Mapping interictal discharges using intracranial EEG-fMRI to predict postsurgical outcomes.

Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-fMRI results are more likely to delineate seizure generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions pre-operatively and compared the extent of resection of these areas to post-operative outcome. Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most Clinically Relevant brain activation cluster using available clinical information. The Maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium, or high) based on the difference of the peak z-scores between the Maximum and Second Maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to post-operative outcome. We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the Clinically Relevant cluster) and objective (Maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the Maximum cluster and post-operative outcome. Resection of this area was associated with good post-operative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence Maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0). Objective methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good post-operative outcomes. However, resection of the peak voxel within higher confidence Maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome.

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

OBJECTIVE: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. METHODS: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. RESULTS: Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. SIGNIFICANCE: Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Atypical mycobacterial infections - management and when to treat.

PURPOSE OF REVIEW: Infections caused by nontuberculous mycobacteria (NTM) are increasing for several reasons, including diagnostic advances, increased awareness and a larger at-risk population. NTM pulmonary disease is surpassing tuberculosis (TB) in some low incidence areas. This review summarizes the latest literature and guidelines and aims to be a concise source outlining treatment and management of NTM lung infections, integrating established treatment paradigms with novel pharmacological interventions. RECENT FINDINGS: Recent additions to NTM treatment are inhaled liposomal amikacin and the anti-TB drug bedaquiline. Several other new or repurposed treatments are being explored in vitro, in animal models and in clinical trials, including novel beta-lactamase inhibitor/lactam combinations, dual-lactam combinations, efflux pump inhibitors, novel antimicrobials, inhaled clofazimine suspension and bacteriophages. SUMMARY: Patients with NTM pulmonary disease are mainly female and older with significant delay between diagnosis and treatment being common. Treatment varies according to causative organism, drug susceptibilities, radiological type and disease severity. Underlying chronic conditions, drug intolerances and interactions require careful consideration. In all cases, at least three drugs should be used to minimize acquisition of drug resistance, and all patients should receive a minimum of 12 months of treatment. Expert advice should be taken. NTM treatment is longer than TB treatment, more likely to fail and more likely to cause toxicity. The relatively small numbers of patients affected by each NTM species has limited research. Novel treatments hold promise; nevertheless, it is likely that new solutions for NTM management will stem from the TB pipeline for the foreseeable future.

Refining a model of collaborative care for people with a diagnosis of bipolar, schizophrenia or other psychoses in England: a qualitative formative evaluation.

BACKGROUND: Many people diagnosed with schizophrenia, bipolar or other psychoses in England receive the majority of their healthcare from primary care. Primary care practitioners may not be well equipped to meet their needs and there is often poor communication with secondary care. Collaborative care is a promising alternative model but has not been trialled specifically with this service user group in England. Collaborative care for other mental health conditions has not been widely implemented despite evidence of its effectiveness. We carried out a formative evaluation of the PARTNERS model of collaborative care, with the aim of establishing barriers and facilitators to delivery, identifying implementation support requirements and testing the initial programme theory. METHODS: The PARTNERS intervention was delivered on a small scale in three sites. Qualitative data was collected from primary and secondary care practitioners, service users and family carers, using semi-structured interviews, session recordings and tape-assisted recall. Deductive and inductive thematic analysis was carried out; themes were compared to the programme theory and used to inform an implementation support strategy. RESULTS: Key components of the intervention that were not consistently delivered as intended were: interaction with primary care teams, the use of coaching, and supervision. Barriers and facilitators identified were related to service commitment, care partner skills, supervisor understanding and service user motivation. An implementation support strategy was developed, with researcher facilitation of communication and supervision and additional training for practitioners. Some components of the intervention were not experienced as intended; this appeared to reflect difficulties with operationalising the intervention. Analysis of data relating to the intended outcomes of the intervention indicated that the mechanisms proposed in the programme theory had operated as expected. CONCLUSIONS: Additional implementation support is likely to be required for the PARTNERS model to be delivered; the effectiveness of such support may be affected by practitioner and service user readiness to change. There is also a need to test the programme theory more fully. These issues will be addressed in the process evaluation of our full trial. TRIAL REGISTRATION: ISRCTN95702682 , 26 October 2017.

Engaging "seldom heard" groups in research and intervention development: Offender mental health.

BACKGROUND: People subject to the criminal justice system often have substantially different life-experiences from the general population. Patient and public involvement (PPI) of "seldom heard" groups provides valuable experiential knowledge, enhancing research. OBJECTIVE: To share our jointly developed techniques to ensure the meaningful engagement and contribution of people with lived experience of the criminal justice system (PWLECJS) in research, trial science, intervention theory development and dissemination. METHODS: Commitment to adequate financial resources, appropriate staff skills and adequate time were combined with previous learning. PWLECJS were approached through local community organizations. A group was established and met fortnightly for ten months in an unthreatening environment and had a rolling membership. Ongoing engagement was promoted by the group taking responsibility for the rules, interactive and accessible activities, feeding back tangible impacts, ongoing contact, building a work ethic, joint celebrations, sessions with individual academic researchers and pro-actively managed endings. RESULTS: The Peer Researchers contributed to study documents, training academic researchers, research data collection and analysis, intervention delivery and theory development and trial science. The Peer Researchers gained in confidence and an improved sense of self-worth. The Academic Researchers gained skills, knowledge and an increased openness to being challenged. DISCUSSION AND CONCLUSIONS: PWLECJS can be meaningful included in health research and intervention development. The key elements required are listed. Challenges included differences in priorities for timescales and dissemination, resource limitations and the use of Peer Researchers' names. Further research is required to understand what might be of relevance for other "seldom heard" groups.

Analgesic effects of methadone and magnesium following posterior spinal fusion for idiopathic scoliosis in adolescents: a randomized controlled trial.

PURPOSE: To provide optimal conditions for neurophysiological monitoring and rapid awakening, remifentanil is commonly used during pediatric spinal surgery. However, remifentanil may induce hyperalgesia and increase postoperative opioid requirements. We evaluated the potential of methadone or magnesium to prevent remifentanil-induced hyperalgesia. METHODS: Using a prospective, randomized, blinded design, adolescents presenting for posterior spinal fusion to treat idiopathic scoliosis were assigned to receive desflurane with remifentanil alone (REMI), remifentanil + methadone (MET) (0.1 mg/kg IV over 15 min), or remifentanil + magnesium (MAG) (50 mg/kg bolus over 30 min followed by 10 mg/kg/h). Primary outcomes were opioid requirements and postoperative pain scores. Secondary outcomes included intraoperative anesthetic requirements, neurophysiological monitoring conditions, and emergence times. RESULTS: Data analysis included 60 patients. Total opioid requirement (hydromorphone) in the REMI group (received perioperatively and on the inpatient ward) was 0.34 ± 0.11 mg/kg compared to 0.26 ± 0.10 mg/kg in the MET group (95% confidence interval (CI) of difference: - 0.14, - 0.01; p = 0.035). The difference in opioid requirements between the REMI and MET group was related to intraoperative dosing (0.04 ± 0.02 mg/kg vs. 0.02 ± 0.01 mg/kg; 95% CI of difference: - 0.01, - 0.02; p = 0.003). No difference was noted in pain scores, and no differences were noted when comparing the REMI and MAG groups. CONCLUSION: With the dosing regimens in the current study, the only benefit noted with methadone was a decrease in perioperative opioid requirements. However, given the potential for hyperalgesia with the intraoperative use of remifentanil, adjunctive use of methadone appears warranted.

Microbiological Profile of Fracture Related Infection at a UK Major Trauma Centre.

Fracture Related Infection (FRI) represents one of the biggest challenges for Trauma and Orthopaedic surgery. A better understanding of the microbiological profile should assist with decision-making and optimising outcomes. Our primary aim was to report on the microbiological profile of FRI cases treated over a six-year period at one of Europe's busiest trauma centres. Secondarily, we sought to correlate our findings with existing anti-microbiological protocols and report on diagnostic techniques employed in our practice. All adult cases of FRI treated in our institution between 2016 and 2021 were identified, retrospectively. We recorded patient demographics, diagnostic strategies, causative organisms and antibiotic susceptibilities. There were 330 infection episodes in 294 patients. A total of 463 potentially pathogenic organisms (78 different species) were identified from cultures, of which 57.2% were gram-positive and 39.7% gram-negative. Polymicrobial cultures were found in 33.6% of cases and no causative organism was found in 17.5%. The most prevalent organisms were Staphylococcus aureus (24.4%), coagulase-negative Staphylococci (14%), Pseudomonas aeruginosa (8.2%), Enterobacter species (7.8%) and Escherichia coli (6.9%). Resistant gram-positive organisms (methicillin resistant Staphylococcus aureus or vancomycin-resistant Enterococci) were implicated in 3.3% of infection episodes and resistant gram-negatives (extended-spectrum beta-lactamase, ampC or carbapenemase-producing bacteria) in 13.6%. The organisms cultured in 96.3% of infection episodes would have been covered by our empirical systemic antibiotic choice of teicoplanin and meropenem. To our knowledge, this is the largest reported single-centre cohort of FRIs from a major trauma centre. Our results demonstrate patterns in microbiological profiles that should serve to inform the decision-making process regarding antibiotic choices for both prophylaxis and treatment.

Outcome assessment in neuromuscular spinal deformity.

Patient-based outcome measures are important tools quantifying the disease-specific and/or global quality of life (QOL) effects of spinal deformity treatment. In patients with neuromuscular disorders such as cerebral palsy, muscular dystrophy, and myelomeningocele, treatment effects must be differentiated from underlying disease functional impairments. In general, the goals of spinal surgery in these patients are to improve QOL by enhancing sitting balance and posture, improving lung and gastrointestinal function, and reducing pain and deformity. In selected patients, improving ambulation and hand function may also be realistic surgical goals. QOL measures specific to both the neuromuscular diagnosis and spinal deformity provide higher quality information on treatment outcomes for a particular patient than standard radiographic measures. This article reviews patient-based outcome measures in spinal deformity patients with neuromuscular disorders, including their development and use in comparative outcome studies in the recent literature.

A group-based behavioural intervention for weight management (PROGROUP) versus usual care in adults with severe obesity: a feasibility randomised controlled trial protocol.

BACKGROUND: Approximately 15 million people in the UK live with obesity, around 5 million of whom have severe obesity (body mass index (BMI) ≥35kg/m2). Having severe obesity markedly compromises health, well-being and quality of life, and substantially reduces life expectancy. These adverse outcomes are prevented or ameliorated by weight loss, for which sustained behavioural change is the cornerstone of treatment. Although NHS specialist 'Tier 3' Weight Management Services (T3WMS) support people with severe obesity, using individual and group-based treatment, the current evidence on optimal intervention design and outcomes is limited. Due to heterogeneity of severe obesity, there is a need to tailor treatment to address individual needs. Despite this heterogeneity, there are good reasons to suspect that a structured group-based behavioural intervention may be more effective and cost-effective for the treatment of severe obesity compared to usual care. The aims of this study are to test the feasibility of establishing and delivering a multi-centre randomised controlled clinical trial to compare a group-based behavioural intervention versus usual care in people with severe obesity. METHODS: This feasibility randomised controlled study is a partially clustered multi-centre trial of PROGROUP (a novel group-based behavioural intervention) versus usual care. Adults ≥18 years of age who have been newly referred to and accepted by NHS T3WMS will be eligible if they have a BMI ≥40, or ≥35 kg/m2 with comorbidity, are suitable for group-based care and are willing to be randomised. Exclusion criteria are participation in another weight management study, planned bariatric surgery during the trial, and unwillingness or inability to attend group sessions. Outcome assessors will be blinded to treatment allocation and success of blinding will be evaluated. Clinical measures will be collected at baseline, 6 and 12 months post-randomisation. Secondary outcome measures will be self-reported and collected remotely. Process and economic evaluations will be conducted. DISCUSSION: This randomised feasibility study has been designed to test all the required research procedures and additionally explore three key issues; the feasibility of implementing a complex trial at participating NHS T3WMS, training the multidisciplinary healthcare teams in a standard intervention, and the acceptability of a group intervention for these particularly complex patients. TRIAL REGISTRATION: ISRCTN number 22088800.

Boosting exercise beliefs and motivation through a psychological intervention designed for poststroke populations.

BACKGROUND: The effect of patient education on reducing stroke has had mixed effects, raising questions about how to achieve optimal benefit. Because past evaluations have typically lacked an appropriate theoretical base, the design of past research may have missed important effects. METHOD: This study used a social cognitive framework to identify variables that might change in response to education. A mixed design was used to evaluate 2 approaches to an intervention, both of which included education. Twenty-six seniors completed a measure of stroke knowledge and beliefs twice: before and after an intervention that was either "standard" (educational brochure plus activities that were not about stroke) or "enhanced" (educational brochure plus activities designed to enhance beliefs about stroke). Outcome measures were health beliefs, intention to exercise to reduce stroke, and stroke knowledge. RESULTS: Selected beliefs changed significantly over time but not differentially across conditions. Beliefs that changed were (1) perceived susceptibility to stroke, and (2) perceived benefit of exercise to reduce risk. Benefit beliefs, in particular, were strongly and positively associated with intention to exercise. CONCLUSION: Findings suggest that basic approaches to patient education may influence health beliefs. More effective stroke prevention programs may result from continued consideration of the role of health beliefs in such programs.

Evaluation of a primary care-based collaborative care model (PARTNERS2) for people with diagnoses of schizophrenia, bipolar, or other psychoses: study protocol for a cluster randomised controlled trial.

BACKGROUND: Current NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. AIM: The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. DESIGN & SETTING: This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). METHOD: PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. CONCLUSION: The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses.

Outcome analysis of surgery for Blount disease.

BACKGROUND: The purpose of this study was to evaluate the results of surgery for Blount disease using a patient-derived outcome assessment. Our hypothesis was that an outcome score that quantitates the patient's level of satisfaction should correlate with specific ranges of correction for those radiologic variables traditionally used to evaluate Blount disease. The surgeon's aim should be to realign abnormal preoperative geometry to achieve those ranges that have a significant correlation with good outcome. METHODS: Medical records from 2 hospitals (Barbados and Trinidad) were reviewed and patients who had surgery for Blount's from 1997 to 2005 were identified and recalled. Responders completed a Blount's Outcome Questionnaire, were examined clinically, and standing radiographs were taken. The questionnaire was designed by modifying the AAOS Pediatrics-Parent/Child Outcome Instrument. Linear regression was used to assess the predictive effect of selected radiographic measures on a visual analog pain score and satisfaction score calculated from the questionnaire. The model was adjusted for confounders: country, age at the time of study, sex, body mass index, and years postsurgery. Variables in the adjusted model achieving significance at P<0.05 were included in a multiple regression analysis. RESULTS: Fifty knees in 41 patients were included. The median satisfaction score was 93%. The metaphyseal-diaphyseal angle (MDA) and anatomical femoral-tibial angle (aFTA), both had a quadratic effect on the pain score (P<0.001). The predicted pain score was minimized at the MDA range of 0 to -10 degrees and at the aFTA range of 0 to +5 degrees. A significant effect on the satisfaction score was noted for MDA (P=0.02) and aFTA (P<0.001) with scores maximized at the MDA range of +5 to -5 degrees and at positive aFTA (valgus angulation). For women the satisfaction scores were lower and the pain scores higher. Overweight patients had higher pain scores. CONCLUSIONS: Results of this evaluation of the association between patient outcome scores (for pain and satisfaction) and postoperative clinical and radiologic variables support the recommendation that surgical correction should aim at producing an MDA score between -5 and +5 degrees and a valgus alignment with an aFTA score of 0 to 5 degrees. LEVEL OF EVIDENCE: Therapeutic study, investigating the results of treatment. Level III.

Management of foot and ankle injuries in pediatric and adolescent athletes: a narrative review.

In this review, we focus on the treatment of injuries to the foot and ankle in the adolescent athlete. While many injuries in the adolescent foot and ankle are similar to or overlap with their counterparts in the adult population, the anatomy of the adolescent ankle, especially the presence of growth plates, results in different injury patterns in many cases and calls for specific management approaches. We discuss the unique anatomy of the pediatric patient as well as the diagnostic evaluation and treatment of common injuries in the young athlete.