Preoperative photography improves patient satisfaction following hallux valgus surgery.

BACKGROUND: Patient satisfaction is variable following hallux valgus (HV) surgery. This prospective, blinded, randomized trial endeavored to determine whether showing patients a preoperative photograph would improve satisfaction following HV corrective surgery. METHODS: Adult patients undergoing HV surgery were randomized to a picture group (P) or a no picture group (NP). P-group patients were shown their preoperative photograph for 5 min at each postoperative visit. Outcome measures included the Foot Function Index (FFI), the Foot Ankle Outcome Score (FAOS), and a patient satisfaction questionnaire. RESULTS: Twenty-nine patients were enrolled in the study (15P, 14 NP). At 3, and 6 months postoperatively, patients in the P-group were more likely to be completely satisfied with the appearance of their foot. There were no differences between groups with respect to postoperative HVA, IMA, or FFI, and FAOS scores. CONCLUSION: Patient satisfaction is increased following hallux valgus corrective surgery by reminding patients of the preoperative appearance of their foot through the use of photographs. LEVEL OF EVIDENCE: Level I, randomized control trial.

The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain.

OBJECTIVE: To assess the analgesic efficacy and safety of single-dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain. DESIGN: Randomised, double blinded, placebo-controlled clinical trial. SETTING: The tertiary emergency department of Austin Hospital, Melbourne. PARTICIPANTS: Patients who presented with acute, non-traumatic low back pain between 21 May 2018 and 13 June 2019. INTERVENTION: One hundred eligible patients were randomised to receiving 400 mg CBD or placebo in addition to standard emergency department analgesic medication. MAIN OUTCOME MEASURES: Pain score two hours after administration of study agent, on a verbal numerical pain scale (range, 0-10). Secondary outcomes were length of stay, need for rescue analgesia, and adverse events. RESULTS: The median age of the 100 participants was 47 years (IQR, 34-60 years); 44 were women. Mean pain scores at two hours were similar for the CBD (6.2 points; 95% CI, 5.5-6.9 points) and placebo groups (5.8 points; 95% CI, 5.1-6.6 points; absolute difference, -0.3 points; 95% CI, -1.3 to 0.6 points). The median length of stay was 9.0 hours (IQR, 7.4-12 hours) for the CBD group and 8.5 hours (IQR, 6.5-21 hours) for the placebo group. Oxycodone use during the four hours preceding and the four hours after receiving CBD or placebo was similar for the two groups, as were reported side effects. CONCLUSION: CBD was not superior to placebo as an adjunct medication for relieving acute non-traumatic low back pain in the emergency department. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000487213 (prospective).

Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders.

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.

Impaction fractures of the anterior tibial plafond: Outcomes after fractures around the ankle: Is the anterior impaction plafond fracture a problem?

OBJECTIVES: To determine whether patients with AO/OTA 43-B anterior impaction tibial plafond fractures have worse clinical outcomes, and an increased risk of progression to ankle arthrodesis. DESIGN: Retrospective cohort study. SETTING: Level 1 academic trauma center. PATIENTS: One hundred sixty-eight patients were included in the study, all of whom had tibial plafond fractures. INTERVENTION: Study patients underwent external fixation and/or open reduction internal fixation (ORIF) as indicated by fracture/injury pattern. MAIN OUTCOME MEASUREMENTS: Arthrodesis rate. RESULTS: AO 43-B Anterior impaction tibial plafond fractures have an increased risk of progression to arthrodesis when compared to AO 43-B nonanterior impaction type fractures (19.4% vs 8%). CONCLUSIONS: AO 43-B anterior impaction tibial plafond fractures have a worse clinical outcome compared to AO 43-B nonanterior impaction fractures. These fractures also confer increased risk of progression to arthrodesis. CONFLICTS OF INTEREST: The authors have no conflict of interests to declare.

Biomechanical Consequences of Nail Insertion Point and Anterior Cortical Perforation for Antegrade Femoral Nailing.

This biomechanical study assessed the influence of changing antegrade cephalomedullary nail insertion point from anterior to neutral to posterior locations relative to the tip of the greater trochanter with or without anterior cortical perforation in the distal femur. Artificial osteoporotic femurs and cephalomedullary nails were used to create 5 test groups each with 8 specimens: intact femur without a nail or perforation, anterior nail insertion point without perforation, neutral nail insertion point without perforation, posterior nail insertion point without perforation, and posterior nail insertion point with perforation. Nondestructive biomechanical tests were done at 250 N in axial, coronal 3-point bending, sagittal 3-point bending, and torsional loading in order to measure overall stiffness and bone stress. The intact femur group vs. all femur/nail groups had lower stiffness in all loading modes (p ≤ 0.018), as well as higher bone stress in the proximal femur (p ≤ 0.027) but not in the distal femur above the perforation (p = 0.096). Compared to each other, femur/nail groups only showed differences in sagittal 3-point bending stiffness for anterior and neutral vs. posterior nail insertion points without (p ≤ 0.025) and with perforation (p ≤ 0.047). Although it did not achieve statistical significance (p ≥ 0.096), moving the nail insertion point from anterior to neutral to posterior to posterior with perforation did gradually increase bone stress by 45% (proximal femur) and 46% (distal femur). No femur or hardware failures occurred. Moving the nail insertion point and the presence of a perforation had little effect on stiffness, but the increased bone stress may be important as a predictor of fracture. Based on current bone stress results, surgeons should use anterior or neutral nail insertion points to reduce the risk of anterior cortical perforation.

Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial.

OBJECTIVE: There is increasing recognition that, in men, some biological actions attributed to testosterone (TS) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess the effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short-term biological effects of E2 add-back without increasing circulating TS. DESIGN: 28-day randomised, placebo-controlled trial. METHODS: 37 participants were randomised to either 0.9 or 1.8 mg of 0.1% E2 gel per day or matched placebo gel. Fasting morning serum hormones, quality of life questionnaires, and treatment side effects were evaluated at baseline, days 14 and 28. Hot flush diaries and other biochemical measurements were completed at baseline and study end. RESULTS: Transdermal E2 significantly raised serum E2 from baseline to day 28 compared to placebo in the 0.9 mg dose group (median: 208 pmol/L; interquartile range: 157-332) and in the 1.8 mg dose group (median: 220 pmol/L; interquartile range: 144-660). E2 treatment reduced hot flush frequency and severity as well as beta carboxyl-terminal type 1 collagen telopeptide. CONCLUSION: In men with castrate levels of E2 and TS, daily transdermal E2: 0.9-1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test whether low-dose E2 treatment can mitigate ADT-associated adverse effects without E2-related toxicity.

Randomized Controlled Trial of Melatonin for Sleep Disturbance in Dravet Syndrome: The DREAMS Study.

STUDY OBJECTIVES: Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome. We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome. METHODS: A double-blind crossover randomized placebo-controlled trial was conducted, comparing 6 mg regular-release melatonin to placebo for patients with Dravet syndrome and sleep disturbance. The primary outcome measure was total sleep measured by actigraphy, with secondary outcomes including wakefulness after sleep onset (WASO), Sleep Disturbance Scale in Children and Quality of Life in Children with Epilepsy 55 questionnaires, caregiver reports of clinical change, seizure diary and serum antiepileptic drug levels. We also compared actigraphy data of patients with Dravet syndrome to an age-matched healthy control group. RESULTS: A total of 13 patients completed the study. There was no difference in total sleep or WASO between melatonin and placebo. However, of the 11 patients for whom caregivers reported a clear clinical difference between treatments (blinded), 8 reported improvement on melatonin (P < .05). Interestingly, when compared to patients in the control group, patients with Dravet syndrome had significantly increased total sleep (P = .002). CONCLUSIONS: Melatonin did not increase total sleep; however, blinded caregiver reports indicate treatment with melatonin provided considerable clinical benefit for some patients with Dravet syndrome and sleep disturbance. CLINICAL TRIAL REGISTRATION: Registry: Australian Government Department of Health, Therapeutic Goods Administration under the Clinical Trials Notification Scheme (protocol number 2241).

Precision therapy for epilepsy due to KCNT1 mutations: A randomized trial of oral quinidine.

OBJECTIVE: To evaluate quinidine as a precision therapy for severe epilepsy due to gain of function mutations in the potassium channel gene KCNT1. METHODS: A single-center, inpatient, order-randomized, blinded, placebo-controlled, crossover trial of oral quinidine included 6 patients with severe autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) due to KCNT1 mutation. Order was block randomized and blinded. Four-day treatment blocks were used with a 2-day washout between. Dose started at 900 mg over 3 divided doses then, in subsequent participants, was reduced to 600 mg, then 300 mg. Primary outcome was seizure frequency measured on continuous video-EEG in those completing the trial. RESULTS: Prolonged QT interval occurred in the first 2 patients at doses of 900 and 600 mg quinidine per day, respectively, despite serum quinidine levels well below the therapeutic range (0.61 and 0.51 µg/mL, reference range 1.3-5.0 µg/mL). Four patients completed treatment with 300 mg/d without adverse events. Patients completing the trial had very frequent seizures (mean 14 per day, SD 7, median 13, interquartile range 10-18). Seizures per day were nonsignificantly increased by quinidine (median 2, 95% confidence interval -1.5 to +5, p = 0.15) and no patient had a 50% seizure reduction. CONCLUSION: Quinidine did not show efficacy in adults and teenagers with ADNFLE. Dose-limiting cardiac side effects were observed even in the presence of low measured serum quinidine levels. Although small, this trial suggests use of quinidine in ADNFLE is likely to be ineffective coupled with considerable cardiac risks. CLINICAL TRIALS REGISTRATION: Australian Therapeutic Goods Administration Clinical Trial Registry (trial number 2015/0151). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for persons with severe epilepsy due to gain of function mutations in the potassium channel gene KCNT1, quinidine does not significantly reduce seizure frequency.

Automated Bone Age Analysis with Lossy Image Files.

BACKGROUND: In our U.S. Department of Defense hospital system, pediatric endocrinology and radiology resources to evaluate bone age radiographs are limited. Our tertiary care center provides expert specialty support to remotely stationed beneficiaries at more than 30 Department of Defense medical facilities using a well-established, asynchronous, Health Insurance Portability and Accountability Act compliant system that allows for physician-to-physician teleconsultation. Up to 14% of these teleconsultations are for endocrinology assessment, many of which include bone age analysis. We sought to evaluate the feasibility of using an automated bone age analysis program using the file format most commonly provided to us, lossy JPEG image files saved at lower quality, to improve access to our consultation services. METHODS: All patients seen in the Tripler Army Medical Center pediatric endocrinology clinic, who were being evaluated for poor growth during the 2-month study period and who had a bone age film performed at Tripler Army Medical Center during that time, were eligible to have their deidentified bone age films analyzed. We imported lossy JPEG bone age image files from our hospital web viewer to BoneXpert, version 2.1, using a fully automated, custom built system that reconstructed each file's true resolution and then packaged the original image into a Digital Imaging and Communications in Medicine header. The original JPEG files were saved at 70% quality. Bone age readings were compared between our pediatric endocrinologists (ENDO), pediatric radiologists (RADS), and BoneXpert (BONE). Additionally, adult height prediction from ENDO and BONE were compared. FINDINGS: 35 bone age images were evaluated over a 2-month period. Most patients were being evaluated for idiopathic short stature or growth hormone deficiency. Analysis of variance showed no significant differences in mean bone age readings between the 3 groups (mean bone age reading = 9.0, 9.1, and 9.1 years for ENDO, RADS, and BONE, respectively, p = 0.827). Mean (SD) differences between physician and software bone age readings were -0.09 (0.89) years (ENDO) and -0.03 (1.01) years (RADS). Mean difference for adult height predictions was only -0.2 cm (p = 0.806). DISCUSSION: Automated analysis of lossy JPEG files of bone age images using the BoneXpert software appears to be feasible and accurate. Larger studies are needed to validate these results.

A novel method for determining hepatic sinusoidal oxygen permeability in the isolated perfused rat liver using [15O]O2.

Measurement of hepatic sinusoidal permeability of oxygen and other substrates may help elucidate the mechanisms responsible for impaired liver function in cirrhosis. However studies of sinusoidal oxygen permeability in normal liver and various disease states have been limited due to the considerable technical difficulties involved in the use of standard techniques. We have developed a new method for measuring sinusoidal oxygen permeability in the isolated perfused rat liver that overcomes the difficulties of previous methods by using [(15)O]O(2) and an in-line fluid monitor. This method uses data obtained from impulse response curves of radiolabelled red cells, albumin and oxygen that are fitted mathematically using the axial dispersion model to yield rate constants that describe oxygen transit through the liver. We have demonstrated the utility and reproducibility of this method by comparing multiple injections and permeability determinations in the same preparation. This approach could be used in isolated perfused organs to study oxygen permeability in a range of disease states.

Root surface area of the mandibular cuspid and bicuspids.

BACKGROUND: The purpose of this study was to determine the total root surface area of extracted teeth by computerized image analysis and the amount of remaining attachment area assuming various amounts of bone loss due to periodontal disease. METHODS: One hundred fifty extracted mandibular teeth were evaluated, and measured from cusp tip to the cemento-enamel junction (CEJ), CEJ to root apex, and cusp tip to root apex. The fulcrum point of the tooth was also measured, along with the total root surface area of attachment and total surface area of attachment remaining following simulation of attachment loss in 2 mm increments. Measurements were made on 80 teeth on one proximal surface and either the buccal or lingual surface and multiplied by a factor of 2. Measurements on 70 teeth were made on all 4 root surfaces to predict the accuracy of measuring only 2 surfaces to determine root surface area. Images of the tooth surfaces were obtained by video camera and converted to computer image with measurement of the surface areas. RESULTS: The total root surface area for the mandibular cuspids and first and second bicuspids was 275.88 mm2, 251.45 mm2, and 271.81 mm2, respectively. The 2-sided and 4-sided measurements for the mandibular first bicuspid were 252.55 mm2 and 247.02 mm2, respectively (P>0.05). CONCLUSIONS: This study found the total root surface area to be greater than that in most previous studies. Increasing attachment loss is related to decreasing root surface area; however, this relationship is not directly proportional. No statistical difference was found between measuring 4 surfaces versus only 2 surfaces.

A review of factors affecting vaccine preventable disease in Japan.

Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded "routine" (eg, polio, pertussis) and self-pay "voluntary" groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion.

Extensive clinical experience: a simple guide to basal insulin adjustments for long-distance travel.

Long-distance travel across multiple time zones presents unique challenges for patients taking insulin, requiring adjustments in both timing and dosage of basal insulin when several times zones (≥5) are traversed. Travel across the International Date Line adds to the confusion, as existing resources and dosing calculators often do not account for the date change. We review recommendations from available guidelines and dosage calculators used for long-distance travel basal insulin adjustments and then present our patient handouts which allow for a safe, specific, single dose adjustment for eastward and westward travel. The included handouts are easy to use and can be freely reproduced for use in diabetes clinics.