inflammation-related traits. It is unclear to what extent the comorbidity could be explained by shared genetic aetiology.

METHODS: We used GWAS data to estimate shared genetic aetiology between schizophrenia, cardiometabolic, and inflammation-related traits: fasting insulin (FI), fasting glucose, glycated haemoglobin, glucose tolerance, type 2 diabetes (T2D), lipids, body mass index (BMI), coronary artery disease (CAD), and C-reactive protein (CRP). We examined genome-wide correlation using linkage disequilibrium score regression (LDSC); stratified by minor-allele frequency using genetic covariance analyzer (GNOVA); then refined to locus-level using heritability estimation from summary statistics (ρ-HESS). Regions with local correlation were used in hypothesis prioritization multi-trait colocalization to examine for colocalisation, implying common genetic aetiology.

RESULTS: We found evidence for weak genome-wide negative correlation of schizophrenia with T2D (r_g = -0.07; 95% C.I., -0.03,0.12; P = .002) and BMI (r_g = -0.09; 95% C.I., -0.06, -0.12; P = 1.83 × 10^-5). We found a trend of evidence for positive genetic correlation between schizophrenia and cardiometabolic traits confined to lower-frequency variants. This was underpinned by 85 regions of locus-level correlation with evidence of opposing mechanisms. Ten loci showed strong evidence of colocalization. Four of those (rs6265 (BDNF); rs8192675 (SLC2A2); rs3800229 (FOXO3); rs17514846 (FURIN)) are implicated in brain-derived neurotrophic factor (BDNF)-related pathways.

CONCLUSIONS: LDSC may lead to downwardly-biased genetic correlation estimates between schizophrenia, cardiometabolic, and inflammation-related traits. Common genetic aetiology for these traits could be confined to lower-frequency common variants and involve opposing mechanisms. Genes related to BDNF and glucose transport amongst others may partly explain the comorbidity between schizophrenia and cardiometabolic disorders.

PMID:35156041 | PMC:PMC8827407 | DOI:10.1093/schizbullopen/sgac001

Crit Care Explor. 2022 Feb 8;4(2):e0632. doi: 10.1097/CCE.0000000000000632. eCollection 2022 Feb.

ABSTRACT

BACKGROUND: Lung protective ventilation (LPV) is a key component in the management of acute respiratory distress syndrome and other acute respiratory pathology. Initiation of LPV in the emergency department (ED) is associated with improved patient-centered and system outcomes, but adherence to LPV among ED patients is low. The impact of an ED-based ICU (ED-ICU) on LPV adherence is not known.

METHODS: This single-center, retrospective, cohort study analyzed rates of adherence to a multifaceted LPV strategy pre- and post-implementation of an ED-ICU. LPV strategy components included low tidal volume ventilation, avoidance of severe hyperoxia and high plateau pressures, and positive end-expiratory pressure settings in alignment with best-evidence recommendations. The primary outcome was adherence to the LPV strategy at time of ED departure.

RESULTS AND CONCLUSIONS: A total of 561 ED visits were included in the analysis, of which 60.0% received some portion of their emergency care in the ED-ICU. Adherence to the LPV strategy was statistically significantly higher in the ED-ICU cohort compared with the pre-ED-ICU cohort (65.8% vs 41.4%; p < 0.001) and non-ED-ICU cohort (65.8% vs 43.1%; p < 0.001). Among the ED-ICU cohort, 92.8% of patients received low tidal volume ventilation. Care in the ED-ICU was also associated with shorter ICU and hospital length of stay. These findings suggest improved patient and resource utilization outcomes for mechanically ventilated ED patients receiving care in an ED-ICU.

PMID:35156050 | PMC:PMC8826963 | DOI:10.1097/CCE.0000000000000632