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Collaborative biostatistics units within universities and academic medical centres operate under a wide range of different funding models; common to many of these models is the challenge of allocating time to activities that are not linked to a specific research project, such as professional development, mentorship and administrative tasks. The purpose of this paper is to describe a proposed model for 'flexible funding', that is, funding that is not linked to a specific research project, within a collaborative biostatistics unit and to detail the benefits and challenges associated with the proposed model. We present results from a qualitative study representing the perspectives of collaborative biostatisticians working under the proposed flexible funding model. In addition to providing examples of activities undertaken as part of time allocated to flexible funding, the qualitative results reveal several benefits of flexible funding both for a collaborative biostatistician (e.g., job satisfaction and professional development) and for the collaborative biostatistics unit as a whole (e.g., retention, process improvement, and leadership). [ABSTRACT FROM AUTHOR]

Background: Veterinary hospital antimicrobial stewardship (AMS) guidelines might help combat antimicrobial resistance (AMR). Objective s : Determine the conditions and types of infection for which antimicrobial drugs (AMDs) deemed critically important (CIA) by the World Health Organization (WHO) were prescribed and assess the effect of hospital AMS guidelines on adherence to International Society for Companion Animal Infectious Diseases published guidelines for the treatment of superficial bacterial folliculitis, respiratory tract disease and urinary tract infection in these cases. Animals: Dogs and cats managed at an academic veterinary hospital from 1/21 to 6/21 and 9/21 to 6/22. Methods: Prescriptions of cephalosporins (third or fourth generation), glycopeptides, macrolides/ketolides, polymyxins, and quinolones were identified. Data on culture and susceptibility (C/S) testing and previous AMD exposure were collected. Frequencies were compared between time periods using Fisher's exact test with Bonferroni corrections. Results: In animals prescribed ≥1 WHO‐CIA AMD, fluoroquinolones were the most frequently prescribed WHO‐CIA class in dogs (567/1724, 32.9%) and cats (192/450, 42.7%). No animals were prescribed carbapenems, dihydrofolate reductase inhibitors/sulfonamides, or polymyxins. No cats were prescribed aminoglycosides or amphenicols. Institutional guidelines were followed in 57.8% (324/561) cases. The most frequent causes of nonadherence were failure to perform C/S testing 46.0% (109/237) and unnecessary use of a higher‐tier AMD 43.0% (102/237). Bacterial C/S testing was more frequently performed after AMS guideline institution (59.7% vs. 46.8%, P = 0.0006). Conclusions and Clinical Importance: Adherence to published guidelines remained poor despite an increase in C/S testing. There were no changes in the frequencies of confirmed infections, positive cultures or AMD resistance between time periods. [ABSTRACT FROM AUTHOR]

Objective: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. Methods: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre‐ and post‐TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. Results: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre‐ and 5,051 in the post‐TS expansion). In the post‐TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door‐to‐needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. Interpretation: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576–582 [ABSTRACT FROM AUTHOR]

Circadian rhythms differ between young adult males and females. For example, males tend to be later chronotypes, preferring later timing of sleep and activity, than females. Likewise, there are sex differences in body composition and cardiorespiratory fitness. Few studies have investigated the association between circadian rhythms, cardiorespiratory fitness, and body composition. We sought to determine whether chronotype and circadian phase were associated with cardiorespiratory fitness, body composition, and anthropometric measures in sedentary males and females. Fifty‐nine adults participated in the study. Circadian phase and chronotype were measured using dim light melatonin onset (DLMO) and the Morningness–Eveningness Questionnaire (MEQ) score. We used peak oxygen uptake (VO2peak) results from a maximal graded exercise test to assess cardiorespiratory fitness. Body composition, BMI, and circumferences were collected as markers of adiposity. We observed a sex difference in the association between DLMO and VO2peak. For males, a later DLMO was associated with a lower VO2peak. VO2peak did not vary based on DLMO in females. Later circadian phase was also associated with increased body fat percentage, fat mass index, and abdominal circumference in males, but not females. Collectively, these results suggest that males who are later chronotypes may be at risk of obesity and low cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether baseline joint space narrowing (JSN) predicted disease remission, knee pain, and physical function changes in persons with knee osteoarthritis (OA). Methods: This study is a secondary analysis of a two‐armed randomized controlled trial. Participants were aged ≥50 years (n = 171) with a body mass index ≥28 kg/m2 and radiographic medial tibiofemoral OA. Participants in the intervention group received diet and exercise programs and special treatment (cognitive behavioral therapy, knee brace, and muscle strengthening exercises) according to the disease remission. Remission of pain and remission of patient global assessment of disease activity and/or functional impairment were used to define the disease remission. The control group were provided with an education pamphlet. The primary outcome was disease remission at 32 weeks, and the secondary outcomes were the changes in knee pain and physical function at 20 and 32 weeks. Baseline JSN was scored from 0 to 3, and the association between baseline JSN and outcomes was assessed using multiple regression. Results: There was no association of baseline JSN with disease remission at 32 weeks when the disease remission has been achieved. The baseline JSN grade 3 was associated with changes in knee pain at 20 weeks (p <.05). There was no association between baseline JSN and physical function. Conclusion: Baseline JSN severity predicted changes in knee pain but not the disease remission or changes in physical functions. Identification of baseline radiographic severity may be helpful in identifying differences in response to diet and exercise programs in knee OA. [ABSTRACT FROM AUTHOR]

Aim: Despite high‐interest rates in sex in people with hip osteoarthritis (OA), clinicians tend not to address sexual issues, especially in older adults. The objective of this study is to evaluate sexual activity and factors associated with sexual activity satisfaction in people with symptomatic hip OA. Methods: A cross‐sectional study was conducted among 252 participants with symptomatic hip OA in Australia. Quality of sex life was assessed using the online composite of sexual activities and positions questionnaires. A Poisson model with robust variance was used to calculate the prevalence ratio (PR). Factors that showed a univariate association with sexual satisfaction were then included in a multivariable model. PR with corresponding 95% confidence intervals (CI) are reported. Results: Among the 282 participants registered on the study website, 252 met the inclusion criteria, and 60.3% (152/252) completed the sexual activity questionnaires. Hip OA interfered with sexual activity in 70.0% of the participants. High confidence in completing sexual activity (PR: 0.53, 95% CI: 0.36 to 0.77) was associated with an increased prevalence ratio of sexual satisfaction. High anxiety, depression or stress during sexual activity (PR: 1.33, 95% CI: 1.10 to 1.60) was associated with an increased prevalence ratio of sexual dissatisfaction after adjusting for hip pain level and perceived partner's orgasm. Conclusion: Although a large proportion of people with hip OA remain sexually active, a substantial proportion of persons are dissatisfied with their sexual activity. Hip OA interfered with sexual activity in most participants. Psychological factors were found to be associated with sexual activity satisfaction. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study are to ascertain the determinants of quality of life (QoL) and hand function among persons with hand osteoarthritis (OA) and to assess the influence of hand function on QoL among persons with OA. Methodology: Two hundred and four participants in a clinical trial completed the baseline assessment. Demographic, socioeconomic, QoL (AqoL‐4D), hand function (Functional Index for Hand Osteoarthritis, FIHOA), pain assessment, radiographic and clinical characteristics of participants were measured using standard methods. Univariate and multivariate analyses were performed to evaluate potential associations. Results: We studied 204 participants (76% female, age 65.63 ± 8.13 years, body mass index 28.7 ± 6.5 kg/m2) with hand OA. The mean pain score of the participants on a visual analog scale was 57.8 (SD ±13.6). There was a significant, negative moderate correlation between hand function and QoL scores except for the sense domain score. Global assessment, household income and serious illness were associated with QoL (P <.001) and explained 18% of the variance of the QoL. Pain scale, Patient Global Assessment, Mental Health Score, grip strength and cyst index were associated with hand function score and explained 26% of the variance of hand function. Conclusion: The results indicate increasing impairment in hand function decreases the QoL of persons with hand OA. Some determinants were significantly associated with hand function and QoL. Determinants related to hand functions may be modifiable. In future, appropriate intervention strategies should be implemented, and further studies should be conducted to identify the effectiveness of those interventions. [ABSTRACT FROM AUTHOR]

Objective: To determine how physically active individuals are following total knee replacement (TKR) and how accurately they self‐report their step count adherence compared to objective measure following TKR. Methods: Observational cohort study, nested within the PATHway randomised‐clinical trial. Participants (n = 102) who had recently undergone TKR were recruited for the main trial. Only participant data from the intervention group were used for this study (n = 51). Participants in the intervention group received an activity tracker to monitor their physical activity and fortnightly health‐coaching sessions for 3 months. Adherence was objectively measured as percentage of steps completed divided by the amount prescribed by the health coach. Participants were asked to self‐report their adherence on a 1–10 numerical rating scale during health coaching sessions. Results: Data from 44 participants were available, resulting in a total of 224 paired measurements. Participant step count increased over the first 8 weeks of follow‐up, and plateaued from 8 weeks onwards at approximately 7500 steps/day. About two‐thirds (65.8%) of participants accurately self‐reported their step count adherence up until 12 weeks, the remaining one‐third (34.2%) underestimated their adherence. Paired t‐tests demonstrated statistically significant differences between the paired measurements from weeks 2 to 10. Discussion: Participants were generally active and completed the step goal most occasions. Two‐thirds accurately self‐reported their step goal adherence. Self‐reported measures should be combined with an objective measure of adherence for greater accuracy. A further understanding of how people engage with activity trackers can be used to promote behaviour change in physiotherapy‐led interventions. [ABSTRACT FROM AUTHOR]

Background: Acute phase proteins (APP) may guide treatment of pneumonia in dogs but correlations with radiographic abnormalities are poorly characterized. Objectives: Develop a thoracic radiographic severity scoring system (TRSS), assess correlation of radiographic changes with APP concentrations, and compare time to APP and radiograph normalization with duration of antimicrobials treatment. Animals: Sixteen client‐owned dogs, 12 with aspiration pneumonia, and 4 with community‐acquired pneumonia. Methods: Concentrations of C‐reactive protein (CRP), serum amyloid A (SAA), and haptoglobin were measured on days 1, 3, 7, 14, 28, and 60 and orthogonal 2‐view thoracic radiographs were obtained on days 1, 7, 14, 28, and 60. Treatment was clinician‐guided and blinded to APP concentrations. Radiographic severity scores were assigned by blinded, randomized retrospective review by 2 board‐certified radiologists with arbitration by a third radiologist. Results: Median (interquartile range [IQR]) time to normalization of CRP (7 days [7‐14]) and SAA concentrations (7 days [7‐14]) were shorter than antimicrobial treatment duration (17.5 days [14.5‐33.5]; P =.001 and.002, respectively) and TRSS normalization (14 days [8.8‐52], P =.02 and.02, respectively). The CRP and SAA concentrations were positively correlated with TRSS (CRP rs, 0.643; SAA rs, 0.634; both P <.0001). Both CRP and SAA identified normal thoracic radiographs area under the curve (AUC) 0.873 and 0.817, respectively, both P <.0001. Interobserver agreement for TRSS assignment was moderate (κ,.499; P <.0001). Conclusion and Clinical Importance: Concentrations of CRP and SAA normalized before radiographic resolution and before clinicians discontinued antimicrobial treatment. The CRP and SAA concentrations may guide duration of antimicrobial treatment for dogs with pneumonia. [ABSTRACT FROM AUTHOR]

Background: Prolonged antimicrobial drug (AMD) treatment is associated with antimicrobial resistance development. Biomarker measurement may aid treatment decision‐making. Objectives: Investigate temporal changes in blood biomarker concentrations in dogs undergoing treatment for pulmonary and intra‐abdominal infections; compare time to biomarker concentration normalization with duration of clinician‐directed AMD treatment. Animals: Forty‐two client‐owned dogs with pneumonia (n = 22), septic peritonitis (n = 10), or pyometra (n = 10). Methods: Plasma concentrations of C‐reactive protein (CRP), serum amyloid A (SAA), haptoglobin, procalcitonin, nucleosomes, cell‐free DNA (cfDNA), high‐mobility group box‐1 (HMGB1), CC‐motif chemokine ligand‐2 (CCL2), CXC‐motif chemokine ligand‐8 (CXCL8), and keratinocyte chemoattractant‐like (KC‐Like) were quantitated in samples collected on days 1, 3, 7, 14, 28, and 60. Treatment was directed by clinicians blinded to biomarker concentrations. Results: Concentrations of CCL2, CRP, and KC‐Like were maximal on D1, concentrations of SAA, cfDNA, HMGB1, and nucleosomes were maximal on D3 and haptoglobin concentrations were maximal on D7. These maximal concentrations were significantly different from those on D60. Concentrations of CRP and SAA decreased by 80% from peak and into respective reference intervals before AMDs were discontinued. For CRP, the median (interquartile range [IQR]) times to 20% peak and normal were 7 (6‐9) and 7 (6‐12) days, respectively, and for SAA they were 4 (4, 5) and 6 (5‐8) days, respectively, compared to a median (IQR) duration of AMD prescribing of 16 (12‐23) days (all P <.0001). Conclusions and Clinical Importance: Biomarker concentrations normalized within 7 to 14 days. Serial measurements of CRP and SAA might aid identification of disease resolution and could help guide AMD prescription decision‐making. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of ultrasound and radiographic features of thumb‐base osteoarthritis (OA) with thumb‐base pain and hand function at baseline and 12 weeks. Method: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb‐base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self‐reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12‐week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. Results: A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound‐detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. Conclusion: This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb‐base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb‐base OA. [ABSTRACT FROM AUTHOR]

Objective: To test the effectiveness of a 32-week, stepped-care intervention on disease remission rates in overweight and obese patients with medial tibiofemoral osteoarthritis (OA) compared to controls.Methods: In this randomized controlled trial, eligible participants were ≥50 years of age with a body mass index of ≥28 kg/m2 and radiographic evidence of medial tibiofemoral OA. Participants were randomized to stepped-care (n = 87) or control group (n = 84). The stepped-care group received a 2-step intervention. The first step consisted of an 18-week diet and exercise program. The second step consisted of 4 treatment subgroups: 1) diet and exercise maintenance; 2) cognitive-behavioral therapy; 3) unloader knee brace; and 4) muscle strengthening exercises. Allocation into subgroups was based on disease remission state and clinical characteristics. The primary end point was the disease remission rate (yes/no) at 32 weeks, which was reached when participants achieved the Patient Acceptable Symptom State cutoff value for pain and for the patient global assessment of disease activity and/or functional impairment.Results: Disease remission at 32 weeks was achieved by 18 of 68 (26%) in the control group and 32 of 82 (39%) in the stepped-care group (difference 12.6% [95% confidence interval -2.3, 27.4], P = 0.10). The stepped-care group showed an improvement in pain and function between baseline and 20 weeks. While functional improvement was maintained at 32 weeks, pain levels tended to get worse between weeks 20 and 32.Conclusion: The proposed intervention did not promote a significant difference in the rate of disease remission in comparison to the control group for overweight or obese patients with medial tibiofemoral OA. [ABSTRACT FROM AUTHOR]

Objective: Hand osteoarthritis (OA) trials often target exclusively the thumb base joint, although concomitant widespread interphalangeal (IP) joint involvement is frequent. We aimed to compare hand strength and function between individuals with isolated thumb base OA and those with coexistent IP joint pain and erosive OA.Methods: Baseline data from a thumb base OA trial were analyzed (n = 204). Participants were age ≥40 years with symptomatic and radiographic thumb base OA. Only the index hand was included. Self-reported IP joint pain (in any proximal, distal, or thumb IP joint), hand function score (Functional Index for Hand Osteoarthritis questionnaire [range 0-30]), and hand grip and tip-pinch strength test results were obtained at baseline. Radiographs were scored for OA severity at each joint (Kellgren/Lawrence grade) and for the presence of erosive OA at the thumb base or IP joints. Multiple linear regression was used adjusting for age, sex, body mass index, and radiographic thumb base OA severity.Results: Compared to individuals with isolated thumb base OA (62%), those with concomitant IP joint pain (17%) and erosive OA (21%) had significantly worse hand function (β = 1.82 [95% confidence interval (95% CI) 0.36, 3.28] and β = 1.47 [95% CI 0.74, 2.88], respectively). In addition, coexistence of erosive OA was independently associated with lower grip and tip-pinch strength (β = -5.14 [95% CI -7.58, -2.70] and β = -0.61 [95% CI -1.05, -0.17], respectively).Conclusion: Concomitant IP joint pain and erosive OA are associated with worse hand function in individuals with thumb base OA. Patient stratification based on these characteristics may improve the design of future thumb base OA trials. [ABSTRACT FROM AUTHOR]

Ollier disease (OD) and Maffucci syndrome (MS) are characterized by multiple enchondromas. Patients with MS also have benign vascular overgrowths that become malignant in 8.5% of cases. OD is characterized by multiple enchondromas, typically unilateral in distribution with a predilection for the appendicular skeleton. MS is characterized by multiple enchondromas bilaterally distributed in most of the cases. Both disorders feature multiple swellings on the extremity, deformity around the joints, limitations in joint mobility, scoliosis, bone shortening, leg‐length discrepancy, gait disturbances, pain, loss of function, and pathological fractures. About 50% of patients with OD or MS develop a malignancy, such as chondrosarcoma, glioma, and ovarian juvenile granulosa cell tumor. To better understand the natural history of OD and MS, we reviewed 287 papers describing patients with OD and MS. We also created a survey that was distributed directly to 162 patients through Facebook. Here, we compare the review of the cases described in the literature to the survey's responses. The review of the literature showed that: the patients with OD are diagnosed at a younger age; the prevalence of chondrosarcomas among patients with OD or MS was ~30%; in four patients, vascular anomalies were identified in internal organs only; and, the prevalence of cancer among patients with OD or MS was ~50%. With these data, health care providers will better understand the natural history, severity, and prognosis of these diseases and the prevalence of malignancies in these patients. Here, we recommend new guidelines for the care of patients with OD and MS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between hip injury/giving way and hip pain exacerbations in patients with symptomatic hip osteoarthritis (OA).Methods: We conducted an internet-based case-crossover study to assess hip injury and giving way for hip pain exacerbation. Eligible participants with symptomatic hip OA were followed up for 90 days and asked to complete online questionnaires at baseline and 10-day intervals (control periods). They also logged on to the study web site to complete questionnaires for an episode of a hip pain exacerbation (case periods) defined as an increase of 2 points in pain intensity compared with the baseline rating on a numeric rating scale (range 0-10). The relationship of hip injury and giving way to the risk of pain exacerbation was examined using conditional logistic regression.Results: Of 252 patients recruited into the study, we included 133 patients (53%) who provided data from both case and control periods. Hip injury during the last 7 days increased the risk of hip pain exacerbation (odds ratio [OR] 2.74 [95% confidence interval (95% CI) 1.62-4.62]). The hip giving way during the last 2 days was associated with an increased risk of hip pain exacerbation (OR 2.10 [95% CI 1.30-3.39]) and showed a significant relationship between the number of hip giving way events and the risk of hip pain exacerbations (P < 0.001).Conclusion: Hip injury and episodes of the hip giving way were significantly related to pain exacerbation in patients with symptomatic hip OA. Methods to prevent exposure to injury may help to reduce the burden of pain in patients with hip OA. [ABSTRACT FROM AUTHOR]

Background & Aims: Advances in direct‐acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked‐to‐care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. Methods: Using a modelling approach grounded in Italian real‐life data of diagnosed and treated patients, different linkage‐to‐care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. Results: Under the 40% linked‐to‐care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948‐1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0‐F3 cases. Under the 60% linked‐to‐care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958‐1978 birth cohorts could capture 55% of F0‐F3 individuals. Under the 80% linked‐to‐care scenario, screening limited in 1968‐1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. Conclusion: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required. [ABSTRACT FROM AUTHOR]

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH. [ABSTRACT FROM AUTHOR]