Threshold For Clinical Significance Research Articles

Comparison of Marker-Based RSA and CT-RSA for Analyzing Micromotions After Distal Radius Osteotomy: A 1-Year Retrospective Study of 24 Patients.

Radiostereometric Analysis (RSA) is the most accurate method for determining early micromotions of orthopedic implants. Computed Tomography Radiostereometric Analysis (CT-RSA) is a method that can be used to determine implant and bone micromovements using low-dose CT scans. This study aimed to evaluate the reliability of the CT-RSA method in measuring the interfragmental mobility in patients who have undergone a correction osteotomy due to a malunited distal radius fracture. Twenty-four patients were included and operated with a radiolucent volar plate. Markers were embedded in the plate and bone. RSA and CT examinations were obtained postoperatively up to 1-year postoperative. Micromovements of the distal radius segment relative to the proximal were compared between the methods with paired analysis and Bland-Altman plots. The limits of clinical significance were: dorsal/volar tilt < 10°, radial shortening < 5 mm, radial inclination ≥ 15°, and radial shift < 5 mm. For the dorsal/volar tilt, the paired analysis between the two methods, showed a mean difference (95% CI) of -0.06° (-0.67 to 0.55), for radial compression-0.04 mm (-0.09 to 0.01), for radial inclination 0.21° (-0.06 to 0.48), and for radial shift -0.07 mm (-0.21 to 0.07). The paired analysis for micromotions showed that the thresholds of clinical significance are excluded from the difference's 95% CI. The Bland-Altman plots showed comparable results up to 1 year, considering clinically relevant thresholds. In conclusion, the CT-RSA method is comparable to that of marker-based RSA in measuring micromotions after wrist osteotomy, as the differences between the methods are not clinically significant.

Do Patient-Answered Versus Caregiver-Answered Patient-Reported Outcomes Differ in Pediatric Upper Extremity Fracture Care?

Patient-reported outcomes in children can be assessed using self-report or caregiver proxy-report; however, self-reported and proxy-reported outcomes often vary between respondents, a phenomenon called cross-informant variance. This phenomenon has not been studied in pediatric fracture care. This study compares self-reported and proxy-reported patient-reported outcomes in children being treated for upper extremity fractures. Children aged 8 to 17 with upper extremity fractures completed pediatric self-report questionnaires and their caregivers completed parent proxy-report questionnaires composed of items from three Patient-Reported Outcomes Measurement Information System (PROMIS) domains (Physical Function-Upper Extremity, Psychological Stress Experiences, and Pain-Interference). Mean patient and caregiver T-scores for each domain were compared using paired T-tests. Correlation between scores was assessed using scatterplots and Pearson correlation coefficient. Agreement between child and caregiver T-scores was assessed using Bland-Altman plots. One hundred child-caregiver dyads were included. Patients' mean age was 12.3 years, and 68% were male. Statistically significant differences were found between mean patient and caregiver T-scores in all PROMIS domains. Caregivers overestimated patient pain and psychological stress and underestimated upper extremity function. However, only the disagreement in the Pain-Interference domain met the threshold of clinical significance, a difference of three or more T-score points. Bland-Altman analysis revealed proportional bias in the Psychological Stress Experiences and Pain-Interference domains. With higher T-scores, caregivers tended to overestimate psychological stress to a greater extent but tended toward agreement with their children for pain. This study identified cross-informant variance between children and caretakers in the setting of pediatric upper extremity fractures. Although notable differences were observed in all PROMIS domains included, only one met the level of clinical significance, suggesting that not all domains are equally susceptible to child-caretaker disagreement. As patient-reported outcomes become more used in pediatric settings, the possibility of cross-informant variance must be considered when choosing to use self-report or proxy-report instruments. Level III.

Protocol for a systematic review with meta-analysis and trial sequential analysis of preventive interventions versus any control intervention for parents with a mental disorder on offspring outcomes

BackgroundOffspring of parents with a mental disorder are at high risk of a range of adverse outcomes, highlighting the need for preventive interventions. However, a comprehensive overview of the beneficial and harmful effects of preventive interventions for parents with mental disorders on offspring outcomes are uncertain. The main objective of this systematic review will be to assess the effects of preventive interventions versus any control intervention for parents with a mental disorder on offspring outcomes.Methods/designWe will conduct a systematic review with meta-analysis and report it as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, trial sequential analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. To identify relevant trials, we will search for published trials in several electronic databases from their inception to the present. We will also search for unpublished trials and grey literature. Two review authors will independently screen the articles, extract data, and perform a risk of bias assessment. We will include any published or unpublished randomized clinical trial comparing a psychological preventive intervention versus any control intervention for parents with any mental disorder. The primary outcomes will be quality of life and incidence of a mental disorder. Secondary outcomes will include internalizing symptoms, externalizing symptoms, serious adverse events, out-of-home placement, and absence from school or daycare. Exploratory outcomes include trauma, socioemotional development, and language development. All outcomes will be assessed in offsping only.DiscussionThere is an urgent need for a comprehensive, updated systematic review of the beneficial and harmful effects of preventive interventions for children of parents with a mental disorder. The findings of this systematic review are expected to provide evidence-based information for policymakers, clinicians, and researchers to help them make informed decisions about the most effective interventions and guide future research for this highly prevalent population.Systematic review registrationPROSPERO CRD42023463421.

Risk and protective factors of late in-the-bag intraocular lens dislocations: systematic review.

To identify and review published articles addressing risk and protective factors of late in-the-bag (ITB) intraocular lens (IOL) dislocations. Prevention of this complication is of great importance considering the great number of cataract cases and its vision-threatening capacity. A structured search on PubMed (MEDLINE) using both Medical Subject Headings and key words was conducted. In addition, the reference lists of the resulting articles were screened for further publications. Articles were eligible if they included 20 or more patients. Hazard and odds ratios were analyzed if they were calculated in the original study. The relative frequency of risk factors was recorded if hazard or odds ratios were not available. The threshold for clinical significance was set at 10%. Risk-of-bias in individual studies was evaluated using the revised Cochrane risk-of-bias tool in randomized trials (RoB 2.0) and the Cochrane risk-of-bias in nonrandomized studies of intervention tool. Database search identified 3474 records, and no further records were obtained from the reference lists. After exclusion of records not related to the topic, 177 articles were assessed for eligibility. Of these, 39 were considered eligible and read in full. 3 studies were prospective, while all other investigations were retrospective. In total, 18 614 cases of late ITB dislocations were analyzed across all studies. The risk of bias within studies was considerable because only 3 studies were prospective and statistical significance of risk factors was assessed in only 5 studies. Typical patient age of this condition is between 70 and 85 years, and there seems to be a slight male predominance. Risk factors with a good level of evidence include preoperative trauma and zonular dehiscence, previous vitrectomy, retinitis pigmentosa, pseudoexfoliation, high myopia, glaucoma/previous glaucoma surgery, corneal endothelial damage, and uveitis. Hydrophilic, quadripode, and haptic-angulation IOLs are further risk factors. Capsular tension rings, Nd:YAG capsulotomy, 3-piece IOLs, and IOLs with large optic diameters protect from ITB dislocations. Typically, no risk factors can be identified in approximately one-fourth of patients.

The minimal important difference in obsessive-compulsive disorder: An analysis of double-blind SSRI trials in adults.

The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

Pain experience with outpatient hysteroscopy: A prospective cohort study

BackgroundAbnormal uterine bleeding (AUB) affects women of all ages and is one of the most common reasons for referral to a gynaecological clinic. Operative hysteroscopic procedures allow for a see-and-treat approach to AUB, and these techniques have been shown to be feasible and acceptable in the outpatient setting. ObjectiveTo assess if there is an increase in pain scores for women who are undergoing an operative hysteroscopic procedure with Myosure LITE® (Hologic; mechanical hysteroscopic tissue removal system) compared to outpatient diagnostic hysteroscopy alone. Study designA prospective cohort study was performed. All participants attending the outpatient hysteroscopy clinic at Mercy Hospital for Women completed a pre-and post-procedure questionnaire. This included a visual analogue scale (VAS) for any pre-existing pain, anticipated pain, and actual pain experienced during procedure. Factors influencing overall satisfaction and willingness to attend again were also assessed. Data was entered into RedCap® for analysis. A difference in VAS of 10 mm or more was considered clinically significant. An alpha of p < 0.05 was assigned for statistical significance. ResultsBetween February 2020 and November 2022, 208 women underwent outpatient diagnostic hysteroscopy followed by an operative hysteroscopy with MyoSure®. To allow for standardisation of analgesia, only participants who had a cervical block before their Myosure® procedure were included for analysis (n = 111). There was statistical evidence (t(111) = 2.36, p = 0.02) of a lower mean VAS pain score for operative Myosure (36.5 mm, 95 % CI: 31.1–41.8 mm) compared to outpatient diagnostic hysteroscopy (44.1 mm, 95 % CI: 39.0–49.2 mm). The mean difference in VAS pain score was estimated as 7.7 mm (95 % CI: 1.2–14.1 mm) lower for Myosure compared to hysteroscopy. Given the threshold for clinical significance was considered as 10 mm difference in VAS, the variance in pain scores is under the likely clinically significant range. There was no significant difference in pain scores for diagnostic hysteroscopy with or without paracervical block (mean difference = 1.42; 95 % CI: −6.35 to 9.20). There was no association between pre-existing pain, and actual pain for hysteroscopy, or Myosure (p = 0.997 and p = 0.065 respectively). The anticipated pain score was weakly associated with actual pain during the operative Myosure procedure (p = 0.02), and with outpatient diagnostic hysteroscopy (p = 0.019). ConclusionOutpatient hysteroscopy procedures are generally well tolerated. The pain experience with operative Myosure was less than that reported during the diagnostic hysteroscopy by the same patient although this is unlikely of clinical significance. Importantly, Myosure was not more painful than the initial diagnostic procedure, and most patients were satisfied with the outcome and would choose to have the procedure again in an outpatient setting. This is in keeping with other studies which have shown a high degree of patient tolerance and satisfaction with this approach.

Comparison of digital study model superimposition methods using implant-supported crowns and best-fit algorithms

Research regarding orthodontic changes using the superimposition of digital study models (DSMs) is commonplace. Information regarding the accuracy of data processing by superimposition software is limited. The study aimed to compare different methods of superimposing DSMs using implant-supported crowns (ISC) as a stable reference structure. DSMs containing ISCs were sourced from a database of patients treated with clear aligner therapy. The DSM representing the planned treatment outcome was superimposed on the pretreatment DSM. Three tooth points were selected for comparison on the contralateral side of each ISC. Differences in Cartesian coordinates for each tooth point for each arch superimposition method, used by the Geomagic Control X(3D systems, Rock Hill, NC) software system, were recorded. Paired t tests for the reference standard superimposition method best-fit high-resolution using the entire dental arch compared with initial, best-fit low-resolution, and best-fit high-resolution using the ISC only were calculated. The DSMs of 54 dental arches containing ISCs were evaluated. All mean differences for displacements of selected points on the contralateral side to the ISC in the 3 Cartesian planes were<0.05 mm (P<0.05) and below the threshold of clinical significance. In addition, the standard superimposition techniques (initial, best-fit low-resolution, and best-fit high-resolution) resulted in nonstatistically significant and nonclinically significant differences in the position of the ISC. Researchers can be confident that the described superimposition methodologies, with and without ISCs as a stable reference structure, are a valid method for accurately assessing most intraarch dental changes.

Impact of implant design on the Forgotten Joint Score: a retrospective study comparing two contemporary knee designs.

This retrospective study was designed to assess two fixed bearing total knee design concepts and their clinical outcomes, particularly in Forgotten Joint Score-12 (FJS-12). Patients were assessed clinically using the Knee Society Score (KSS). Participants completed an FJS-12 and a short form of the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS). A total of 216 knees -76 with Genesis II and 150 with Vanguard total knee arthroplasties - were included. Patients in the Vanguard group had significantly better postoperative FJS-12 scores (by 10.1 points, p = 0.019). Differences in KSS subscores also reached the level of statistical significance. KOOS-PS did not differ significantly. Statistically significant differences between the two knee designs on FJS-12, KS and FS assessments were revealed, but overall, these differences may not reach the threshold of clinical significance.

Dosimetric impact of contour editing on CT and MRI deep-learning autosegmentation for brain OARs.

To establish the clinical applicability of deep-learning organ-at-risk autocontouring models (DL-AC) for brain radiotherapy. The dosimetric impact of contour editing, prior to model training, on performance was evaluated for both CT and MRI-based models. The correlation between geometric and dosimetric measures was also investigated to establish whether dosimetric assessment is required for clinical validation. CT and MRI-based deep learning autosegmentation models were trained using edited and unedited clinical contours. Autosegmentations were dosimetrically compared to gold standard contours for a test cohort. D1%, D5%, D50%, and maximum dose were used as clinically relevant dosimetric measures. The statistical significance of dosimetric differences between the gold standard and autocontours was established using paired Student's t-tests. Clinically significant cases were identified via dosimetric headroom to the OAR tolerance. Pearson's Correlations were used to investigate the relationship between geometric measures and absolute percentage dose changes for each autosegmentation model. Except for the right orbit, when delineated using MRI models, the dosimetric statistical analysis revealed no superior model in terms of the dosimetric accuracy between the CT DL-AC models or between the MRI DL-AC for any investigated brain OARs. The number of patients where the clinical significance threshold was exceeded was higher for the optic chiasm D1% than other OARs, for all autosegmentation models. A weak correlation was consistently observed between the outcomes of dosimetric and geometric evaluations. Editing contours before training the DL-AC model had no significant impact on dosimetry. The geometric test metrics were inadequate to estimate the impact of contour inaccuracies on dose. Accordingly, dosimetric analysis is needed to evaluate the clinical applicability of DL-AC models in the brain.

Transcranial Doppler cerebrovascular reactivity: Thresholds for clinical significance in cerebrovascular disease.

Thresholds for abnormal transcranial Dopplercerebrovascular reactivity (CVR) studies are poorly understood, especially for patients withcerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR). CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation.The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp). A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SDage 55±16years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. TheCO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn=.73, Sp=.79), CT/MRI perfusion abnormality (Sn=.42, Sp=.77), infarction on MRI (Sn=.45, Sp=.76), and pressure-dependent exam (Sn=.50, Sp=.76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn=.46, Sp=.94), infarction on MRI (Sn=.27, Sp=.94), and pressure-dependent exam (Sn=.31, Sp=.90). In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. NoninvasiveCVR may aid in diagnosing and risk stratifying patients withstenosis.

The Acute Effect of Chamomile Intake on Blood Coagulation Tests in Healthy Volunteers: A Randomized Trial.

Chamomile administration may have desirable effects in the perioperative setting. Current practice, however, discourages perioperative chamomile use due to a theoretical increase in bleeding. Therefore, we evaluated if chamomile acutely (within 4 h of ingestion) prolongs coagulation assays. Eight healthy volunteers were randomized to receive 2 interventions in a crossover design: (a) single dose of chamomile extract capsule (500 mg) and (b) single dose of chamomile tea (3 g in 150 mL water). Interventions were separated at least 3 days apart from each other. Blood was sampled pre-ingestion, 2 h post-ingestion, and 4 h post-ingestion for each intervention. The primary outcome was the maximal change in prothrombin time (PT) before vs after each intervention. Secondary outcomes included changes in international normalized ratio, activated partial thromboplastin time, thrombin time, reptilase time, and fibrinogen levels. All 8 subjects completed the study. The average pre-ingestion PT values for tea and capsules were 11.9 (1.1) s and 12.0 (0.9) s, respectively. Tea significantly increased the average maximum PT by 0.7 (0.2) s (P = 0.0078). Extract capsules increased the maximum PT by 0.3 (0.2) s (P = 0.06). Neither PT prolongation met the predefined 10% threshold for clinical significance. No significant changes in secondary outcomes were observed. Chamomile tea ingestion prolongs PT. However, the clinical significance of this is unclear at this time and warrants further investigation. ClinicalTrials.gov Registration Number: NCT05272475.

Adjuvant misoprostol or mifepristone for cervical preparation with osmotic dilators before dilation and evacuation

ObjectivesThis study aimed to compare effectiveness and safety of cervical preparation with osmotic dilators plus same-day misoprostol or overnight mifepristone prior to dilation and evacuation (D&E). Study designWe conducted a retrospective cohort analysis of 664 patients initiating abortion between 18 and 22 weeks at an ambulatory health center. We abstracted medical record data from two consecutive 12-month periods in 2017 to 2019. All patients received overnight dilators plus: 600 mcg buccal misoprostol 90 minutes before D&E (period 1); 200 mg oral mifepristone at time of dilators (period 2). Our primary outcome was procedure time. We report frequency of patients experiencing any acute complication, defined as unplanned procedure (i.e., reaspiration, cervical laceration repair, uterine balloon tamponade) or hospital transfer and bleeding complications. ResultsWe observed higher mean procedure time in the mifepristone group (9.7 ± 5.3 minutes vs 7.9 ± 4.4, p = 0.004). After adjusting for race, ethnicity, insurance, body mass index, parity, prior cesarean, prior uterine surgery, gestational age, provider, trainee participation, and long-acting reversible contraception initiation, the difference remained statistically significant (relative change 1.09, 95% CI 1.01, 1.17) but failed to reach our threshold for clinical significance. The use of additional misoprostol was more common in the mifepristone group, but the use of an additional set of dilators was not different between groups. Acute complications occurred at a frequency of 4.1% in misoprostol group and 4.3% in mifepristone group (p = 0.90). ConclusionsWe found procedure time to be longer with adjunctive mifepristone compared to misoprostol; however, this difference is unlikely to be clinically meaningful. Furthermore, the frequency of acute complications was similar between groups. ImplicationsOvernight mifepristone at the time of cervical dilator placement is a safe and effective alternative to adjuvant same-day misoprostol for cervical preparation prior to D&E and may offer benefits for clinic flow and patient experience.

1 Psychometric comparison of the long and short forms of the Personality Assessment Inventory in a neuropsychiatric population

Objective:The Personality Assessment Inventory (PAI; Morey, 1991; 2007) is a 344 item self-report measure of personality, psychopathology, and factors affecting treatment. The PAI short form (PAI-SF) contains the first 160 items of the PAI and is often favoured as a screening tool or brief version to mitigate respondent burden and fatigue. The PAI has been psychometrically validated among numerous populations (Slavin-Mulford et al., 2012), while psychometric research on the PAI-SF is gradually emerging. The psychometric properties of the PAI-SF range from adequate to strong in psychiatric (Sinclair et al., 2009), forensic (Sinclair et al., 2010), outpatient and nonclinical (Ward et al., 2018), and stroke (Udala et al., 2020) samples. To advance research validating the PAI-SF among diverse populations, this project investigated the psychometric comparability between the PAI and the PAI-SF in a neuropsychiatric population. Based on previous literature, it was hypothesized that the PAI-SF would produce congruent results to the PAI in this sample.Participants and Methods:For this study, participant files (N=214) were collected retrospectively from short- and long-term residential psychiatric and substance use treatment facilities in Minnesota for patients with neurological and cognitive concerns referred for neuropsychological evaluation. The PAI-SF was scored using the first 160 items from a patient’s long-form PAI protocol. To determine the psychometric comparability of long- and short-forms, paired-samples t-tests, intraclass correlations, and percent agreement in clinical classification between forms were analyzed.Results:Analyses of participant data found that intra-class correlations ranged from .87 to .98 for each subscale on the PAI when compared to the PAI-SF, demonstrating good to excellent reliability between forms. Symptoms are considered clinically elevated when they exceed the clinical significance threshold for a subscale (typically a T-score of 70+). Agreement between the PAI and PAI-SF subscales in the classification of clinically elevated scores ranged from 86% to 100%. When forms did not agree, the PAI-SF was more likely to be clinically significant relative to the PAI. A comparison of subscale means between forms was examined by independent samples T-tests with a Bonferroni correction. Results revealed significant differences between the PAI and PAI-SF on one validity scale (Negative Impression Management), three clinical scales (Anxiety; Depression; Antisocial Features), and one treatment scale (Treatment Rejection).Conclusions:Results demonstrated that the PAI and PAI-SF have high reliability between forms in a neuropsychiatric population. Although mean scores differed on a small number of subscales between the PAI and PAI-SF, differences did not appear sufficiently large enough to shift clinical classifications, as the two forms performed similarly in their identification of clinically elevated scales. Findings align with previous literature and suggest that the PAI-SF may perform adequately in a neuropsychiatric population if brevity or participant burden is of concern. However, caution is warranted when making clinical decisions with the PAI-SF as more research is needed.

Values derived from patient reported outcomes in spine surgery: a systematic review of the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state.

While patient reported outcome measures (PROMs) define value in spine surgery, several values such as minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptom state (PASS) help guide the interpretation of PROMs and identify thresholds of clinical significance. Significant variation exists in reported values and their calculation, so the primary objective of this study was to systematically review the spine surgery literature for metrics of clinical significance derived from PROMs. We conducted a query of PubMed/MEDLINE and Scopus databases from inception to January 1, 2023, for studies that derived quantitative metrics (e.g., SCB, MCID, PASS) from PROMs in the setting of spine surgery with minimum 1-year follow-up. Details regarding the specific PROMs were collected including which PROM was measured, whether anchor- or distribution-based methods were utilized, the specific calculations, and the recommended value for a given PROM based on all evaluated calculations. Thirty-seven studies of 21,780 patients were included. The most commonly evaluated PROM-derived value was the MCID (n = 28), followed by PASS (n = 6) and SCB (n = 4). Twenty-one studies only utilized anchor-based calculations, 15 utilized both anchor-based and distribution-based methods, and one only utilized distribution-based calculations. The most commonly evaluated legacy PROMs were the Oswestry Disability Index (ODI) (N = 11, MCID range 4-20) and visual analog scale back pain (N = 5, MCID range 0.5-4.6). All 10 studies that derived SCB or PASS utilized the receiver operating characteristic methods. Among the six studies deriving a PASS value, four only evaluated ODI, identifying PASS ranging from 5 to 22. While calculated measures of clinical significance such as MCID, PASS, and SCB exist, significant heterogeneity exists in the current literature. Current shortcomings include a wide variability of reported value thresholds across the literature, and limited applicability to more heterogenous patient populations than the targeted cohorts included in published investigations. Continued investigations that apply these methods to heterogenous, large-scale populations can help increase generalizability and validity of these measures. III.

Bispectral Index Changes Following Boluses of Commonly Used Intravenous Medications During Volatile Anesthesia Identified From Retrospective Data.

Although patients are commonly monitored for depth of anesthesia, it is unclear to what extent administration of intravenous anesthetic medications may affect calculated bispectral (BIS) index values under general anesthesia. In a retrospective analysis of electronic anesthesia records from an academic medical center, we examined BIS index changes associated with 14 different intravenous medications, as administered in routine practice, during volatile-based anesthesia using a novel screening approach. Discrete-time windows were identified in which only a single drug bolus was administered, and subsequent changes in the BIS index, concentration of volatile anesthetic, and arterial pressure were analyzed. Our primary outcome was change in BIS index, following drug administration. Adjusted 95% confidence intervals were compared to predetermined thresholds for clinical significance. Secondary sensitivity analyses examined the same outcomes, with available data separated according to differences in baseline volatile anesthetic concentrations, doses of the administered medications, and length of time window. The study cohort was comprised of data from 20,170 distinct cases, 54.7% of patients were men, with a median age of 55. In the primary analysis, ketamine at a median dose of 20 mg was associated with a median (confidence limits) increase in BIS index of 3.8 (2.5-5.0). Midazolam (median dose 2 mg) was associated with a median decrease in BIS index of 3.0 (1.5-4.5). Neither of these drug administrations occurred during time periods associated with changes in volatile anesthetic concentration. Analysis for dexmedetomidine was confounded by concomitant decreases in volatile anesthetic concentration. No other medication analyzed, including propofol and common opioids, was associated with a significant change in BIS index. Secondary analyses revealed that similar BIS index changes occurred when midazolam and ketamine were administered at different volatile anesthetic concentrations and different doses, and these changes persisted 11 to 20 minutes postadministration. Modest, but persistent changes in BIS index occurred following doses of ketamine (increase) and midazolam (decrease) during periods of stable volatile anesthetic administration.

Fetal Echocardiographic Z Score Pilot Project: Study Design and Impact of Gestational Age and Variable Type on Reproducibility of Measurements Within and Across Investigators

Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives. Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated measures for 12 fetuses. Kruskal-Wallis tests were used to compare measurements across centers and age groups. Coefficients of variation (CoVs) were calculated at the subject level for each measurement as the ratio of SD to mean. Intraclass correlation coefficients were used to show inter- and intrarater reliabilities. Cohen's d>0.8 was used to define clinically important differences. Measurements were plotted against gestational age, biparietal diameter, and femur length. Expert raters completed each set of measurements in a mean of 23±9 min/fetus. Missingness ranged from 0% to 29%. CoVs were similar across age groups for all variables (P<.05) except ductus arteriosus mean velocity and left ventricular ejection time, which were both higher at older gestational age. CoVs were >15% for right ventricular systolic and diastolic widths despite fair to good repeatability (intraclass correlation coefficient>0.5); ductal velocities and two-dimensional measures, left ventricular short-axis dimensions, and isovolumic times all had high CoVs and high interobserver variability despite good to excellent intraobserver agreement (intraclass correlation coefficient>0.6). CoVs did not improve when ratios (e.g., tricuspid/mitral annulus) were used instead of linear measurements. Overall, 27 variables had acceptable inter- and intraobserver repeatability, while 14 had excessive variability between readers despite good intraobserver agreement. There is considerable variability in fetal echocardiographic quantification in clinical practice that may affect the design of multicenter fetal echocardiographic Z score studies, and not all measurements may be feasible for standard normalization. As missingness was substantial, a prospective design will be needed. Data from this pilot study may aid in the calculation of sample sizes and inform thresholds for distinguishing clinically significant from statistically significant effects.

Association between calculated panel reactive antibody and waitlist outcomes in the 2018 heart allocation system

The impact of heart transplant (HT) waitlist candidate sensitization on waitlist outcomes in the US is unknown. Adult waitlist outcomes in OPTN (October 2018-September 2022) by calculated panel reactive antibody (cPRA) were modeled to identify thresholds of clinical significance. The primary outcome was the rate of HT by cPRA category (low: 0-35, middle: >35-90, high: >90) assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). The secondary outcome was waitlist removal for death or clinical deterioration. The elevated cPRA categories were associated with lower rates of HT. Candidates in the middle (35-90) and high cPRA categories (>90) had an adjusted 24% lower rate (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.80-0.92) and 61% lower rate (HR 0.39 95% CI. 0.33-0.47) of HT than the lowest category, respectively. Waitlist candidates in the high cPRA category listed in the top acuity strata (Statuses 1, 2) had increased rates of delisting for death or deterioration compared to those in the low cPRA category (adjusted HR 2.9, 95% CI 1.5-5.5), however, elevated cPRA (middle, high) was not associated with an increased rate of death and delisting when the cohort was considered as a whole. Elevated cPRA was associated with reduced rates of HT across all waitlist acuity tiers. Among HT waitlist candidates listed at the top acuity strata, the high cPRA category was associated with increased rates of delisting due to death or deterioration. Elevated cPRA may require consideration for critically ill candidates under continuous allocation.

Diagnostic significance of instrumental and manual methods for quantitative assessment of lower limb difference (review of literature)

This article provides a review of the scientific literature over the past 30 years on the assessment of the anatomical or ‘true’ difference in leg length (structural Limb Length Discrepancy, sLLD), as well as a summary of our own clinical experience on this issue.Purpose. Carrying out a systematic analysis of publications on methods for assessing the anatomical difference in leg length and the diagnostic significance of its detection in order to provide highly effective care to patients with diseases of the musculoskeletal system.Materials and methods. The study presents a description of modern hardware and manual methods for assessing sLLD, the shortcomings of their isolated use, and substantiates the need for a comprehensive examination of patients with sLLD with a combination of manual and hardware diagnostic methods.Results and discussion. The results of observations patients with various diseases of the musculoskeletal system and comorbid neurological symptoms are presented. Examples of postural radiographs of patients with anatomical difference in leg length after arthroplasty are given; with persistent functional shortening of the limb of traumatic origin. The possibilities of differentiated correction of pain syndromes of musculoskeletal origin under the influence of an anatomically short leg on pelvic skew, scoliosis in the form of lift therapy, and the possibility of manual correction in upslip functional dysfunction are considered.Conclusions. An unrecognized and not timely compensated structural difference in the length of the legs is one of the main causes of asymmetries in posture, increased fatigue and chronic pain of the musculoskeletal system, as well as a consequence of subjectivity, insufficient reliability and accuracy of many direct methods proposed in the literature for quantifying the difference in leg size. The low threshold of clinical significance of sLLD, along with the wide prevalence of this phenomenon in the population, dictates the need for increased diagnostic alertness of specialists in order to provide effective assistance to this group of patients through the combined use of pharmacotherapy, manual techniques and adequate orthopedic correction

Bi-planar calibration method for templating of hip joint arthroplasty: phantom study and proof of concept

PurposeCalibration of radiographs is a critical step in digital templating for hip arthroplasty. Calibration errors of > 1.5% lead to over- or undersizing of the templated implants and may affect logistics and patient safety. Contemporary calibration methods are known to be imprecise with average errors of 6.5% and wide variance. A novel bi-planar radiograph-based calibration method is proposed, and a phantom study was conducted as proof of concept.MethodsA spherical external calibration marker (ECM) is placed in front of the pubic symphysis of a pelvic bone model at twelve different positions. For each marker position, standard anteroposterior radiographs and four corresponding lateral radiographs with different degrees of rotation (0°–30°) are taken (overall, 60 radiographs). Calibration factors are calculated for an internal calibration marker (ICM) at the centre of the right hip (reference) and the ECM using a novel algorithm. Rotation and marker positions simulate foreseeable use errors and misplacements and aim to test robustness of the method against these errors.ResultsECM calibration factor was 125.9% (range 124.7–127.2), and the mean ICM calibration factor was 126.6% (range 126.2–127.1) (p<0.001). Four images (8.3%) were beyond the 1% error threshold (all with 30° rotation). The mean difference was 0.79% (SD 0.49).ConclusionThe bi-planar method precisely predicts the true calibration factor of the hip joint plane under various conditions. In lateral radiographs, rotation of up to 20° did not adversely affect the precision and all images had calibration errors below the threshold for clinical significance.

Patient-Reported Outcome Measures in Chemotherapy-Induced Peripheral Neurotoxicity: Defining Minimal and Clinically Important Changes.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common complication of cancer treatment that produces functional disability. Increasingly, patient-reported outcome measures (PROMs) are used to assess CIPN, providing a broader symptom perspective than clinician-graded scales. Understanding when a reported change in CIPN symptoms meets the threshold for clinical significance is challenging. This study aimed to provide interpretation guidelines for validated CIPN PROMs, and thereby enable estimation of thresholds to identify clinically relevant symptoms. Patients commencing neurotoxic cancer treatments were assessed at 3 timepoints: baseline, midtreatment, and end-of-treatment. Trajectory of CIPN development was assessed by means of CIPN PROMs, EORTC Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity questionnaire (FACT/GOG-NTX). Thresholds were estimated for CIPN PROMs using the NCI CTCAE sensory neuropathy scale as the clinical anchor by midtreatment and end-of-treatment. Patients were assigned to a clinical change group according to CIPN development: either no development; grade 1 neuropathy (minimally important difference [MID]); or grade 2 neuropathy (clinically important difference). Distribution-based estimates (SD, 0.5) were also evaluated as supportive evidence. In total, 406 patients were recruited to the study, of whom 62% (n=199/320) developed CIPN by midtreatment and 80% (n=274/343) by end-of-treatment. Anchor-based MID estimates by midtreatment were 5.06 (95% CI, 4.26-5.86) for the QLQ-CIPN20 and 3.54 (95% CI, 2.87-4.20) for the FACT/GOG-NTX. End-of-treatment MIDs were estimated to be 7.32 (95% CI, 6.23-8.40) for the QLQ-CIPN20 and 4.84 (95% CI, 3.98-5.70) for the FACT/GOG-NTX. Distribution-based MID estimations yielded lower values than anchor-based methods, at 3.73 for the QLQ-CIPN20 and 2.64 for the FACT/GOG-NTX at midtreatment and 5.52 for the QLQ-CIPN20 and 3.64 for the FACT/GOG-NTX at end-of-treatment. Findings from the present series aid meaningful interpretation for commonly used validated CIPN PROMs and provide thresholds that serve as guidance on how to interpret score changes, which will be useful for design and evaluation of clinical trials and clinical practice.