Reliability of salivary cortisol and testosterone to a high-intensity cycling protocol to highlight overtraining.

Athletes physically overload to improve performance. Unbalanced stress/recovery may induce overtraining, which is difficult to diagnosis as no diagnostic marker exists. Hormonal responses to a 55/80 cycle (30-min of alternating blocks of 1-min at 55% and 4-min at 80% maximum work rate) may highlight early-stage overtraining (overreaching), as blunted cortisol and testosterone responses to 55/80 follows intensified training. However, the reliability of hormonal responses to 55/80 when not overreached is unknown. Therefore, reported blunted hormonal responses could be due to inconsistent cortisol and testosterone responses to 55/80. Participants (n = 23) completed three 55/80 bouts, >7 days apart, with no exercise 24 h pre-trials. Pre-exercise urine osmolality and stress questionnaire responses were measured. Pre, post, and 30-min post-exercise saliva samples were collected for cortisol and testosterone assessment. Salivary cortisol and testosterone responses, osmolality and well-being were not different between trials. Salivary cortisol and testosterone elevated from pre- to post-exercise [by 4.2 nmol.L-1 (cortisol) and 307 pmol.L-1 (testosterone)], and 30 min post-exercise [by 160 pmol.L-1 (testosterone) only]. Intraclass correlation coefficients for pre to peak post-exercise cortisol (0.89; good) and testosterone (0.53; moderate) were calculated. This demonstrates that 55/80 induces reliable elevations of salivary cortisol and testosterone when in a healthy state.

Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival.

Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012-2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)-based treatment. Patients were categorised based on clinician's treatment choice into 'palliative' (n = 52), 'less intensive: MTX ± rituximab ± alkylators' (n = 74) and 'intensive: MTX/cytarabine combinations' (n = 118) groups. Complete remission (CR) rate, two-year progression-free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment-related mortality (TRM) was 6·8% for MTX-treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5-21) over a median of three cycles. Higher relative dose intensity of MTX (MTX-RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two-year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX-based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX-RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

Superficial vein thrombosis: a current approach to management.

Superficial vein thrombosis (SVT) was considered to be a benign and self-limiting condition. However, it is now appreciated that a significant proportion of those presenting with SVT will have concomitant deep vein thrombosis or pulmonary embolism, or are at significant risk of developing deep venous thromboembolism. Potential therapeutic options include topical preparations, compression therapy (stockings, bandages), medication such as non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants (therapeutic or prophylactic doses) and surgery, ligation or stripping, of superficial veins. The treatment of choice is therapeutic/intermediate dose low molecular weight heparin or prophylactic dose fondaparinux administered for 4-6 weeks. The cost-effectiveness of treatment is a concern and more targeted therapy is required.

Patients' perceptions of self-administered dosing to opioid agonist treatment and other changes during the COVID-19 pandemic: a qualitative study.

OBJECTIVES: During the COVID-19 pandemic, addiction treatment services received official guidance asking them to limit face-to-face contact with patients and to prescribe opioid agonist treatment (OAT) medication flexibly. With the aim for most patients to receive take-home supplies for self-administration rather than attendance for observed daily dosing. DESIGN: This was a theory-driven, clinically applied qualitative study, with data for thematic analysis collected by semi-structured, audio-recorded, telephone interviews. PARTICIPANTS: Twenty-seven adults (aged ≥18 years) enrolled in sublingual (tablet) buprenorphine and oral (liquid) methadone OAT. SETTING: Community addictions centre in the London Borough of Lambeth operated by South London and Maudsley NHS Trust. RESULTS: Three major themes were identified: (1) dissatisfaction and perceived stigma with OAT medication dispensing arrangements before the pandemic; (2) positive adaptations in response to COVID-19 by services; (3) participants recommended that, according to preference and evidence of adherence, OAT should be personalised to offer increasing medication supplies for self-administration from as early as 7 days after commencement of maintenance prescribing. CONCLUSIONS: In an applied qualitative study of patients enrolled in OAT during the COVID-19 pandemic, participants endorsed their opportunity to take medication themselves at home and with virtual addiction support. Most patients described a preference for self-administration with increased dispensing supplies, from as early as 7 days into maintenance treatment, if they could demonstrate adherence to their prescription.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63.

Systematic review and meta-analysis of oral paracetamol versus combination oral analgesics for acute musculoskeletal injuries.

OBJECTIVE: The aim of this systematic review and meta-analysis was to determine if a combination of analgesics conveys any significant clinical benefit over paracetamol alone in managing acute musculoskeletal injuries. METHODS: Two reviewers independently searched MEDLINE (via PubMed), EMBASE and Cochrane electronic databases. Randomised controlled trials comparing paracetamol with paracetamol plus other oral analgesics in managing acute musculoskeletal injuries (e.g. sprains, contusions) were identified. Outcomes were reduction in pain score, adverse events and need for additional analgesia. Studies were critiqued using the Cochrane Risk of Bias Assessment Tool and data analysed using RevMAN meta-analysis software. RESULTS: Six studies were included (n = 1254). No paediatric studies were identified. Five studies compared paracetamol to paracetamol plus NSAID. One study also included an opioid in the combination group. There was no clinically important difference between groups for reduction in pain score in the first 2 h, 24 h or 72 h. At 2 h the mean difference in reduction in pain score at rest on 100 mm VAS was 0.72 mm (-1.36, 2.79), P = 0.5. On activity it was -1.79 mm (-4.08, 0.49), P = 0.12. The risk of adverse events in ED was -0.00 (-0.04, 0.03). More patients receiving combination therapy required additional analgesia in the first 2 h: -0.03 (-0.06, -0.01), P = 0.01. CONCLUSION: Paracetamol monotherapy is a reasonable first-line analgesic for acute musculoskeletal injuries as combining additional oral agents does not result in any significant additional analgesic effect.

Pathophysiology of coronary artery disease: the case for multiparametric imaging.

Interventions to treat coronary artery disease are available but they must be targeted at the correct individuals (and indeed lesions), in order to gain maximal benefit with the minimal adverse effects. Coronary contrast angiography is not able to provide all the information required for the assessment of the effects of artery disease. Other imaging modalities are of growing importance as they can reduce radiation exposure and invasiveness of screening, as well as providing important extra information. The ideal 'multiparametric' imaging technique would assess anatomy, viability and lesion activity in a single quick scan. Currently, MRI is the technology closest to achieving this ideal, although the existing technology still has some limitations. This review discusses the currently available techniques for the imaging of coronary anatomy and of myocardial viability, and considers their benefits and limitations. We also discuss the developing field of imaging molecularly targeted to active coronary lesions. Finally we provide a 5-year view of the current and likely future optimal imaging strategies.