Real world practices of luspatercept at an academic medical center.

Introduction: Luspatercept is approved for patients with very low-to intermediate-risk myelodysplastic syndrome (MDS). Dosing is based on pre-dose hemoglobin levels and transfusion requirements. This study aims to evaluate if a site with a pharmacist prospectively reviewing luspatercept doses achieves dose optimization, compared to a site that does not have a pharmacist prospectively reviewing doses. Methods: We performed a retrospective chart review involving patients age ≥18 years or older with MDS at a major academic medical center main campus, which does not have a pharmacist prospectively review luspatercept doses, and a satellite campus infusion center, which has a pharmacist prospectively reviewing doses. Patients included received at least one dose of luspatercept between January 1, 2017 through August 31, 2022. The primary endpoint is the percentage of off-label luspatercept doses not consistent with prescribing information (PI) recommended dose adjustments. Results: The study included 17 patients. Of the 162 doses evaluated, 37 (23%) were off-label. Off-label dosing at the main campus was more common than at a satellite location (29.6% vs. 2.4%; p < 0.003). More patients achieved transfusion independence at the satellite compared to the main campus (83.3% vs. 27.3% p < 0.39). Conclusions: There was a higher percentage of off-label dosing at a center without a pharmacist's prospective review vs. a center with a pharmacist's prospective review. On-label dose optimization may lead to a higher percentage of patients achieving transfusion independence. Enhancements in the current ordering and review process can be improved with the involvement of a pharmacist's prospective involvement at both centers.

Early and intensive motor training to enhance neurological recovery in people with spinal cord injury: trial protocol.

STUDY DESIGN: Protocol for a multi-centre randomised controlled trial (the SCI-MT trial). OBJECTIVES: To determine whether 10 weeks of intensive motor training enhances neurological recovery in people with recent spinal cord injury (SCI). SETTING: Fifteen spinal injury units in Australia, Scotland, England, Italy, Netherlands, Norway, and Belgium. METHODS: A pragmatic randomised controlled trial will be undertaken. Two hundred and twenty people with recent SCI (onset in the preceding 10 weeks, American Spinal Injuries Association Impairment Scale (AIS) A lesion with motor function more than three levels below the motor level on one or both sides, or an AIS C or D lesion) will be randomised to receive either usual care plus intensive motor training (12 h of motor training per week for 10 weeks) or usual care alone. The primary outcome is neurological recovery at 10 weeks, measured with the Total Motor Score from the International Standards for Neurological Classification of SCI. Secondary outcomes include global measures of motor function, ability to walk, quality of life, participants' perceptions about ability to perform self-selected goals, length of hospital stay and participants' impressions of therapeutic benefit at 10 weeks and 6 months. A cost-effectiveness study and process evaluation will be run alongside the trial. The first participant was randomised in June 2021 and the trial is due for completion in 2025. CONCLUSIONS: The findings of the SCI-MT Trial will guide recommendations about the type and dose of inpatient therapy that optimises neurological recovery in people with SCI. TRIAL REGISTRATION: ACTRN12621000091808 (1.2.2021).

Fibro-Osseous Lesions Of The Craniofacial Complex In Horses: 30 Cases (2001-2019).

OBJECTIVE: To describe the presentation, diagnosis, treatment, and outcome for horses with fibro-osseous lesions of the craniofacial complex. STUDY DESIGN: Retrospective multicenter case series. ANIMALS: Thirty horses evaluated for fibro-osseous lesions of the skull from January 1, 2001 through December 31, 2019 in four centers. METHODS: Medical records were reviewed for signalment, clinical presentation, histological and diagnostic imaging findings, treatment instituted, and outcome. Long-term outcome information was obtained by owner questionnaire or the medical record. RESULTS: Diagnoses included ossifying fibroma in 20 of 30 horses, osteoma in eight of 30 horses, and fibrous dysplasia in two of 30 horses. Twelve of 30 lesions were diagnosed in horses <1 year old, and 20 of 30 lesions originated from the rostral mandible. The most common treatment was rostral mandibulectomy. Recurrence was not reported after complete excision. Incomplete excision was confirmed in eight horses (four ossifying fibromas, three osteomas, and one fibrous dysplasia), and follow-up information was available for seven horses. Recurrence occurred in one horse, while six horses had long-term resolution of clinical signs. Prognosis for survival and return to use was excellent in 23 horses with long-term follow-up. CONCLUSION: Fibro-osseous lesions were uncommon in this multicenter study; they were most commonly diagnosed in young animals and most frequently affected the rostral mandible. Long-term survival was excellent. CLINICAL SIGNIFICANCE: The definitive diagnosis of fibro-osseous lesions of the craniofacial complex in horses is made from results of histopathology and cannot be determined on the basis of clinical presentation alone. Surgical excision is indicated, and prognosis can be favorable even when complete surgical margins are not obtained.

Radiation safety practices among Canadian equine veterinary workers during diagnostic procedures with portable X-ray equipment.

The objective of this study was to report observed radiation safety practices among equine workers using portable X-ray units at 3 veterinary practices in Canada. Practice 1 was comprised of equine field service workers from an academic institution, whereas Practices 2 and 3 were comprised of workers from private equine referral practices. Out of 2969 exposure-worker observations, protective aprons were worn for > 99% (2968/2969), thyroid shields for 87% (2584/2969), and eyeglasses for 10% (310/2969). The cassette was held by hand for 97% (1078/1114) of observations, and the X-ray unit was held by hand for 100% (1293/1293) of observations. Gloves were used for 54% (606/1114) and < 1% (5/1293) of observations involving cassette holders and X-ray tube operators, respectively. Use of gloves was more frequent among technologists than DVMs (P = 0.004), and among workers in Practices 1 and 3 than in Practice 2 (P < 0.001). In conclusion, given that workers commonly hold cassettes and X-ray tubes by hand, improvement in shielding use is needed. Consideration should be given to specific behavior recommendations in radiation regulations.

Pratiques de radioprotection chez les travailleurs vétérinaires équins canadiens pendant les procédures de diagnostic avec un équipement de radiographie portable. L'objectif de la présente étude était de rapporter les pratiques de radioprotection observées chez les travailleurs équins utilisant des appareils de radiographie portatifs dans trois pratiques vétérinaires au Canada. La pratique 1 était composée de travailleurs équins sur le terrain d'une institution universitaire, tandis que les pratiques 2 et 3 étaient composées de travailleurs sur le terrain issus de pratiques de référence équines privées. Sur 2969 observations de travailleurs exposés, des tabliers de protection ont été portés pour > 99 % (2968/2969), des écrans thyroïdiens pour 87 % (2584/2969) et des lunettes pour 10 % (310/2969). La cassette a été tenue à la main pour 97 % (1078/1114) des observations et l'unité de radiographie a été tenue à la main pour 100 % (1293/1293) des observations. Des gants ont été utilisés pour 54 % (606/1114) et < 1 % (5/1293) des observations impliquant des porteurs de cassette et des opérateurs de tubes à rayons X, respectivement. L'utilisation de gants était plus fréquente chez les technologues que chez les vétérinaires (P = 0,004) et chez les travailleurs des Pratiques 1 et 3 que ceux de la Pratique 2 (P < 0,001). En conclusion, étant donné que les travailleurs tiennent généralement des cassettes et des tubes à rayons X à la main, une amélioration de l'utilisation du blindage est nécessaire. Il faudrait tenir compte des recommandations de comportement spécifiques dans les réglementations relatives aux rayonnements.(Traduit par Dr Serge Messier).

Will the real Moebius syndrome please stand up? A systematic review of the literature and statistical cluster analysis of clinical features.

Moebius syndrome is a highly variable syndrome with abducens and facial nerve palsy as core features. Strict diagnostic criteria do not exist and the inconsistency of the associated features makes determination difficult. To determine what features are associated with Moebius syndrome we performed a systematic literature review resulting in a composite case series of 449 individuals labeled with Moebius syndrome. We applied minimum criteria (facial and abducens palsy) to determine the prevalence of associated clinical features in this series. Additionally, we performed statistical cluster analysis to determine which features tended to occur together. Our study comprises the largest series of patients with Moebius syndrome and the first to apply statistical methodology to elucidate clinical relationships. We present evidence for two groups within the Moebius diagnosis. Type 1: exhibiting micrognathia, limb anomalies and feeding/swallowing difficulty that tend to occur together. Type 2: phenotypically diverse but more associated with radiologically detectable neurologic abnormalities and developmental delay.

Cross-sectional survey study to examine underuse of twice daily inhaled maintenance therapy among patients with asthma.

Objective: Anecdotal evidence suggests that some patients with asthma intentionally use their twice-daily (BID) inhaled controller therapy once daily (QD), thus not achieving optimal dosing levels. This study identified the prevalence of and factors associated with intentional QD use of BID-indicated controllers among adult patients with asthma. Methods: This was a cross-sectional survey study of adults using inhaled controllers intended for BID dosing for treatment of asthma and/or COPD. Survey responses were linked to administrative claims data for the prior 12 months (baseline). Results of patients indicating both an asthma diagnosis and current intentional QD or BID use of controllers are presented. Results: Of 1401 patients with asthma, 30.9% reported intentional QD use of their controller and 69.1% reported BID use. Intentional QD use was mostly a function of patients' lack of perceived need for BID treatment (44.1%) or physician orders to take their controller QD (34.0%). Patients reporting intentional QD use tended to be healthier (higher health status scores, and lower Charlson comorbidity scores, ambulatory and ER visits, and healthcare costs) with better asthma control (lower asthma-related ER and ambulatory visits and rescue medication use, and higher Asthma Control Test scores) compared with patients reporting BID use. Conclusions: Perceptions regarding health and the necessity of controller use to control or treat asthma were the main drivers of medication-taking behavior. Patients with less severe asthma were more likely to report once daily use of their inhaled controller, but still maintained asthma control.

Effects of systemic corticosteroids on blood eosinophil counts in asthma: real-world data.

Introduction: Systemic corticosteroids (SCS) are effective anti-inflammatory therapies for patients with severe or persistent asthma. Use of SCS reduces blood eosinophil counts; the magnitude and duration of reduction in real-world settings needs further investigation. Objective: To examine the SCS effect on blood eosinophil counts over time among patients with asthma in a real-world setting. Methods: This retrospective study used Reliant Medical Group (Worcester, MA) electronic medical records between January 2011 and December 2015. Patients aged ≥12 years with ≥1 SCS prescription (first: index date), ≥1 asthma diagnosis, and ≥1 eosinophil count in each 12-month pre- and post-index periods were included for the study. Endpoints included SCS treatment patterns, time to SCS discontinuation, and changes in index blood eosinophil counts (≥150, ≥300, and ≥400 cells/µL) with SCS initiation and discontinuation. Results: At index visit, 642 of 1198 included patients had a blood eosinophil count ≥150 cells/µL. After an average initial SCS prescription of 35 mg/day, mean (% change) eosinophil counts at month 1 in the ≥150, ≥300, and≥400 cells/µL subgroups decreased from index by 112 (-30%), 202 (-34%), and 290 (-36%) cells/µL, respectively. Of the patients with an eosinophil count ≥150 cells/µL at index, who discontinued SCS within 7, 14, or 21 days after the index date, 21%, 26%, and 25% had an eosinophil count <150 cells/µL 1-month post-index, respectively. Conclusion: Blood eosinophil counts decreased following initiation of SCS therapy and had not returned to index levels several weeks after SCS discontinuation. The time frame of SCS discontinuation is an important consideration when identifying patients with eosinophilic asthma.

Safety and efficacy of Holmium laser enucleation of the prostate (HoLEP) in patients with previous transperineal biopsy (TPB): outcomes from a dual-centre case-control study.

BACKGROUND: We investigated the surgical feasibility, safety and effectiveness of 50 W (low power) Holmium Laser enucleation of the prostate (HoLEP) in patients who have undergone previous template biopsy of the prostate (TPB). METHODS: Data encompassing pre-operative baseline characteristics, intra-operative measures and post-operative outcomes was collected for 109 patients undergoing HoLEP across two UK centres. Patients were stratified into two groups; group 1 (n = 24) had undergone previous TPB were compared with 'controls' (no previous TPB) in group 2 (n = 85). The primary outcome was successful HoLEP. RESULTS: There were no statistically significant differences in either key baseline characteristics or mass of prostate enucleated between groups 1 and 2. There was no statistically significant difference in enucleation or morcellation times parameters between the two groups other than enucleation efficiency in favour of group 1 (p = 0.024). Functional outcomes improved, without any statistically significant difference, in both groups. CONCLUSIONS: In patients with a previous TPB, HoLEP is surgically feasible, safe and effective. TPB should not be considered a contraindication to HoLEP. Our work provides a strong foundation for further research in this area.

Disease burden in patients with asthma before initiating biologics: A retrospective cohort database study.

Background: Real-world data on the characteristics and burden of disease among patients with asthma before receiving asthma-specific biologics would improve the understanding of the use of these therapies in a clinical setting. Currently, limited data are available on the use of mepolizumab and omalizumab for the treatment of asthma. Objective: To determine the characteristics and disease burden among patients with asthma before initiating treatment with mepolizumab or omalizumab. Methods: This was a retrospective cohort analysis of commercial and Medicare Advantage Plan members from a medical claims database with a new claim for mepolizumab or omalizumab between January 1, 2015, and March 31, 2017 (GSK ID: HO-17-18283). Eligible patients had a diagnosis of asthma and continuous enrollment in the health plan, with clinical and pharmacy benefits for 12 months before initiating asthma-specific biologic treatment (baseline period), and no diagnosis of chronic idiopathic urticaria during the baseline period. Patient characteristics, exacerbations, and asthma-related health care resource utilization and costs were assessed during the baseline period. Results: Overall, 188 and 901 patients prescribed mepolizumab and omalizumab, respectively, were included. In the 12 months before initiating asthma-specific biologic therapy, the patients prescribed mepolizumab were older, had higher blood eosinophil counts, more-frequent exacerbations (2.9 versus 2.0 exacerbations/year; p < 0.001), and more inhaled corticosteroid and systemic corticosteroid use compared with those prescribed omalizumab. Overall, asthma-related health-care resource utilization and costs were similar across both treatment cohorts, although patients prescribed mepolizumab had more pharmacy fills, higher pharmacy costs, and lower clinic costs compared with patients prescribed omalizumab (20.8 versus 16.9 fills, $4504 versus $3102, and $1816 versus $2709, respectively; all p < 0.001). Conclusion: In the 12 months before initiating asthma-specific biologic therapy, the patients prescribed mepolizumab may have a greater disease burden than those prescribed omalizumab. Overall, health-care resource utilization and costs were broadly similar across both treatment cohorts.

Adaptation and evaluation of a monopolar electrosurgical triangle-tip knife for transendoscopic ventriculocordectomy in healthy horses.

OBJECTIVE: To evaluate the efficacy and safety of a transendoscopic monopolar electrosurgical triangle-tip knife as instrumentation to perform unilateral ventriculocordectomy (VC) in healthy adult horses. STUDY DESIGN: In vivo experimental study. STUDY POPULATION: Nine horses donated for medical conditions unrelated to respiratory system. METHODS: The triangle-tip knife was applied in contact fashion. Left VC was performed under standing sedation. Endoscopic images of the upper airway were graded for inflammation by 2 masked surgeons preoperatively and immediately, 24 hours and, in 2 cases, 7 and 14 days postoperatively. Four larynxes were examined for histological evidence of inflammation and collagen deposition at 24 hours (n = 2) and at 14 days (n = 2) after surgery. RESULTS: Ventriculocordectomy was successfully performed in all horses. Endoscopic evidence of inflammation was scored as normal (preoperatively), mild (immediately postoperatively), mild (24 hours postoperatively), mild (7 days postoperatively), and normal (14 days postoperatively). According to histopathology, inflammation of the surgical site and ventricularis muscle was generally increased (variable is common and is present in most high-power fields) 24 hours and 14 days postoperatively. Fibrosis and collagen deposition also seemed increased at the surgical site 14 days postoperatively. CONCLUSION: Ventriculocordectomy was successfully performed with an electrosurgical triangle-tip knife and resulted in acceptable short-term outcomes. CLINICAL SIGNIFICANCE: The use of an electrosurgical triangle-tip knife alternative instrumentation may be offer an alternative option to perform VC in practices when diode laser is not available or is cost prohibitive. Longer term evaluation of the VC site is required to determine the effect on rima glottic cross-sectional area.

Symptomatology following traumatic brain injury in a multidisciplinary clinic: experiences from a tertiary centre.

BACKGROUND: Physical, cognitive and emotional sequelae in patients with traumatic brain injury (TBI) have been identified; some as late as two years post-injury. To aid in the specialist management of such patients, a multidisciplinary neurotrauma clinic was initiated at a tertiary centre.  Aim: This study sought to describe the clinical features of patients who attended the clinic. METHODS: Patient data was collected under several categories: basic demographics, mechanism and severity of injury, initial CT findings and management, hospital stay and discharge details, symptoms in clinic and actions performed by clinic staff (medication changes, referrals to other services, etc.). RESULTS: Three hundred and five patients met the inclusion criteria. Mean age was 47.5 and most patients were male (72.1%). Commonest mechanism of injury was falls (53.1%). 17.4% of injuries were classed as mild, 68.2% moderate and 14.1% severe. Commonest injury locations were frontal (21.6%) and temporal (16.1%) with contusions (37.4%) and subdural hematomas (27.9%) the commonest type of injury on initial CT scan. The most frequent physical complaints were headache (47.9%) and memory problems (42.0%). 7.9% complained of new seizures since TBI. 41.6% were referred to further services: most frequently psychology (19.3%) and neuropsychiatry (18.4%). Of 184 known to be employed before their injury, 48.4% of these returned to work before their last appointment. 28.5% were unable to continue driving. CONCLUSION: Our study provides an insight into the reality of long term sequelae of TBI, especially those at the more severe end of the spectrum, who are likely to present to tertiary or specialist services. Information gathered in this study about characteristics of the TBI population and their outcomes allows for better targeting of suitable patients for referral to a multidisciplinary clinic and improved resource planning.

Internal neurolysis of the maxillary branch of the trigeminal nerve for the treatment of equine trigeminal mediated headshaking syndrome.

A 5-year-old Hannovarian warmblood gelding was presented for recurrent headshaking exacerbated with exercise. The horse displayed clinical signs of repetitive vertical head movements, face rubbing on the forelimbs and on the ground, repetitive sneezing, and striking the muzzle with his forelimbs. The clinical signs resulted in a horse that could not be ridden and was dangerous. Clinical signs were most persistent in direct sunlight, but occurred with excitement, exercise, or bridling indoors. A diagnosis of equine trigeminal mediated headshaking syndrome was made. Surgical treatment was performed with a supraorbital approach to the maxillary branch of the trigeminal nerve as it exits the round foramen, where an internal neurolysis (nerve combing) was conducted on both the left and right nerves. Severe headshaking behavior resolved after surgery. The horse displayed face rubbing of the muzzle which began 96 hours after surgery and resolved over 12 days with corticosteroid and vitamin E therapy. The horse became pasture sound and the clinical signs had resolved in the presence of sunlight, but repetitive vertical head movements persisted under saddle which left the horse unpleasant to ride.

Neurolyse interne de la branche maxillaire du nerf trijumeau pour le traitement du syndrome équin de hochement de tête à médiation du trijumeau. Un hongre hanovrien warmblood âgé de 5 ans a été présenté pour un hochement de tête récurrent exacerbé par l'exercice. Le cheval a manifesté des signes cliniques de mouvements verticaux répétitifs de la tête, du frottement de la face sur les jambes avant et sur le sol, des éternuements répétitifs et le frappement du museau avec les jambes avant. Les signes cliniques se sont traduits par un cheval qui ne pouvait pas être monté et était dangereux. Les signes cliniques étaient les plus persistants à la lumière du soleil directe, mais se produisaient lors d'un état d'excitation, de l'exercice ou avec la bride à l'intérieur. Un diagnostic de syndrome de hochement de tête à médiation du trijumeau a été posé. Le traitement chirurgical a été réalisé avec une approche supraorbitale à la branche maxillaire du nerf trijumeau au sortir du foramen rond, où une neurolyse interne (peignage des nerfs) a été effectuée sur les nerfs gauche et droit. Le comportement de hochements sévères de la tête s'est résorbé après la chirurgie. Le cheval a manifesté un frottement de la face du museau qui a commencé 96 heures après la chirurgie et s'est résorbé pendant une période de 12 jours à l'aide d'une thérapie aux corticostéroïdes et à la vitamine E. Le cheval est devenu apte au pâturage et les signes cliniques se sont résorbés en présence de la lumière du soleil, mais les mouvements verticaux répétitifs de la tête ont persisté avec une selle, ce qui a rendu le cheval peu agréable pour la monture.(Traduit par Isabelle Vallières).

Forgiving the self and physical and mental health correlates: a meta-analytic review.

Self-forgiveness has been conceptualized as a coping strategy that may improve health and well-being. To better understand the functions of self-forgiveness, this meta-analysis examines the correlates of self-forgiveness associated with physical and mental health. For physical health, across 18 samples and 5,653 participants, the correlation was .32. For psychological well-being, across 65 samples and 17,939 participants, the correlation was .45. To augment this primary focus on physical and mental health correlates, we estimated the relationships between self-forgiveness and specific mental health constructs and relationship outcomes. Implications for future basic and applied research on self-forgiveness are discussed.

A phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment of postherpetic neuralgia in gabapentin inadequate responders.

OBJECTIVE: To compare the efficacy of high-dose (3,600 mg/day) vs low-dose (1,200 mg/day) oral gabapentin enacarbil (GEn) on pain intensity in adults with postherpetic neuralgia (PHN) and a history of inadequate response to ≥1,800 mg/day gabapentin. DESIGN: Multicenter, randomized, double-blind, crossover study (NCT00617461). SETTING: Thirty-five outpatient centers in Germany and the United States. SUBJECTS: Subjects aged ≥18 years with a diagnosis of PHN. METHODS: During a 2-week baseline period, subjects received open-label treatment with 1,800 mg/day gabapentin. Subjects who had a mean 24-hour average pain intensity score ≥4 during the last 7 days of the baseline period were randomized to receive GEn (1,200 or 3,600 mg/day) for treatment period 1 (28 days), followed by GEn 2,400 mg/day (4 days), and the alternate GEn dose for treatment period 2 (28 days). RESULTS: There was a modest but significant improvement in pain intensity scores with GEn 3,600 mg vs 1,200 mg (adjusted mean [90% confidence interval] treatment difference, -0.29 [-0.48 to -0.10]; P = 0.013). The difference in efficacy between doses was observed primarily in subjects who received the higher dose during treatment period 2; certain aspects of the study design may have contributed to this outcome. Plasma steady-state gabapentin exposure during GEn treatment was as expected and consistent between treatment periods. No new safety signals or adverse event trends relating to GEn exposure were identified. CONCLUSIONS: While the overall results demonstrated efficacy in a PHN population, the differences between treatment periods confound the interpretation. These findings could provide insight into future trial designs.

Ageing, the digital and everyday life during and since the Covid-19 pandemic.

Introduction: During and since the Covid-19 pandemic there has been an intensified integration of digital technologies into the everyday lives of older people. We do, however, know little about the ways in which older people incorporate digital technologies and communications into their daily lives and their own meanings, embodiment and experiences of the digital during and since the Covid-19 pandemic. Method: The aim of our research was to explore the use of digital devices during and since the Covid-19 pandemic and to identify facilitators and barriers to incorporating digital devices into everyday life. The research involved a series of online focus groups with people aged between 63 and 86 years living in the United Kingdom and were conducted in 2022. Each focus group lasted around 90 min and data was audio-recorded and transcribed. The data was analysed thematically. Results: From the analysis, three interconnecting whilst analytically distinct themes around the meaning and experiences of using digital devices in everyday life during and since the pandemic, are thematically presented as: (1) Incorporating the digital into everyday life; (2) Social and digital connectivity; and (3) Challenges and limitations of the digital in everyday life. Discussion: The research has provided insights into the way digital devices were used by older people during and since the Covid-19 pandemic. In particular, we highlight the increasing importance of digital connectivity and the ways in which older people actively engage (and resist) technologies of communication in their daily lives; and the significance of embodied co-presence and the immediacy of shared space and/or time is highlighted.