Prevalence and Predictors of Hereditary Hemorrhagic Telangiectasia and Capillary-Malformation Arteriovenous Malformation Syndrome Among Children with Neurovascular Malformations.

OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

COVID-19 vaccine allergy advice and guidance: The experience of a UK tertiary referral centre.

Objective: The objective was to review COVID-19 vaccine allergy advice and guidance requests received and assess the impact of advice outcome on vaccination outcome. Design: A retrospective analysis of requests for advice and guidance regarding COVID-19 vaccine allergy was completed using an electronic referral system from February 2021 to January 2022. Participants: A total of 1265 independent patient requests for advice were received from primary care. Full vaccination information was available on 1210 patients who were included in the analysis. Main outcome measures: We evaluated the specific outcome of request for advice (written advice versus allergy consultation), rate of vaccination, vaccination combinations, and tolerance of vaccination. Results: Of the 1210 patients included, 959 (79%) were female. Eight hundred and ninety-six (74%) requests were managed with written advice only and of these 675 (75%) patients went on to be vaccinated. Overall, 891 (74%) of the population were vaccinated with 2 or more doses.Two hundred and nineteen patient consultations were undertaken with 109 (50%) prior to the first vaccination. Forty-nine (45%) consultations prior to vaccination were undertaken due to a label of anaphylaxis to vaccination in the past. Vaccination was recommended for all patients, and 78 (72%) of these received a first dose. Eight of these patients (10%) had symptoms within 1 h of vaccine administration.One hundred and ten (50%) consultations were undertaken for adverse reactions post COVID-19 vaccination, with 84 (76%) concerning immediate symptoms. Thirty patients (27%) who had a consultation had had adrenaline administered post vaccination. One patient had biopsy confirmed Stevens Johnson Syndrome and was referred to Dermatology. All others due for further doses (107 patients) were recommended to have subsequent doses with 49 (45%) offered the same vaccine. Eighty-nine patients had a vaccine administered post adverse reaction and 79 (88%) tolerated the dose.Skin testing and challenge to polyethylene glycol were negative in the 8 patients tested. Conclusions: Over 1000 requests for advice and guidance were received during the review period, managed mainly with written advice. The overwhelming majority of requests for advice and consultations were for females, with equal distribution both pre- and post-COVID-19 vaccine administration. Vaccination was recommended in all but 1 patient (with biopsy confirmed Stevens Johnson Syndrome). Polyethylene glycol allergy was not confirmed in any patient, nor did any patient have confirmed anaphylaxis when the vaccine was administered under our supervision, suggesting that type 1 mediated hypersensitivity is uncommon even in this "high risk" population.

Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.

OBJECTIVES: To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case. DESIGN: Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths. SETTING: SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making. PARTICIPANTS: Publicly available data on patients with COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time. RESULTS: SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7). CONCLUSIONS: The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.

How to investigate a suspected immune deficiency in adults.

Patients with immune deficiencies can present with variable clinical phenotypes. This often translates into a significant delay in their diagnosis, and resultant patient morbidity. This review summarises the most common types of immunodeficiency disorders, primary and secondary, along with their key features. It provides a structured approach for the clinician on when to suspect an immunodeficiency, the initial investigations pathway and when a specialist referral should be considered.

One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi.

In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).

Shared decision making by United Kingdom osteopathic students: an observational study using the OPTION-12 instrument.

Background: At the crux of patient centred care is Shared Decision Making (SDM), which benefits patient and practitioner. Despite external pressures, studies indicate that SDM remains poorly practised across a variety of healthcare professions. The degree of SDM engagement within United Kingdom osteopathic undergraduate teaching clinics is currently unknown. Methods: In 2014 we used the reliable and validated OPTION-12 (O12) instrument to calculate a score that reflected the degree of SDM utility in one United Kingdom Osteopathic Educational Institute's teaching clinic. We also aimed to compare these scores with those previously obtained for physiotherapists working within the United Kingdom's National Health Service. Student-patient initial and follow-up encounters were audio recorded, transcribed and scored using the O12. Comparisons between the following O12 scores were performed: the Osteopathic Educational Institute's 4th and 3rd year students; the Osteopathic Educational Institute's student's initial and follow-up patient encounters; the Osteopathic Educational Institute's students and National Health Service physiotherapists. Results: We analysed 35.5 h of transcribed data from 30 student-patient encounters (7 initial: 23 follow-up). An O12 score of 0.6% (range 0-10.4%) was calculated. No significant differences were found between year groups or encounter types. Significant differences were found compared to National Health Service physiotherapist (score = 24.4%): (U = 144, z = 4.25, p < 0.0005); although both scores are below the 60% threshold for competent SDM behaviour. Conclusions: Undergraduate osteopaths did not appear to engage in competent SDM behaviours, implying traditional and paternalistic styles of decision making that align with results from other manual therapy professions. Students in this study did not practise competent SDM behaviours. Effective educational strategies are required to ensure SDM behaviours reach competent levels.

Neglecting the neglected: the objective evidence of underfunding in rheumatic heart disease.

BACKGROUND: Despite the substantial global burden of disease, rheumatic heart disease research receives little funding globally. METHODS: Using data from the Global Burden of Disease Study and funding from the G-FINDER database, we propose a novel logarithmic disability neglect index (DNI) to describe disease burden using disability-adjusted life years relative to funding for 16 major tropical diseases. RESULTS: Across a range of diseases, rheumatic heart disease received the least funding relative to disease burden (DNI=3.83). Other diseases facing similar underfunding include cysticercosis (DNI=2.71) and soil-transmitted helminths (DNI=2.41). CONCLUSIONS: Rheumatic heart disease remains severely underfunded relative to disease burden.

Immunoglobulin replacement for secondary immunodeficiency after B-cell targeted therapies in autoimmune rheumatic disease: Systematic literature review.

BACKGROUND: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease. OBJECTIVES: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD). METHODS: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor. We limited the search to English language papers with abstracts published over the last 10 years. Abstracts were screened for original data regarding hypogammaglobulinemia following BCTT and the use of IGRT for hypogammaglobulinemia following BCTT. We also searched current recommendations from national/international organisations including British Society for Rheumatology, UK Department of Health, American College of Rheumatology, and American Academy of Asthma, Allergy and Immunology. RESULTS: 222 abstracts were identified. Eight papers had original relevant data that met our search criteria. These studies were largely retrospective cohort studies with small patient numbers receiving IGRT. The literature highlights the induction of a sustained antibody deficiency, risk factors for hypogammaglobulinemia after BCTT including low baseline serum IgG levels, how to monitor patients for the development of hypogammaglobulinemia and the limited evidence available on intervention thresholds for commencing IGRT. CONCLUSION: The benefit of BCTT needs to be balanced against the risk of inducing a sustained secondary antibody deficiency. Consensus guidelines would be useful to enable appropriate assessment prior to and following BCTT in preventing and diagnosing hypogammaglobulinemia. Definitions for symptomatic hypogammaglobulinemia, intervention thresholds and treatment targets for IGRT, and its cost-effectiveness are required.

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases.

OBJECTIVES: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. METHODS: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. RESULTS: Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82-100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. CONCLUSION: These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.

Transabdominal ultrasound: Can it be used to detect and quantify adhesions/reported pain, following Caesarean section?

BACKGROUND: Caesarean section is common in the UK with post-procedural adhesions causing life-long clinical symptoms and impacting future pregnancies. This study's aim was to explore associations between these surgical adhesions, via transabdominal ultrasound findings, and perceived symptoms. METHOD: Females demonstrating 1-3 transverse, lower-segment Caesareans were included. Visceral slide transabdominal ultrasound elicited positive adhesions (<1 cm movement) and negative adhesions (>1 cm movement). Scar tissue quality was assessed by the Patient and Observer Scar Assessment Scale (POSAS) and Numerical rating scales (NRS) described pain symptoms. The relationship between adhesions was explored using Fisher's exact test and multiple regression analysis. RESULTS: Twenty-two subjects (mean-age 35) were recruited; twenty participants (91%) had undergone 1 Caesarean, one each of the remainder had undergone 2 and 3 Caesareans respectively. Increased Visceral slide (>1 cm) was seen as predictive of increased scar pain (R2 = 0.76 (95% CI 0.12-0.28), P < 0.001). CONCLUSION: Caesarean adhesion scans showed significant associations with pain symptomology. Comprehensive adhesion assessment needs to be developed to improve long term outcomes of adhesions. Transabdominal Ultrasound can be considered a useful, quick and non-deleterious alternative diagnostic tool to Laparoscopy, therefore preventing further adhesion formation.

The treatment of a pregnant HIV positive patient with cryptococcal meningitis in Malawi. Case report and review of treatment options.

This case reports cryptococcal meningitis in an HIV positive woman on antiretroviral therapy, presenting with left middle cerebral artery stroke at 30 weeks gestation. The patient had well-controlled HIV (CD4 count over 200 cells/mL). The immunosuppressive effects of the pregnancy likely contributed to the development of cryptococcal disease. The patient was successfully treated with two weeks of amphotericin B followed by fluconazole, delivered a healthy baby, but remained with a permanent severe neurological deficit.

Inclusion and exclusion criteria used in non-specific low back pain trials: a review of randomised controlled trials published between 2006 and 2012.

BACKGROUND: Low back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP. METHODS: A systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category. RESULTS: We included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds (n = 8, 5%), while low back pain (n = 150, 89%) with or without referred leg pain (n = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery (n = 84, 50%), pregnancy (n = 81, 48%), malignancy (n = 78, 46%), trauma (n = 63, 37%) and psychological conditions (n = 58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise (n = 44, 26%), neurological signs (n = 34, 20%) or disc herniation (n = 30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis (n = 35, 21%), spinal stenosis (n = 31, 18%) or osteoporosis (n = 27, 16%). CONCLUSION: RCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

Patients Using an Online Forum for Reporting Progress When Engaging With a Six-Week Exercise Program for Knee Conditioning: Feasibility Study.

BACKGROUND: The use of electronic health (eHealth) and Web-based resources for patients with knee pain is expanding. Padlet is an online noticeboard that can facilitate patient interaction by posting virtual "sticky notes." OBJECTIVE: The primary aim of this study was to determine feasibility of patients in a 6-week knee exercise program using Padlet as an online forum for self-reporting on outcome progression. METHODS: Undergraduate manual therapy students were recruited as part of a 6-week study into knee conditioning. Participants were encouraged to post maximum effort readings from quadriceps and gluteal home exercises captured from standard bathroom scales on a bespoke Padlet. Experience and progression reporting were encouraged. Posted data were analyzed for association between engagement, entry frequency, and participant characteristics. Individual data facilitated single-subject, multiple-baseline analysis using statistical process control. Experiential narrative was analyzed thematically. RESULTS: Nineteen participants were recruited (47%, 9/19 female); ages ranged from 19 to 53 years. Twelve individuals (63%) opted to engage with the forum (range 4-40 entries), with five (42%) reporting across all 6 weeks. Gender did not influence reporting (odds ratio [OR] 0.76, 95% CI 0.06-6.93). No significant difference manifested between body mass index and engagement P=.46); age and entry frequency did not correlate (R2=.054, 95% CI ­0.42 to 0.51, P=.83). Statistically significant conditioning profiles arose in single participants. Themes of pain, mitigation, and response were inducted from the experiences posted. CONCLUSIONS: Patients will engage with an online forum for reporting progress when undertaking exercise programs. In contrast to related literature, no significant association was found with reporting and gender, age, or body mass index. Individual posted data allowed multiple-baseline analysis and experiential induction from participants. Conditioning responses were evident on visual inspection. The importance of individualized visual data to patients and the role of forums in monitoring patients' progress in symptomatic knee pain populations need further consideration.

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).

What Is the Proportion of Studies Reporting Patient and Practitioner Satisfaction with Software Support Tools Used in the Management of Knee Pain and Is This Related to Sample Size, Effect Size, and Journal Impact Factor?

INTRODUCTION: E-health software tools have been deployed in managing knee conditions. Reporting of patient and practitioner satisfaction in studies regarding e-health usage is not widely explored. The objective of this review was to identify studies describing patient and practitioner satisfaction with software use concerning knee pain. MATERIALS AND METHODS: A computerized search was undertaken: four electronic databases were searched from January 2007 until January 2017. Keywords were decision dashboard, clinical decision, Web-based resource, evidence support, and knee. Full texts were scanned for effect of size reporting and satisfaction scales from participants and practitioners. Binary regression was run; impact factor and sample size were predictors with indicators for satisfaction and effect size reporting as dependent variables. RESULTS: Seventy-seven articles were retrieved; 37 studies were included in final analysis. Ten studies reported patient satisfaction ratings (27.8%): a single study reported both patient and practitioner satisfaction (2.8%). Randomized control trials were the most common design (35%) and knee osteoarthritis the most prevalent condition (38%). Electronic patient-reported outcome measures and Web-based training were the most common interventions. No significant dependency was found within the regression models (p > 0.05). DISCUSSION AND CONCLUSIONS: The proportion of reporting of patient satisfaction was low; practitioner satisfaction was poorly represented. There may be implications for the suitability of administering e-health, a medium for capturing further meta-evidence needs to be established and used as best practice for implicated studies in future. This is the first review of its kind to address patient and practitioner satisfaction with knee e-health.