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Cognitive performance in idiopathic intracranial hypertension and relevance of intracranial pressure.
No full textCognitive impairments have been reported in idiopathic intracranial hypertension; however, evidence supporting these deficits is scarce and contributing factors have not been defined. Using a case-control prospective study, we identified multiple domains of deficiency in a cohort of 66 female adult idiopathic intracranial hypertension patients. We identified significantly impaired attention networks (executive function) and sustained attention compared to a body mass index and age matched control group of 25 healthy female participants. We aimed to investigate how cognitive function changed over time and demonstrated that deficits were not permanent. Participants exhibited improvement in several domains including executive function, sustained attention and verbal short-term memory over 12-month follow-up. Improved cognition over time was associated with reduction in intracranial pressure but not body weight. We then evaluated cognition before and after a lumbar puncture with acute reduction in intracranial pressure and noted significant improvement in sustained attention to response task performance. The impact of comorbidities (headache, depression, adiposity and obstructive sleep apnoea) was also explored. We observed that body mass index and the obesity associated cytokine interleukin-6 (serum and cerebrospinal fluid) were not associated with cognitive performance. Headache severity during cognitive testing, co-morbid depression and markers of obstructive sleep apnoea were adversely associated with cognitive performance. Dysregulation of the cortisol generating enzyme 11β hydroxysteroid dehydrogenase type 1 has been observed in idiopathic intracranial hypertension. Elevated cortisol has been associated with impaired cognition. Here, we utilized liquid chromatography-tandem mass spectrometry for multi-steroid profiling in serum and cerebrospinal fluid in idiopathic intracranial hypertension patients. We noted that reduction in the serum cortisol:cortisone ratio in those undergoing bariatric surgery at 12 months was associated with improving verbal working memory. The clinical relevance of cognitive deficits was noted in their significant association with impaired reliability to perform visual field tests, the cornerstone of monitoring vision in idiopathic intracranial hypertension. Our findings propose that cognitive impairment should be accepted as a clinical manifestation of idiopathic intracranial hypertension and impairs the ability to perform visual field testing reliably. Importantly, cognitive deficits can improve over time and with reduction of intracranial pressure. Treating comorbid depression, obstructive sleep apnoea and headache could improve cognitive performance in idiopathic intracranial hypertension
Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension.
No full textThe 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised. We developed international consensus reporting guidelines for cellular and molecular pathology content in clinical trial protocols (the SPIRIT-Path extension) using an international Delphi process, which assesses candidate items generated from a previous systematic review, followed by an expert consensus meeting. 74 individuals from five continents responded, including clinicians, statisticians, laboratory scientists, patient advocates, funders, industry representatives, journal editors, and regulators. The SPIRIT-Path guidelines recommend 14 additional items (seven extensions to the SPIRIT checklist and seven elaborations) that should be addressed in trial protocols containing pathology content, alongside the SPIRIT 2013 Statement items. SPIRIT-Path recommends that protocols should document the individuals, processes, and standards for all cellular and molecular pathology components of the trial, including all stages of the specimen pathway and any digital pathology methods, with specific consideration of the value of trial data and biological tissues for additional translational studies
An informatics consult approach for generating clinical evidence for treatment decisions.
No full textBACKGROUND
An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.
METHODS
We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.
RESULTS
We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.
CONCLUSION
We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service
Minimally invasive liver resection for huge (≥10 cm) tumors: an international multicenter matched cohort study with regression discontinuity analyses.
No full textBackground
The application and feasibility of minimally invasive liver resection (MILR) for huge liver tumours (≥10 cm) has not been well documented.
Methods
Retrospective analysis of data on 6,617 patients who had MILR for liver tumours were gathered from 21 international centers between 2009-2019. Huge tumors and large tumors were defined as tumors with a size ≥10.0 cm and 3.0-9.9 cm based on histology, respectively. 1:1 coarsened exact-matching (CEM) and 1:2 Mahalanobis distance-matching (MDM) was performed according to clinically-selected variables. Regression discontinuity analyses were performed as an additional line of sensitivity analysis to estimate local treatment effects at the 10-cm tumor size cutoff.
Results
Of 2,890 patients with tumours ≥3 cm, there were 205 huge tumors. After 1:1 CEM, 174 huge tumors were matched to 174 large tumors; and after 1:2 MDM, 190 huge tumours were matched to 380 large tumours. There was significantly and consistently increased intraoperative blood loss, frequency in the application of Pringle maneuver, major morbidity and postoperative stay in the huge tumour group compared to the large tumour group after both 1:1 CEM and 1:2 MDM. These findings were reinforced in RD analyses. Intraoperative blood transfusion rate and open conversion rate were significantly higher in the huge tumor group after only 1:2 MDM but not 1:1 CEM.
Conclusions
MILR for huge tumours can be safely performed in expert centers It is an operation with substantial complexity and high technical requirement, with worse perioperative outcomes compared to MILR for large tumors, therefore judicious patient selection is pivotal
Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.
No full textBackground
Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS.
Methods
REALIST phase 1 was an open label, dose escalation trial in which cohorts of mechanically ventilated patients with moderate to severe ARDS received increasing doses (100, 200 or 400 × 10 cells) of a single intravenous infusion of ORBCEL-C in a 3 + 3 design. The primary safety outcome was the incidence of serious adverse events. Dose limiting toxicity was defined as a serious adverse reaction within seven days. Trial registration clinicaltrials.gov NCT03042143.
Findings
Nine patients were recruited between the 7th January 2019 and 14th January 2020. Study drug administration was well tolerated and no dose limiting toxicity was reported in any of the three cohorts. Eight adverse events were reported for four patients. Pyrexia within 24 h of study drug administration was reported in two patients as pre-specified adverse events. A further two adverse events (non-sustained ventricular tachycardia and deranged liver enzymes), were reported as adverse reactions. Four serious adverse events were reported (colonic perforation, gastric perforation, bradycardia and myocarditis) but none were deemed related to administration of ORBCEL-C. At day 28 no patients had died in cohort one (100 × 10), three patients had died in cohort two (200 × 10) and one patient had died in cohort three (400 × 10). Overall day 28 mortality was 44% ( = 4/9).
Interpretation
A single intravenous infusion of ORBCEL-C was well tolerated in patients with moderate to severe ARDS. No dose limiting toxicity was reported up to 400 × 10 cells
Sexual exposure and sexual behaviour in the interval between gonorrhoea treatment and test of cure: a cross-sectional cohort study.
No full textOBJECTIVES
We explored sexual contact in the interval between the treatment for gonorrhoea and attending for a test of cure (ToC) and identified factors associated with sexual contact in this period.
METHODS
Multivariable analysis of demographic, behavioural and clinical data with self-reported sexual contact prior to attending for a gonorrhoea ToC evaluation among participants recruited into the 'Gentamicin for the Treatment of Gonorrhoea' trial in England, between October 2014 and November 2016. Associations with sexual contact were expressed as prevalence ratios (PR) and their corresponding 95% CI.
RESULTS
The median time to ToC was 15 days (interquartile range 14-20 days). 197/540 (37%) participants reported sexual contact in the time between treatment and ToC. Of these, 173/197 (88%) participants reported inconsistent condom use, including with previous partners (133/197 (68%)). A history of gonorrhoea (adjusted PR (aPR) 1.32 (1.03 to 1.69)) or syphilis (aPR 1.19 (1.08 to 1.32)), being in regular (aPR 1.71 (1.41 to 2.09)) sexual relationships, high number of partners in the last 3 months (aPR 1.77 (1.25 to 2.51))-'more than 5 partners' vs '0 to 1 partner', and attending for a ToC more than 14 days after treatment (aPR 1.40 (1.08 to 1. 81)) were associated with reporting sexual contact before the ToC appointment. However, age (aPR (1.00 (0.99 to 1.01)) and presenting with specific symptoms at baseline (aPR 1.17 (0.95 to 1.44)) were not associated with sexual contact by the ToC attendance.
CONCLUSION
Sexual activity after receiving treatment for gonorrhoea and prior to a ToC evaluation was common. This was associated with previous infection history and specific behavioural characteristics. Knowledge of these factors can help guide safe sex counselling at the time of treatment
Patterns of Nerve Injury and Recovery Rates of Infraclavicular Brachial Plexus Lesions Following Anterior Shoulder Dislocation.
No full textPURPOSE
We reviewed our cases of infraclavicular brachial plexus injuries associated with anterior shoulder dislocation to determine patterns of injury, recovery rates, and factors associated with a poor motor outcome.
METHODS
This was a retrospective review of patients who had sustained a concomitant nerve injury following dislocation of the glenohumeral joint treated with closed manipulation. The data collected included patient demographics, injury factors, and patterns of neurological deficits. The Medical Research Council (MRC) grade for motor power was the primary outcome measure, where a grade of 4 or 5 was regarded as achieving good motor recovery. Univariate and multivariable analyses were used to identify factors associated with persistent motor weakness (MRC grades 0-3) at the final follow-up.
RESULTS
Between 2015 and 2019, 61 patients were assessed. There were 36 males and 25 females, with a median age of 64 years (interquartile range [IQR], 53-73 years). Four patterns of injury were identified: (1) isolated axillary nerve lesions; (2) single cord lesions; (3) combined lesions involving the medial and posterior cords; and (4) diffuse lesions affecting all 3 cords. Of 28 patients with isolated axillary nerve injuries, 22 recovered. All lateral cord injuries (11/11) and 20 of 24 posterior cord injuries recovered spontaneously. Recovery of hand intrinsic function from medial cord injuries had the worst outcome, with 14 of 27 patients not recovering beyond MRC grades 0 to 3. The median duration of dislocation before reduction was 6 hours (IQR, 3-12 hours). A multivariate analysis showed an association between the duration of shoulder dislocation and the likelihood of persistent motor weakness.
CONCLUSIONS
Shoulder dislocations with motor deficits should be regarded as orthopedic emergencies and reduced expediently. Persistent motor weakness may be associated with a prolonged duration of dislocation prior to glenohumeral relocation.
TYPE OF STUDY/LEVEL OF EVIDENCE
Prognostic IV
BSACI Registry for Immunotherapy (BRIT): Providing safe and effective immunotherapy for allergies and urticaria.
No full text
