Category: Statistics

Ann Neurol. 2022 May 24. doi: 10.1002/ana.26411. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer’s disease (AD).

METHODS: In this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre- and post- 60 minutes treatment with γ-tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ-tACS efficacy were evaluated.

RESULTS: We observed a significant improvement in the Rey auditory verbal learning (RAVL) test immediate recall (p<0.001) and delayed recall scores (p<0.001) after γ-tACS but not after sham tACS. Face-name associations scores improved with γ-tACS (p<0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ-tACS (p<0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ-tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus.

INTERPRETATION: Precuneus γ-tACS, able to increase γ-power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ-tACS was dependent on genetic factors and disease stage. This article is protected by copyright. All rights reserved.

PMID:35607946 | DOI:10.1002/ana.26411

Phys Ther. 2022 May 23:pzac067. doi: 10.1093/ptj/pzac067. Online ahead of print.

ABSTRACT

OBJECTIVE: The “Benchmarking in Academic Physical Therapy” study uses the PT-Graduation Questionnaire (PT-GQ) survey to develop comprehensive performance benchmarks for physical therapist education. These benchmarks facilitate interprofessional comparisons and have application to accreditation self-study reporting. The purpose of this study is to report updated benchmarks from enrollment Wave 2 of the study, with an emphasis on curricular areas that align with accreditation standards.

METHODS: Seventy Doctor of Physical Therapy (DPT) programs (26.5% national sample) administered the survey to graduates during 2020-2021. Where possible, respondent data were contextualized by statistical comparison to published medical student data (Welch’s t-test, Hedges g).

RESULTS: There were 1894 respondents who participated in the study (response rate: 63.9%). Average survey duration was 32.9 minutes. White-only, non-Hispanic/Latino/a/x individuals (78.8%) exceeded the 2020 US Census prevalence (60.1%) and only half of respondents perceived a benefit to their training from the diversity present in their programs. Over 94% of respondents indicated that their curricula were characterized by “problem solving/critical thinking” and “clinical reasoning,” but nearly half indicated “busywork” was prevalent. High curricular satisfaction ratings clustered in content areas relating to profession-specific technical skills and low ratings clustered in foundational sciences. DPT respondents reported significantly lower tolerance for ambiguity, significantly more exhaustion, and significantly less disengagement than medical students. Respondents endorsed higher levels of “adaptive” perfectionism (striving for high performance) than “maladaptive” perfectionism (concern over negative evaluations). Respondents with loans (27.7%) had debt exceeding $150,000, the benchmark above which the DPT degree loses economic power.

CONCLUSIONS: PT-GQ benchmarks revealed strengths (eg, curricula emphasizing problem solving/critical thinking and clinical reasoning) and challenges (eg, low diversity, problematic student debt) in physical therapist education.

IMPACT: Programs can use benchmarking for quality-improvement efforts and as a data source for accreditation self-study reports. The ongoing study will refine national benchmarks and pilot items to address new research questions.

PMID:35607945 | DOI:10.1093/ptj/pzac067

Hosp Pediatr. 2022 May 24:e2021006417. doi: 10.1542/hpeds.2021-006417. Online ahead of print.

ABSTRACT

OBJECTIVES: Sources of variation within febrile infant management are incompletely described. In 2016, a national standardization quality improvement initiative, Reducing Excessive Variation in Infant Sepsis Evaluations (REVISE) was implemented. We sought to: (1) describe sociodemographic factors influencing laboratory obtainment and hospitalization among febrile infants and (2) examine the association of REVISE on any identified sources of practice variation.

METHODS: We included febrile infants ≤60 days of age evaluated between December 1, 2015 and November 30, 2018 at Pediatric Health Information System-reporting hospitals. Patient demographics and hospital characteristics, including participation in REVISE, were identified. Factors associated with variation in febrile infant management were described in relation to the timing of the REVISE initiative.

RESULTS: We identified 32 572 febrile infants in our study period. Pre-REVISE, payer-type was associated with variation in laboratory obtainment and hospitalization. Compared with those with private insurance, infants with self-pay (adjusted odds ratio [aOR] 0.43, 95% confidence interval [95% CI] 0.22-0.5) or government insurance (aOR 0.67, 95% CI 0.60-0.75) had lower odds of receiving laboratories, and self-pay infants had lower odds of hospitalization (aOR 0.38, 95% CI 0.28-0.51). Post-REVISE, payer-related disparities in care remained. Disparities in care were not associated with REVISE participation, as the interaction of time and payer was not statistically different between non-REVISE and REVISE centers for either laboratory obtainment (P = .09) or hospitalization (P = .67).

CONCLUSIONS: Payer-related care inequalities exist for febrile infants. Patterns in disparities were similar over time for both non-REVISE and REVISE-participating hospitals. Further work is needed to better understand the role of standardization projects in reducing health disparities.

PMID:35607933 | DOI:10.1542/hpeds.2021-006417

J Chem Inf Model. 2022 May 24. doi: 10.1021/acs.jcim.2c00297. Online ahead of print.

ABSTRACT

The prediction and optimization of pharmacokinetic properties are essential in lead optimization. Traditional strategies mainly depend on the empirical chemical rules from medicinal chemists. However, with the rising amount of data, it is getting more difficult to manually extract useful medicinal chemistry knowledge. To this end, we introduced IDL-PPBopt, a computational strategy for predicting and optimizing the plasma protein binding (PPB) property based on an interpretable deep learning method. At first, a curated PPB data set was used to construct an interpretable deep learning model, which showed excellent predictive performance with a root mean squared error of 0.112 for the entire test set. Then, we designed a detection protocol based on the model and Wilcoxon test to identify the PPB-related substructures (named privileged substructures, PSubs) for each molecule. In total, 22 general privileged substructures (GPSubs) were identified, which shared some common features such as nitrogen-containing groups, diamines with two carbon units, and azetidine. Furthermore, a series of second-level chemical rules for each GPSub were derived through a statistical test and then summarized into substructure pairs. We demonstrated that these substructure pairs were equally applicable outside the training set and accordingly customized the structural modification schemes for each GPSub, which provided alternatives for the optimization of the PPB property. Therefore, IDL-PPBopt provides a promising scheme for the prediction and optimization of the PPB property and would be helpful for lead optimization of other pharmacokinetic properties.

PMID:35607907 | DOI:10.1021/acs.jcim.2c00297

Worldviews Evid Based Nurs. 2022 May 24. doi: 10.1111/wvn.12589. Online ahead of print.

ABSTRACT

BACKGROUND: Quality cancer care necessitates opportunities for patient participation, supposedly recognizing the individual’s preferences and experiences for being involved in their health and healthcare issues. Previous research shows that surgical cancer patients wish to be more involved, requiring professionals to be sensitive of patients’ needs.

AIMS: To explore preference-based patient participation in surgical cancer care.

METHODS: A cross-sectional study was conducted. The Patient Preferences for Patient Participation tool (4Ps) was used, which includes 12 attributes of preferences for and experiences of patient participation. Data were analyzed with descriptive and comparative statistical methods.

RESULTS: The results are based on a total of 101 questionnaires. Having reciprocal communication and being listened to by healthcare staff were commonly deemed crucial for patient participation. While 60% of the patients suggested that taking part in planning was crucial for their participation, they had experienced this only to some extent. Learning to manage symptoms and phrasing personal goals were items most often representing insufficient conditions for preference-based patient participation.

LINKING EVIDENCE TO ACTION: To support person-centered surgical care, further efforts to suffice preference-based participation are needed, including opportunities for patients to share their experiences and engage in the planning of healthcare activities.

PMID:35607906 | DOI:10.1111/wvn.12589

J Endourol. 2022 May 24. doi: 10.1089/end.2022.0103. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the oncological outcomes and recurrence patterns of clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after a template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU).

METHODS: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template of RPLND included the renal hilar and paraaortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses.

RESULTS: Compared to the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated five-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared to the group without RPLND (64.2%) (p = 0.014). The estimated five-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while a significant difference was not observed in the rate of regional LN recurrence.

CONCLUSION: This study suggests that a template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves the recurrence-free survival by reducing distant recurrences.

PMID:35607848 | DOI:10.1089/end.2022.0103

Neurol Neurochir Pol. 2022 May 24. doi: 10.5603/PJNNS.a2022.0036. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy.

CLINICAL RATIONALE: Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV’s effect on nocturnal sleep architecture.

MATERIAL AND METHODS: The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy.

RESULTS: Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance.

CONCLUSIONS: Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

PMID:35607879 | DOI:10.5603/PJNNS.a2022.0036

Stat Med. 2022 May 24. doi: 10.1002/sim.9446. Online ahead of print.

ABSTRACT

Are weak associations between a treatment and a binary outcome always sensitive to small unmeasured biases in observational studies? This possibility is often discussed in epidemiology. The familiar Mantel-Haenszel test for a $2\times 2\times S$ contingency table exaggerates sensitivity to unmeasured biases when the population odds ratios vary among the $S$ strata. A statistic built from several components, here from the $S$ strata, is said to have demonstrated insensitivity to bias if it uses only those components that provide indications of insensitivity to bias. Briefly, such a statistic is a $d$ -statistic. There are $2^S–1$ candidate statistics with $S$ strata, and a $d$ -statistic considers them all. To have level $\alpha$ , a test based on a $d$ -statistic must pay a price for its double use of the data, but as the sample size increases, that price becomes small, while the gain may be large. The price is paid by conditioning on the limited information used to identify components that are insensitive to a bias of specified magnitude, basing the test result on the information that remains after conditioning. In large samples, the $d$ -statistic achieves the largest possible design sensitivity, so it does not exaggerate sensitivity to unmeasured bias. A simulation verifies that the large sample result has traction in samples of practical size. A study of sunlight as a cause of cataract is used to illustrate issues and methods. Several extensions of the method are discussed. An R package dstat2x2xk implements the method.

PMID:35607846 | DOI:10.1002/sim.9446

BMC Res Notes. 2022 May 23;15(1):189. doi: 10.1186/s13104-022-06074-4.

ABSTRACT

OBJECTIVE: The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine.

RESULTS: Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings.

TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.

PMID:35606882 | DOI:10.1186/s13104-022-06074-4

Pilot Feasibility Stud. 2022 May 23;8(1):108. doi: 10.1186/s40814-022-01058-4.

ABSTRACT

BACKGROUND: Dietary interventions have been previously explored in children with ADHD. Elimination diets and supplementation can produce beneficial behaviour changes, but little is known about the mechanisms mediating change. We propose that these interventions may work, in part, by causing changes in the gut microbiota. A microbiome-targeted dietary intervention was developed, and its feasibility assessed.

METHODS: A non-randomised feasibility study was conducted on nine non-medicated children with ADHD, aged 8-13 years (mean 10.39 years), using a prospective one-group pre-test/post-test design. Participants were recruited from ADHD support groups in London and took part in the 6-week microbiome-targeted dietary intervention, which was specifically designed to impact the composition of gut bacteria. Children were assessed pre- and post-intervention on measures of ADHD symptomatology, cognition, sleep, gut function and stool-sample microbiome analysis. The primary aim was to assess the study completion rate, with secondary aims assessing adherence, adverse events (aiming for no severe and minimal), acceptability and suitability of outcome measures.

RESULTS: Recruitment proved to be challenging and despite targeting 230 participants directly through support groups, and many more through social media, nine families (of the planned 10) signed up for the trial. The completion rate for the study was excellent at 100%. Exploration of secondary aims revealed that (1) adherence to each aspect of the dietary protocol was very good; (2) two mild adverse events were reported; (3) parents rated the treatment as having good acceptability; (4) data collection and outcome measures were broadly feasible for use in an RCT with a few suggestions recommended; (5) descriptive data for outcome measures is presented and suggests that further exploration of gut microbiota, ADHD symptoms and sleep would be helpful in future research.

CONCLUSIONS: This study provides preliminary evidence for the feasibility of a microbiome-targeted dietary intervention in children with ADHD. Recruitment was challenging, but the diet itself was well-tolerated and adherence was very good. Families wishing to trial this diet may find it an acceptable intervention. However, recruitment, even for this small pilot study, was challenging. Because of the difficulty experienced recruiting participants, future randomised controlled trials may wish to adopt a simpler dietary approach which requires less parental time and engagement, in order to recruit the number of participants required to make meaningful statistical interpretations of efficacy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03737877 . Registered 13 November 2018-retrospectively registered, within 2 days of the first participant being recruited.

PMID:35606889 | DOI:10.1186/s40814-022-01058-4