Levelling the playing field through the London Network of the UK clinical trials accelerator platform.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

The influence of primary language on postoperative stroke outcomes.

BACKGROUND: Language barriers have the potential to influence acute stroke outcomes. Thus, we examined postoperative stroke outcomes among non-English primary language speakers. METHODS: Utilizing the Healthcare Cost and Utilization Project State Inpatient Database (2016-2019), we conducted a retrospective cohort study of adults diagnosed with a postoperative stroke in Michigan, Maryland, and New Jersey. Patients were classified by primary language spoken: English (EPL) or non-English (n-EPL). The primary outcome was hospital length-of-stay. Secondary outcomes included stroke intervention, feeding tube, tracheostomy, mortality, cost, disposition, and readmission. Propensity-score matching and post-match regression were used to quantify outcomes. RESULTS: Among 3078 postoperative stroke patients, 6.2 â€‹% were n-EPL. There were no differences in length-of-stay or secondary outcomes, except for higher odds of feeding tube placement (OR 1.95, 95 â€‹% CI 1.10-3.47, p â€‹= â€‹0.0227) in n-EPL. CONCLUSIONS: Postoperative stroke outcomes were comparable by primary language spoken. However, higher odds of feeding tube placement in n-EPL may suggest differences in patient-provider communication.

Post-discharge Mental Healthcare and Emergency General Surgery Readmission for Patients with Serious Mental Illness.

OBJECTIVE: To determine the association between post-discharge mental healthcare and odds of readmission after emergency general surgery (EGS) hospitalization for patients with serious mental illness (SMI). BACKGROUND DATA: A mental health visit (MHV) after medical hospitalization is associated with decreased readmissions for patients with SMI. The impact of a MHV after surgical hospitalization is unknown. METHODS: Using Medicare claims, we performed a retrospective cohort study of hospitalized EGS patients with SMI aged >65.5 (2016-2018). EGS included colorectal, general abdominal, hepatopancreatobiliary, hernia, intestinal obstruction, resuscitation, and upper gastrointestinal conditions. SMI was defined as schizophrenia spectrum, mood, or anxiety disorders. The exposure was MHV within 30 days of discharge. The primary outcome was 30-day readmission. Secondary outcomes included emergency department presentation and psychiatric admission. Inverse probability weighting was used to evaluated outcomes. RESULTS: Of 88,092 analyzed patients, 11,755 (13.3%) had a MHV within 30 days of discharge. 23,696 (26.9%) of patients were managed operatively, 64,395 (73.1%) non-operatively. After adjustment for potential confounders, patients with a post-discharge MHV had lower odds of acute care readmission than patients without a MHV in both operative (OR 0.60; 95% CI: [0.40-0.90]) and non-operative (OR 0.67; 95% CI [0.53-0.84]) cohorts. There was no association between post-discharge MHV and ED presentation or psychiatric admission in the operative or non-operative groups. CONCLUSIONS: Post-discharge MHV after EGS hospitalization was associated with decreased odds of readmission for patients with SMI managed operatively and nonoperatively. In older EGS patients with SMI, coordination of MHVs may be a mechanism to reduce readmission disparities.

Brachial Gunshot Wounds: Injury Patterns and Considerations for Managing the Abnormal Neurological Examination.

BACKGROUND: Nerve injuries from gunshot wounds (GSWs) to the upper arm can cause significant morbidity and loss of function. However, indications for surgical exploration and nerve reconstruction remain unclear as both low- and high-grade injuries can present with an abnormal neurological examination. METHODS: Adult patients presenting with a history of isolated GSW to the upper arm between 2010 and 2019 at a single urban level 1 trauma center were screened for inclusion in this retrospective study. Patient demographics, neurological examination findings, concurrent injuries, and intraoperative findings were gathered. Bivariate analysis was performed to characterize factors associated with nerve injuries. RESULTS: There were 139 adult patients with isolated brachial GSWs, and 49 patients (35%) presented with an abnormal neurological examination and significantly associated with concurrent humerus fractures (39% vs 21%, P = .026) and brachial artery injuries (31% vs 2%, P < .001). Thirty of these 49 patients were operatively explored. Fifteen patients were found to have observed nerve injuries during operative exploration including 8 patients with nerve transections. The radial nerve was the most commonly transected nerve (6), and among the 16 contused nerves, the median (8) was most common. CONCLUSION: Nerve injury from upper arm GSWs is common with directly traumatized nerves confirmed in at least 39% and nerve transection in at least 16% of patients with an abnormal neurological examination. Timely referral to a hand and/or peripheral nerve surgeon for close clinical follow-up, appropriate diagnosis, and any necessary surgical reconstruction with nerve grafts, tendon transfers, and nerve transfers is recommended.

Replay of incidentally encoded episodic memories in the rat.

Although events are not always known to be important when they occur, people can remember details about such incidentally encoded information using episodic memory. Importantly, when information is explicitly encoded for use in an expected test of retention (as in most assessments in animals), it is possible that it is used to generate a planned action1,2,3; thus, the remembered action can occur without remembering the earlier episode. By contrast, when a test is unexpected, transforming information into an action plan is unlikely because the importance of the information and the nature of the test are not yet known. Thus, accurate performance in an unexpected test after incidental encoding documents episodic memory.1,2,3,4,5,6,7,8 Here, we present evidence that rats replay episodic memories of incidentally encoded information in an unexpected assessment of memory. In one task,9 rats reported the third-last item in an explicitly encoded list of trial-unique odors. In a second task,10 rats foraged in a radial maze in the absence of odors. On a critical test, rats foraged in the radial maze, but scented lids covered the food. Next, memory of the third-last odor was assessed. All participating rats correctly answered the unexpected question. These results suggest that rats encoded multiple pieces of putatively unimportant information, and later they replayed a stream of episodic memories when that information was needed to solve an unexpected problem. We propose that rats replay episodic memories of incidentally encoded information, which documents a critical aspect of human episodic memory in a non-human animal.

Barriers and Facilitators to Clinical Practice Development in Men and Women Surgeons.

Importance: Many early-career surgeons struggle to develop their clinical practices, leading to high rates of burnout and attrition. Furthermore, women in surgery receive fewer, less complex, and less remunerative referrals compared with men. An enhanced understanding of the social and structural barriers to optimal growth and equity in clinical practice development is fundamental to guiding interventions to support academic surgeons. Objective: To identify the barriers and facilitators to clinical practice development with attention to differences related to surgeon gender. Design, Setting, and Participants: A multi-institutional qualitative descriptive study was performed using semistructured interviews analyzed with a grounded theory approach. Interviews were conducted at 5 academic medical centers in the US between July 12, 2022, and January 31, 2023. Surgeons with at least 1 year of independent practice experience were selected using purposeful sampling to obtain a representative sample by gender, specialty, academic rank, and years of experience. Main Outcomes and Measures: Surgeon perspectives on external barriers and facilitators of clinical practice development and strategies to support practice development for new academic surgeons. Results: A total of 45 surgeons were interviewed (23 women [51%], 18 with ≤5 years of experience [40%], and 20 with ≥10 years of experience [44%]). Surgeons reported barriers and facilitators related to their colleagues, department, institution, and environment. Dominant themes for both genders were related to competition, case distribution among partners, resource allocation, and geographic market saturation. Women surgeons reported additional challenges related to gender-based discrimination (exclusion, questioning of expertise, role misidentification, salary disparities, and unequal resource allocation) and additional demands (related to appearance, self-advocacy, and nonoperative patient care). Gender concordance with patients and referring physicians was a facilitator of practice development for women. Surgeons suggested several strategies for their colleagues, department, and institution to improve practice development by amplifying facilitators and promoting objectivity and transparency in resource allocation and referrals. Conclusions and Relevance: The findings of this qualitative study suggest that a surgeon's external context has a substantial influence on their practice development. Academic institutions and departments of surgery may consider the influence of their structures and policies on early career surgeons to accelerate practice development and workplace equity.

Ambulatory surgical management of most displaced tibial tubercle fractures in children is safe and efficient.

Purpose: The purpose of this study is to compare the outcome of patients with displaced tibial tubercle fractures treated surgically who spent one or more nights in the hospital after surgery with that of patients treated in an ambulatory setting with no perioperative hospitalization. We hypothesized that tibial tubercle fractures have a low rate of complications and that most patients do well without an overnight hospital stay for observation. Methods: We retrospectively reviewed all pediatric tibial tubercle fractures treated operatively by a single surgeon over a 13.5-year period. Fractures treated in an inpatient setting, defined as at least one night of overnight hospitalization postoperatively, were compared with fractures treated in an ambulatory setting with no perioperative hospitalization. Results: Seventy-one fractures in 70 patients were analyzed. All fractures were treated with open reduction and internal fixation with unicortical screws. Thirty-five fractures (49.3%) were fixed in an ambulatory setting, while 36 (50.7%) were inpatient. There were no significant differences between inpatient demographics (age, gender, body mass index, fracture type). Average operative time was significantly longer in the inpatient group compared with the ambulatory group (97.8 min versus 58.8 min, p < 0.001). There was no significant difference in the incidence of complications between inpatient and ambulatory groups (25.0% versus 11.4%, p = 0.22). No cases of compartment syndrome were noted. Conclusion: Ambulatory surgical treatment of select tibial tubercle fractures with same-day discharge is safe and efficient. Not all patients with surgically treated tibial tubercle fractures need to stay overnight in the hospital.

The Social Contagion Potential of Pro-Vaccine Messages on Black Twitter.

Black Americans in the US not only suffered from disproportionately high hospitalization and death rates throughout the pandemic but also from the consequences of low COVID-19 vaccination rates. This pattern of disparity is linked to distrust of public health systems that originates from a history of medical atrocities committed against Black people. For that reason, mitigation of race-based inequity in COVID-19 impacts might find more success in grassroots information contagion than official public health campaigns. While Black Twitter is well-positioned as a conduit for such information contagion, little is known about message characteristics that would afford it. Here, we tested the impact of four different message frames (personalization, interactive, fear appeal, neutral) on the social contagion potential of bi-modal social media messages promoting COVID-19 vaccinations and finding personalized messages to be the most shareable. Wary of recommending personalization as the blueprint for setting a social contagion health campaign in motion, we probed further to understand the influence of individual-level variables on the communicability of personalized messages. Subsequently, regression models and focus group data were consulted, revealing that thinking styles, vaccine confidence levels, and attitudes toward social media were significant factors of influence on the contagion potential of personalized messages. We discussed the implications of these results for health campaigns.

Technical considerations for replantation: from bony fixation to soft tissue coverage.

Digital replantation is a challenging and at-time tedious operation, but if approached thoughtfully and with reasonable expectations can be a reliable and rewarding undertaking. This article summarizes technical considerations for digital replantations involving flexor tendon zone II. The article has been ordered according to the recommended sequence of a structure-by-structure repair in a non-thumb digit. Special considerations are described for thumb, multiple digits, and heterotopic replantation.

Barriers and facilitators to surgical access in underinsured and immigrant populations.

BACKGROUND: Marginalized communities are at risk of receiving inequitable access to surgical care. We aimed to examine the barriers and facilitators to access to surgery in underinsured and immigrant populations. METHODS: A systematic review of disparities in access to surgical care was performed between January 1, 2000-March 2, 2022. Methodological quality was assessed with the Mixed Methods Appraisal Tool. A convergent integrated approach was used to code common themes between studies. RESULTS: Of 1315 publications, a total of 66 studies were included for systematic review. Eight studies specifically discussed immigrant patient populations. Barriers and facilitators to surgical access were categorized by patient and health systems related factors. CONCLUSIONS: Established facilitators to improve surgical access are centered on patient-level factors while interventions to address systems-related barriers are limited and may be an area for further investigation. Research focused on access to surgery in immigrant populations remains sparse.

Mechanism matters: A 10-year experience of ballistic injuries of the upper extremity.

INTRODUCTION: Upper Extremity gunshot wounds represent a significant strain on community and hospital resources, and reports of their epidemiology are varied. We hypothesized that demographic and socioeconomic variables would be associated with variable injury patterns and management, and that two distinct populations would be affected by upper extremity ballistic injury based on violent versus accidental, self-inflicted mechanism. MATERIALS & METHODS: Retrospective review of all adult patients sustaining ballistic injury to the upper extremity at a single urban Level I trauma center over 10 years (n = 797). Demographic, injury pattern, treatment, and outcomes data were collected. Comparisons between groups were conducted with unpaired t-tests and chi-square testing where appropriate. RESULTS: Most patients were male (89.1%) and mean age was 30.1 years (18-83). Violence accounted for 89.1% of injuries. Black individuals were disproportionately affected at 87% of patients. Shoulder injuries were most common (34%), and wrist least common (7%). Demographics and injury pattern varied significantly between patients sustaining violent injury and those with self-inflicted mechanisms. Patients sustaining violent injury were most often young, Black men more likely to be injured proximally, whereas patients with self-inflicted injuries were more likely to be older, Caucasian men with more comorbidities injured distally. Cumulatively, 35.3% of patients required operative intervention. Distal injuries were more likely operative. The most commonly injured structure across all levels was bone (53%), and 54.3% of fractures required operation. Median follow-up was 24.5 months. Complication rate was 13.6%. CONCLUSIONS: Gunshot wounds of the upper extremity create complex patterns of injury which vary based on level of injury and mechanism. Violent and self-inflicted injuries occur in dissimilar populations and result in distinctive injury patterns.

Effect of Serious Mental Illness on Surgical Consultation and Operative Management of Older Adults with Acute Biliary Disease: A Nationwide Study.

BACKGROUND: Mental illness is associated with worse outcomes after emergency general surgery. To understand how preoperative processes of care may influence disparate outcomes, we examined rates of surgical consultation, treatment, and operative approach between older adults with and without serious mental illness (SMI). STUDY DESIGN: We performed a nationwide, retrospective cohort study of Medicare beneficiaries aged 65.5 years or more hospitalized via the emergency department for acute cholecystitis or biliary colic. SMI was defined as schizophrenia spectrum, mood, and/or anxiety disorders. The primary outcome was surgical consultation. Secondary outcomes included operative treatment and surgical approach (laparoscopic vs open). Multivariable logistic regression was used to examine outcomes with adjustment for potential confounders related to patient demographics, comorbidities, and rates of imaging. RESULTS: Of 85,943 included older adults, 19,549 (22.7%) had SMI. Before adjustment, patients with SMI had lower rates of surgical consultation (78.6% vs 80.2%, p < 0.001) and operative treatment (68.2% vs 71.7%, p < 0.001), but no significant difference regarding laparoscopic approach (92.0% vs 92.1%, p = 0.805). In multivariable regression models with adjustment for confounders, there was no difference in odds of receiving a surgical consultation (odds ratio 0.98 [95% CI 0.93 to 1.03]) or undergoing operative treatment (odds ratio 0.98 [95% CI 0.93 to 1.03]) for patients with SMI compared with those without SMI. CONCLUSIONS: Older adults with SMI had similar odds of receiving surgical consultation and operative treatment as those without SMI. As such, differences in processes of care that result in SMI-related disparities likely occur before or after the point of surgical consultation in this universally insured patient population.

Antibiotic Prophylaxis and Infectious Complications in Isolated Gunshot Wounds to the Upper Extremity.

BACKGROUND: Prophylactic antibiotics are variably prescribed after isolated upper extremity gunshot wounds (UE GSWs). The risk of infection and factors influencing prescribing practice remain poorly understood, and clinical practice guidelines are lacking. METHODS: Adults with isolated UE GSWs over a 10-year period were included. Medical records were reviewed for demographic and injury variables, comorbidities, surgical treatments, antibiotic administration, infectious complications, and follow-up duration. Infection rate was calculated. Bivariate and multivariable linear regression analyses were used to identify patient-related and injury-related factors predictive of prophylactic antibiotic prescription. RESULTS: A total of 281 patients were eligible for inclusion. Prophylactic antibiotics were prescribed at discharge for 111 patients (40%). Multivariable analysis revealed that patients with more distal injuries and ballistic fractures were significantly more likely to receive prophylactic antibiotics. Of patients with at least 30-day postinjury follow-up, 6% developed infections. CONCLUSION: Prophylactic antibiotic administration after UE GSWs was inconsistent but more common in patients with ballistic fractures and injuries in the hand. The overall incidence of infection was found to lie between 3% and 6%. The rate of infection in the antibiotic prophylaxis (2%-6%) group was similar to that in the no-antibiotic (5%-7%) group, suggesting that antibiotic prophylaxis may not have a large impact on infectious risk. However, because this study is nonrandomized, and because this study is underpowered for multivariable modeling of infectious risk, it remains possible that subgroups of this population may still benefit from antibiotic prophylaxis.

Intracranial hemangioma-associated cranial nerve VII palsy treated with propranolol in an infant with possible PHACE syndrome.

A 2-week-old infant with a large vascular birthmark involving her right face presented with right-sided facial paralysis. MRI of the brain revealed multiple intracranial hemangiomas, and the hemangioma within the right temporal bone impinged on the facial nerve, which resulted in paralysis. Cranial nerve palsies are a rare neurological manifestation of PHACE syndrome. We report successful treatment of the facial nerve palsy with oral propranolol.

Childhood lymphomatoid papulosis Type D, a rare and challenging diagnosis.

A 10-year-old female with a several-year history of pityriasis lichenoides (PL) presented with a new, asymptomatic, large, and necrotic ulcer of her right upper arm. Skin biopsy was consistent with lymphomatoid papulosis (LyP) Type D, a recently recognized subtype of LyP that is distinguished histologically by marked epidermotropism and a perivascular infiltrate of medium-sized pleomorphic lymphocytes with a cytotoxic phenotype (CD3+, CD8+). This is only the sixth reported case of LyP Type D in a child, and while the prognosis in children appears favorable, with no reports of progression to lymphoma to date, more experience in children with longer-term follow-up is needed. Our case highlights both the challenging clinical diagnosis, since in our patient the longstanding clinical presentation was indistinguishable from PL, as well as histopathologic diagnosis, which required expert opinion and consensus.

Weight status and meeting the physical activity, sleep, and screen-time guidelines among Texas children: results from a population based, cross-sectional analysis.

BACKGROUND: Evidence suggests that the interactive effects of physical activity, screen-time and sleep are stronger than independent effects of these behaviors on pediatric obesity. However, this hypothesis has not been fully examined among samples of young school-aged children. The aim of this study is to determine the association of weight status with meeting the physical activity, screen-time, and sleep guidelines, independently and concurrently, among 2nd grade children. METHODS: The Texas School Physical Activity and Nutrition Project collected parent-reported physical activity, screen-time, and sleep, and measured body height and weight on a statewide representative weighted sample (n = 320,005) of children. Weighted multivariable logistic regressions were used to assess associations of weight status (classified using age- and sex-specific body weight [kg]/height [m]2, based on International Obesity Task Force cutoffs) with meeting the physical activity, screen-time, and sleep guidelines, while controlling for relevant covariates (age, sex, race/ethnicity, comorbidities etc.). RESULTS: A greater proportion of healthy weight children (9.9%) met the physical activity, screen-time, and sleep guidelines concurrently compared to children who are thin (3.3%), or children with overweight (5.7%), obese (3.5%), and morbid obesity (1.0%). Children who were thin (adjusted odds ratio [aOR]:0.40, 95% confidence interval [CI]: 0.10, 1.50), overweight (aOR = 0.75, CI: 0.33, 1.70), obese (aOR = 0.53, CI: 0.15, 1.81), and morbidly obese (aOR = 0.10, CI: 0.02, 0.28) had lower odds of concurrently meeting the guidelines compared to children with healthy weight. CONCLUSIONS: Among this representative sample of Texas children, weight status was associated with meeting physical activity, screen-time, and sleep guidelines. Future studies should aim to evaluate causal relations between these behaviors and weight status.

The East of England dental trauma service.

BACKGROUND: Current evidence suggests traumatic dental injuries can be difficult to manage in primary care due to uncommon occurrence and challenging patient presentations. Such factors may contribute to general dental practitioners lacking experience and confidence in the assessment, treatment and management of traumatic dental injuries. Furthermore, there are anecdotal accounts of patients presenting to accident and emergency (A&E) services with a traumatic dental injury, which could be placing avoidable strain on secondary care services. For these reasons, a novel primary care-led dental trauma service has been established in the East of England. METHODS: This brief report shares our experiences of establishing this dental trauma service, titled 'Think T's'. It aims to provide effective trauma care across an entire region by a dedicated team of experienced clinicians from primary care settings to reduce inappropriate attendance to secondary care services and upskill colleagues in dental traumatology. FINDINGS AND CONCLUSIONS: Since its inception, the dental trauma service has been public-facing and has managed referrals from a range of sources which include general medical practitioners, A&E clinicians and ambulance services. The service has been well received and has been seeking to integrate with the Directory of Services as well as NHS 111.

Tofacitinib-Associated Cerebral Venous Sinus Thrombosis.

Tofacitinib is a Janus kinase inhibitor indicated to treat adult patients with moderately to severely active ulcerative colitis (UC). Although thrombosis is a known adverse event of tofacitinib, there are no reports specific to cerebral venous sinus thrombosis (CVST). We present a report of a patient presenting with a CVST several months after starting tofacitinib. Initially, this 60-year-old man with poorly controlled UC who previously had a nonthrombotic hemorrhage was found to have venous sinus thromboses of the right transverse and sigmoid sinuses. Hematological workup did not reveal any underlying hypercoagulable conditions, aside from UC. This is the first report of a patient with CVST likely resulting from the Janus kinase inhibitor tofacitinib. This case report should prompt compilation of all thrombotic events in patients receiving tofacitinib.

Neurotoxicity studies with a tropomyosin-related kinase A inhibitor, ASP7962, on the sympathetic and sensory nervous systems in rats.

ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study.