Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Are children with food allergies more likely to have lower urinary tract symptoms? A case-control study.

INTRODUCTION: There are multiple historic reports linking lower urinary tract symptoms (LUTS) in children with food allergies (FA), but contemporary studies are sparse. The objective of this study was to evaluate a potential link between FA and LUTS in the pediatric population. We hypothesized that children with FAs are more likely to have LUTS. MATERIALS AND METHODS: After local IRB approval, pediatric patients (6-17 years [y]) with FAs proven by positive skin prick and/or serum IgE testing were invited to participate. A control group of pediatric patients without FAs was also recruited. All families/legal guardians signed informed consent, and all children signed written assent. Each participant filled out the Vancouver Symptom Score (VSS), a validated questionnaire for dysfunctional elimination syndrome, and the Pediatric Incontinence Questionnaire (PinQ), a validated quality of life assessment for children with bladder dysfunction. Demographic and clinical information were obtained retrospectively. RESULTS: From 2019-2020, 26 children with FAs and 57 without agreed to participate. Mean age was 9.3 y (IQR 7.9 y-13.5 y). There were no differences in gender, age, or race between the two cohorts. There were no significant differences between the two groups in mean VSS score or mean PinQ score. Four children with FAs (15%) and 15 children without (26%) had VSS score ≥ 11 (p = 0.339), indicating dysfunctional elimination. The median PinQ score was 0 (IQR 0-2) in both cohorts. CONCLUSIONS: This study did not identify an association between FAs and LUTS in a population of pediatric patients with laboratory proven FAs.

Audit of cancer yields after prostate MRI using both the PI-RADS version 2 and Likert scoring systems.

AIM: To audit diagnostic yields of the updated magnetic resonance imaging (MRI)-directed prostate cancer diagnostic service according to Prostate Imaging - Reporting and Data System (PI-RADS) version 2 and Likert assessments, comparing outcomes of the two scoring systems. MATERIALS AND METHODS: Consecutive men with suspected cancer undergoing prostate MRI were included. Biopsy rates and histological diagnostic yields of all and International Society of Urological Pathology Grade Group (ISUP GG) ≥2 cancers according to PI-RADS and Likert assessment categories were documented and outcomes compared. RESULTS: Of 326 men (91% biopsy naive), 177 (54%) underwent transrectal (n=119) or transperineal (n=58) ultrasound-guided biopsies; 92% with negative MRI avoided immediate biopsies following multidisciplinary team (MDT) review. All cancer and ISUP GG ≥ 2 cancer-detection rates increased with increasing suspicion scores. Prospective paired PI-RADS and Likert scoring was undertaken in 323/326 studies, with 87% concordance rate. High concordance between PI-RADS and Likert scores was observed in negative MRI (99%) and score 5 (96%). High discordance was demonstrated in the PI-RADS 4 group (32% with PI-RADS 4 categories up-risked to Likert 5). All cancer and ISUP GG ≥ 2 cancer detection rates for MRI score ≥3 were 78% and 63%, and for MRI score ≥4 were 75% and 61%, respectively for both PI-RADS and Likert scoring systems. CONCLUSIONS: Most men with negative prostate MRI can avoid immediate biopsies following MDT review. Performance of PI-RADS and Likert scoring systems in clinically significant cancer detection after positive MRI is equivalent. Discordance between PI-RADS and Likert systems seems mostly confined to PI-RADS 4 categories.

A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. PATIENTS AND METHODS: PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0-1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. RESULTS: Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9-14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73-1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1-4.2), compared with 3.4 (2.2-4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8-19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74-1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. CONCLUSION: This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.

Diagnostic yields in patients with suspected prostate cancer undergoing MRI as the first-line investigation in routine practice.

AIM: To document cancer yields of magnetic resonance imaging (MRI)-directed biopsies in men with suspected prostate cancer referred to secondary care. MATERIALS AND METHODS: Men with suspected cancer undergoing multiparametric prostate MRI as the first-line investigation were included in the present study. Systematic transrectal prostate biopsies with/without cognitive targeted biopsies were performed. Diagnostic yields of International Society of Urological Pathology (ISUP) ≥2 cancers by the Prostate Imaging Reporting and Data System (PI-RADS) category were recorded. Impacts of prostate-specific antigen (PSA) density on biopsy results and yields of non-targeted biopsies in MRI non-suspicious prostate sextants assessed. RESULTS: Of 262 men (90.5% biopsy naive), 86 (33%) MRI examinations were negative (PI-RADS 1-2) and 176 (67%) positive (PI-RADS 3: 8%; PI-RADS 4: 21%; PI-RADS 5: 38%). Two hundred and thirteen of 262 patients underwent a biopsy. ISUP ≥2 cancer detection rates were 8% (5/61) for PI-RADS 1-2, 18% (3/17) for PI-RADS 3, 49% (22/45) for PI-RADS 4, and 80% (72/90) for PI-RADS 5. Proportions of ISUP ≥2 increased with higher PSA densities in positive patients (%ISUP ≥2 for PSA density groups <0.12, 0.12 to <0.15 and ≥ 0.15 was 0%, 0%, 25% for PI-RADS 3, 21%, 33%, 68% for PI-RADS 4 and 40%, 83%, 89% for PI-RADS 5 respectively). ISUP ≥2 cancers were twice as likely in tumour adjacent sextants (52% versus 24%), without upgrading of gland level histology from insignificant to clinically significant prostate cancer by the sampling of normal-appearing tumour non-adjacent sextants. CONCLUSIONS: One third of men can avoid biopsy after negative MRI. Cancer detection rates increase with PSA density values within positive MRI suspicion categories. Sampling normal-appearing tumour non-adjacent sextants may be unnecessary for whole-gland therapy.

Candidaemia and a risk predictive model for overall mortality: a prospective multicentre study.

BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.

Impact of early palliative care on caregivers of patients with advanced cancer: cluster randomised trial.

Background: Early palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care. Patients and methods: Twenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6-24 months, Eastern Cooperative Oncology Group 0-2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months. Results: A total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P = 0.007) and 4 months (P = 0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4 months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P = 0.87, 4 months: P = 0.60). Conclusion: Early palliative care increased satisfaction with care in caregivers of patients with advanced cancer. ClinicalTrials.gov identifier: NCT01248624.

MRI performed on dedicated knee coils is inaccurate for the measurement of tibial tubercle trochlear groove distance.

OBJECTIVE: Tibial tubercle trochlear groove distance (TTD) is a significant factor in patello-femoral instability. Initially described on CT scans with the knee in full extension, the measurement has been validated on MR scans. Dedicated knee MRI coils have subsequently superseded both CT and MRI body coils for knee imaging. However, the knee rests in partial flexion within the dedicated knee coil. The objective of this study is to investigate whether images from dedicated knee MRI coils produce different TTD measurements from MR body coils. MATERIALS AND METHODS: Thirty-two symptomatic knees (27 patients) had simultaneous knee MR scans performed in both a dedicated knee coil and a body coil. TTD measurements were independently compared to assess whether the coil type used affected TTD. RESULTS: Patients' ages ranged from 10 to 27 years (mean 15 years). Mean TTD in the dedicated knee coil (partially flexed knee) was 11.3 mm compared with 19.9 mm in the body coil (that permits full knee extension). The mean difference was 8.6 mm, which was highly significant (p < 0.0001, unpaired t test). Inter-rater correlation co-efficient was 96 %. Of the knees that recorded a "normal" TTD on the dedicated knee coil, 60-100 % recorded a "pathological" TTD on body coil images, depending on which diagnostic value for "normal" cut-off was used. CONCLUSION: This study has identified a highly significant difference in TTD measurement when knees are scanned in a dedicated knee coil with the knee partially flexed, compared with an MR body coil. It is critical for surgeons and radiologists managing patello-femoral instability to appreciate this profound difference. TTD measurement taken from knees scanned in dedicated knee coils may lead to patients being falsely re-assured or erroneously denied surgery.

Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

Mitogenomic and microsatellite variation in descendants of the founder population of Newfoundland: high genetic diversity in an historically isolated population.

The island of Newfoundland, the first of England's overseas colonies, was settled from the 17th century onward by restricted numbers of English, Irish, and French immigrants, in small "outport" communities that have maintained geographic, religious, and linguistic isolation to the latest generations. To measure the extent of modification and loss of genetic variation through founder effect, drift, and inbreeding in this historically isolated population, we analyzed the complete mitochondrial DNA (mtDNA) genomes and 14 microsatellite loci from each of 27 individuals with matrilineal ancestries extending to the colonial period. Every individual has a unique mtDNA genome sequence. All but one of these genomes are assignable to one of five major (H,J,K,T, and U) or minor (I) European haplogroups. The possibility of homoplasy at single nucleotide polymorphism (SNP) sites that define subtypes within the H haplogroup is discussed. Observed haplogroup proportions do not differ significantly from those of western Europeans or between English and Irish Newfoundlanders. The exceptional individual is a member of haplogroup A2, who appears to be the descendant of a Mi'kmaq First Nations mother and a French father, a common marriage pattern in the early settlement of Newfoundland. Microsatellite diversity is high (HE = 0.763), unstructured with respect to mtDNA haplotype or ethnicity, and there is no evidence of linkage disequilibrium. There is a small but significant degree of inbreeding (FIS = 0.0174). Collection of whole mtDNA genome data was facilitated by the use of microarray sequencing, and we describe a simple algorithm that is 99.67% efficient for sequence recovery.

Treatment of primary nocturnal enuresis in children: a review.

Primary nocturnal enuresis is a common childhood disorder. Treatment approaches bridge the psychological and medical fields. A substantial body of literature addresses the various ways of treating enuresis, from pharmaceuticals to behavioural interventions. The medical and psychological literatures have proceeded relatively independently from one another and there has been little interconnection between the US and international literatures, resulting in a lack of discourse and integration among researchers investigating treatment outcomes for enuresis. This review examined the evidence base for treatments of primary nocturnal enuresis in children. Psychological, pharmaceutical and multi-component interventions are discussed. This review sought to provide an integrated interdisciplinary and international perspective on treatment efficacy for nocturnal enuresis by expressly gathering publications from psychological and medical fields, as well as US and international sources. The literature supported the urine alarm as the most effective intervention for nocturnal enuresis and demonstrated the benefit of combining the urine alarm with other components, both behavioural and pharmaceutical. In particular, recent literature showed that the urine alarm, when used in conjunction with antidiuretic medication (i.e. desmopressin), leads to more dry nights earlier in the conditioning process. Disparities between the different literatures were discussed.

PROState Pathway Embedded Comparative Trial: The IP3-PROSPECT study.

INTRODUCTION: The traditional double blind RCT is the 'gold standard' trial design. For a variety of reasons, these designs often fail to accrue enough participants to conclude. This is particularly challenging in localized prostate cancer. The cohort multiple randomised controlled trial (cmRCT) trial design may represent an alternative approach to delivering robust comparative data in prostate cancer. PATIENTS AND METHODS: IP3-PROSPECT is a cmRCT designed to test multiple prostate cancer interventions from eligible men in one cohort. Key to the design is two points of consent. First, at point of consent one, men referred for prostate cancer investigations are invited to join the cohort. They may then be randomly invited at a later date to consider an intervention at point of consent two. In the pilot phase we will test the acceptability and feasibility of developing the cohort. RESULTS: Acceptability and feasibility of the study will be measured by a combination of quantitative and qualitative methods. The primary outcome measure is the rate of consent to inclusion to the IP3-PROSPECT cohort. Secondary outcome measures include the completeness of data collection at sites and return rates of patient questionnaires. We will also interview patients and healthcare professionals to explore their thoughts on the implementation, practicality and efficiency of IP3-PROSPECT. CONCLUSION: The IP3-PROSPECT study will evaluate the cmRCT design in prostate cancer. Initially we will pilot the design, assessing for acceptability and feasibility. The cmRCT is an innovative design that offers potential for building a modern comparative evidence base for prostate cancer.

Atrial fibrillation and the risk of death in patients with heart failure: a literature-based meta-analysis.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common, associated with significant morbidity and mortality, and frequently coexist. It is uncertain from published data if the presence of AF in patients with HF is associated with an incremental adverse outcome. The aim of this study was to combine the results of all studies investigating prognosis for patients with HF and AF compared with those in sinus rhythm (SR) to asses the mortality risk associated with this arrhythmia. METHODS: Electronic databases were searched (Biological Abstracts, Current Contents, EMBASE, Medline, Medline In-progress, PubMed and Scopus), to 31 December 2006, using the key words congestive heart failure, heart failure, ventricular dysfunction, atrial fibrillation, atrial flutter, sinus rhythm, prognosis, outcome, death and hospitalization. Bibliographies of retrieved publications were hand searched. Studies were eligible if they included a HF population and if outcomes were reported by cardiac rhythm (AF or SR). Studies were reviewed by predetermined protocol (including quality assessment). Data were pooled using a random effects model. RESULTS: Twenty studies were included (from 3380 initially identified) representing 32946 patients (10819 deaths). Nine randomized controlled trials (RCT) were included. The prevalence of AF was 15%, crude mortality rates were 46% (AF) and 33% (SR). The odds ratio for death was 1.33 (95% confidence interval (CI) 1.12-1.59) for AF compared with SR. Eleven observational studies were included. The prevalence of AF was 23%, crude mortality rates were 38% (AF) and 25% (SR). The odds ratio for death was 1.57 (95% CI 1.20-2.05) for AF compared with SR. CONCLUSION: This meta-analysis demonstrates that AF is associated with worse outcomes for patients with HF compared with those with SR. Further research is required to determine whether the adverse outcome associated with AF is related to the arrhythmia itself, or to variables, such as HF severity, patient age and comorbidity.

Critical care triage during the COVID-19 pandemic in South Africa: A constitutional imperative!

Triage and rationing of scarce intensive care unit (ICU) resources are an unavoidable necessity. In routine circumstances, ICU triage is premised on the best interests of an individual patient; however, when increased demand exceeds capacity, as during an infectious disease outbreak, healthcare providers need to make difficult decisions to benefit the broader community while still respecting individual interests. We are currently living through an unprecedented period, with South Africa (SA) facing the challenges of the global COVID-19 pandemic. The Critical Care Society of Southern Africa (CCSSA) expedited the development of a triage guidance document to inform the appropriate and fair use of scarce ICU resources during this pandemic. Triage decision-making is based on the clinical odds of a positive ICU outcome, balanced against the risk of mortality and longer-term morbidity affecting quality of life. Factors such as age and comorbid conditions are considered for their potential impact on clinical outcome, but are never the sole criteria for denying ICU-level care. Arbitrary, unfair discrimination is never condoned. The CCSSA COVID-19 triage guideline is aligned with SA law and international ethical standards, and upholds respect for all persons. The Bill of Rights, however, does not mandate the level of care enshrined in the constitutional right to healthcare. ICU admission is not always appropriate, available or feasible for every person suffering critical illness or injury; however, everyone has the right to receive appropriate healthcare at another level. If ICU resources are used for people who do not stand to benefit, this effectively denies others access to potentially life-saving healthcare. Appropriate triaging can therefore be considered a constitutional imperative.

Privacy rights of human research participants in South Africa must be taken seriously.

Letter by Thaldar and Townsend, following an article by the same authors (Thaldar D, Townsend B. Genomic research and privacy: A response to Staunton et al. S Afr Med J 2020;110(3):172-174. https://doi.org/10.7196/SAMJ.2020.v110i3.14431) and both commenting on an article by Staunton et al. (Staunton C, Adams R, Botes M, et al. Safeguarding the future of genomic research in South Africa: Broad consent and the Protection of Personal Information Act No. 4 of 2013. S Afr Med J 2019;109(7):468-470. https://doi.org/10.7196/SAMJ.2019.v109i7.14148); and response to article and letter by Staunton et al.

TNF-alpha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis.

Although tumor necrosis factor-alpha (TNF-alpha) blockade is a very effective therapy for rheumatoid arthritis (RA), not all patients achieve a favorable outcome. The objective of this study was to determine if the common TNF-alpha variant -308(A) predicts poor response to TNF-alpha inhibitors in RA patients using meta-analysis. Studies were identified using MEDLINE and EMBASE. Data were extracted based on DAS28 or achieving at least American College of Rheumatology 20 response. A total of nine studies met the inclusion criteria representing a total of 692 RA patients. There was no significant heterogeneity among study effect sizes (P=0.36). The frequency of the A allele was 22% (119/531) in responders and 37% (60/161) in non-responders. The odds of having the A allele was lower in responders versus non-responders (odds ratio (OR)=0.43, 95% confidence intervals (CI): 0.28-0.68, P=0.000245), irrespective of the TNF-alpha inhibitor prescribed, indicating that the -308(A) variant predicts poor response to TNF-alpha inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-alpha therapy for RA should now be formally assessed.

Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment.

A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

Selenium: biochemical role as a component of glutathione peroxidase.

When hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H(2)O(2), added glutathione failed to protect the hemoglobin from oxidative damage. This occurred because the erythrocytes were practically devoid of glutathione-peroxidase activity. Extensively purified preparations of glutathione peroxidase contained a large part of the (75)Se of erythrocytes labeled in vivo. Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase.

Acute neurological problems: frequency, consultation patterns and the uses of a rapid access neurology clinic.

In secondary care, some patients with acute neurological symptoms are never seen by a neurologist. Rapid access neurology clinics could provide patients with timely access to neurology services. We analysed a retrospective cohort of 12,024 consecutive patients attending the 'immediate care' area of the emergency department or the acute medical admissions unit of the Royal Infirmary of Edinburgh. A total of 1,036 patients (9%) presented with a neurological complaint, of whom 680 (66%) did not have any contact with neurology services. The most common problems were epileptic seizure, cerebrovascular diseases and headache. Of the patients with epileptic seizure or headache who were not seen by a neurologist, about 40% might have benefited from neurological assessment. Following the introduction of a weekly rapid access neurology clinic, the most common problems seen were headache, symptoms that turned out to be medically unexplained and epileptic seizure.