Investigation into the effect of hyperbaric hyperoxia on serum cardiac Troponin T levels as a biomarker of cardiac injury.

Introduction: There is clinical equipoise as to whether hyperoxia is injurious to the myocardium, both in the setting of acute ischaemic insults and on the stable myocardium. This study examined the effect of extreme hyperoxia - in the form of hyperbaric oxygen treatment - on the myocardium through measurement of high-sensitivity cardiac troponin. Methods: Forty-eight individuals were enrolled to undergo a series of 30 exposures to hyperbaric oxygen for treatment of non-cardiac pathologies. High-sensitivity troponin T was measured before and after each session. Results: There was no clinically significant difference in troponin measurements following acute or recurrent sequential exposures to extreme hyperoxia, despite the studied patient population having a high rate of previous ischaemic heart disease or cardiovascular risk factors. Conclusions: This study demonstrates that profound hyperoxaemia does not induce any measurable cardiac injury at a biochemical level. Neither is there a reduction in cardiac troponin to suggest a cardioprotective effect of hyperbaric hyperoxia. This provides some reassurance as to the cardiac safety of the routine use of hyperbaric oxygen treatment in management of non-cardiac pathology.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Evidence-based management approaches for patients with severe chronic obstructive pulmonary disease (COPD): A practice review.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) face limited treatment options and inadequate access to palliative care. AIM: To provide a pragmatic overview of clinical guidelines and produce evidence-based recommendations for severe COPD. Interventions for which there is inconsistent evidence to support their use and areas requiring further research were identified. DESIGN: Practice review of guidelines supported by scoping review methodology to examine the evidence reporting the use of guideline-recommended interventions. DATA SOURCES: An electronic search was undertaken in MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Database of Systematic Reviews, complemented by web searching for guidelines and publications providing primary evidence (July 2021). Guidelines published within the last 5 years and evidence in the last 10 years were included. RESULTS: Severe COPD should be managed using a multidisciplinary approach with a holistic assessment. For stable patients, long-acting beta-agonist/long-acting muscarinic antagonist and pulmonary rehabilitation are recommended. Low dose opioids, self-management, handheld fan and nutritional support may provide small benefits, whereas routine corticosteroids should be avoided. For COPD exacerbations, systematic corticosteroids, non-invasive ventilation and exacerbation action plans are recommended. Short-acting inhaled beta-agonists and antibiotics may be considered but pulmonary rehabilitation should be avoided during hospitalisation. Long term oxygen therapy is only recommended for patients with chronic severe hypoxaemia. Short-acting anticholinergic inhalers, nebulised opioids, oral theophylline or telehealth are not recommended. CONCLUSIONS: Recommended interventions by guidelines are not always supported by high-quality evidence. Further research is required on efficacy and safety of inhaled corticosteroids, antidepressants, benzodiazepines, mucolytics, relaxation and breathing exercises.

Conceptualising effective symptom management in palliative care: a novel model derived from qualitative data.

BACKGROUND: Pain, breathlessness and fatigue are some of the most challenging symptoms to manage in patients with advanced disease. Specialist palliative care leads to better symptom management, but factors contributing to successful symptom management in this context have not been explored. Our aim was to understand what facilitates effective symptom management in specialist palliative care within UK hospices and investigate what barriers are experienced. METHODS: This was a grounded theory study using qualitative semi-structured focus groups and interviews. Participants were recruited from multidisciplinary specialist palliative care teams (doctors, nurses, healthcare assistants, physiotherapists, occupational therapists, complementary therapists, social workers and chaplains) working in inpatient, outpatient and community services provided by five hospices in the United Kingdom. RESULTS: We present a novel qualitative data-derived model of effective symptom management in specialist palliative care. We describe a co-ordinated, multi-faceted, sequential approach involving a process of engagement, partnership, decision-making, and delivery. Interventions to manage symptoms are less effective in psychologically distressed patients. Our data highlights that families of patients have a key role in determining effectiveness of symptom management interventions A holistic approach by a co-ordinated, multi-disciplinary team, including support to recognise and minimise psychological distress might facilitate more effective symptom management. Barriers to symptom management include team discordance and lack of understanding about symptom management by patient and families. CONCLUSIONS: Shared decision-making between patients and professionals and co-ordination of care by a multi-disciplinary team are key components of effective symptom management. Actions to address psychological distress and evaluate the understanding and expectations of patients and their families would enable more effective symptom management. A more effective multi-disciplinary approach would be facilitated by discussion within teams about role competencies and boundaries.

Practice review: Evidence-based and effective management of fatigue in patients with advanced cancer.

BACKGROUND: Fatigue affects most patients living with advanced cancer and is a symptom that healthcare professionals can find difficult to manage. AIM: To provide healthcare professionals with a pragmatic overview of approaches to management of fatigue in patients with advanced cancer that are commonly recommended by guidelines and to evaluate evidence underpinning them. DESIGN: Scoping review methodology was used to determine the strength of evidence supporting use of interventions recommended in management of fatigue in patients with advanced cancer. DATA SOURCES: National or international guidelines were examined if they described the management of fatigue in adult cancer patients and were written within the last 6 years (2015-2021) in English. The Cochrane Database of Systematic Reviews (January 2011-December 2021) was searched for 'cancer' AND 'fatigue' in title, abstract or keywords. A PubMed search was also made. RESULTS: Evidence indicates physical exercise interventions are effective and patients may benefit from energy conservation tactics. Evidence does not support use of psychostimulants such as methylphenidate. Limited data were found on efficacy of corticosteroids, psychological interventions, nutritional intervention, sleep optimization or complementary therapies for management of fatigue in advanced cancer. CONCLUSION: We recommend regular assessment, review and acknowledgement of the impact of fatigue. Exercise and energy conservation should be considered. Pharmacological interventions are not endorsed as a routine approach. Many interventions currently recommended by guidelines are not supported by a robust evidence base and further research on their efficacy is required.

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Adjunctive hyperbaric oxygen treatment for necrotising soft-tissue infections: A systematic review and meta-analysis.

INTRODUCTION: Surgical intervention, broad-spectrum antibiotics and intensive care support are the standard of care in the treatment of necrotising soft-tissue infections (NSTI). Hyperbaric oxygen treatment (HBOT) may be a useful adjunctive treatment and has been used for almost 60 years, but its efficacy remains unknown and has not been systematically appraised. The aim was to systematically review and synthesise the highest level of clinical evidence available to support or refute the use of HBOT in the treatment of NSTI. METHODS: The review was prospectively registered (PROSPERO; CRD42020148706). MEDLINE, EMBASE, CENTRAL and CINAHL were searched for eligible studies that reported outcomes in both HBOT treated and non-HBOT treated individuals with NSTI. In-hospital mortality was the primary outcome. Odds ratio (ORs) were pooled using random-effects models. RESULTS: The search identified 486 papers of which 31 were included in the qualitative synthesis and 21 in the meta-analyses. Meta-analysis on 48,744 patients with NSTI (1,237 (2.5%) HBOT versus 47,507 (97.5%) non-HBOT) showed in-hospital mortality was 4,770 of 48,744 patients overall (9.8%) and the pooled OR was 0.44 (95% CI 0.33-0.58) in favour of HBOT. For major amputation the pooled OR was 0.60 (95% CI 0.28-1.28) in favour of HBOT. The dose of oxygen in these studies was incompletely reported. CONCLUSIONS: Meta-analysis of the non-random comparative data indicates patients with NSTI treated with HBOT have reduced odds of dying during the sentinel event and may be less likely to require a major amputation. The most effective dose of oxygen remains unclear.

Hyperbaric oxygen for sudden hearing loss: Influence of international guidelines on practice in Australia and New Zealand.

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSHL) is an otolaryngologic emergency. The Undersea and Hyperbaric Medicine Society (UHMS) revised practice guidelines in 2014 adding ISSHL to approved indications. This study investigated whether the UHMS guidelines influenced referral and practice in Australia and New Zealand. METHODS: Retrospective review of 319 patient referrals in two time periods (five years prior to addition of ISSHL to indications (T-PRE) and three years post (T-POST)). RESULTS: Seven of eight participating hyperbaric facilities provided data down to the level of the indication for HBOT for analysis. In T-PRE 136 patients were treated with HBOT for ISSHL, representing between 0% and 18% of the total cases to each facility. In the T-POST period 183 patients were treated for ISSHL, representing from 0.35% to 24.8% of the total patients in each facility. Comparison between the two periods shows the proportion of patients treated with ISSHL among all indications increased from 3.2% to 12.1% (P < 0.0009). One facility accounted for 74% (101/136) of ISSHL patients receiving HBOT in T-PRE and 63% (116/183) in T-POST. ISSHL case load at that facility increased from 18% to 24.8% (P = 0.009) after the UHMS guideline publication. Three of the seven units had a significant increase in referrals after the guideline change. CONCLUSION: There remains equipoise regarding HBOT in the management of ISSHL. Only three out of seven units had a significant increase in ISSHL patients after the UHMS guidelines publication. Without well controlled RCTs to develop guidelines based on good evidence this is unlikely to change and practice variation will continue.

An observational trial to establish the effect of hyperbaric oxygen treatment on pelvic late radiation tissue injury due to radiotherapy.

INTRODUCTION: Rates of pelvic cancer are growing globally with around half of these patients receiving radiotherapy. In a small proportion, radiotherapy results in significant late radiation tissue injury (LRTI) to surrounding tissue, most commonly affecting the bladder and bowel mucosa. We conducted a combined prospective and retrospective observational trial to establish the effectiveness of hyperbaric oxygen treatment (HBOT) in improving the symptoms and signs of LRTI in these patients. METHODS: Fifty-two patients were included after receiving radiotherapy for cancers of the bowel, bladder, cervix, prostate or vulva. They received HBOT at 203-243 kPa (2.0-2.4 atmospheres absolute (atm abs)) for 90 minutes with the median number of treatments being 30 (IQR 1). Late effects normal tissues - subjective, objective, management, analytic (LENT-SOMA) scores were recorded before and after treatment. RESULTS: The mean LENT-SOMA scores before and after HBOT were 11.7 (SD 5.3) and 8.1 (5.1) respectively. This reduction in score of 3.7 (95% CI 2.6 to 4.8) was statistically significant (P < 0.001). For radiation cystitis the mean reduction was 3.7 (95% CI 2.4 to 5.0, P < 0.001) and for radiation proctitis was 3.8 (95% CI 1.4 to 6.1, P = 0.004). There were no significant adverse effects recorded. CONCLUSIONS: Hyperbaric oxygen treatment may be an effective and safe treatment for pelvic late tissue radiation injury.

Can preventive hyperbaric oxygen therapy optimise surgical outcome?: A systematic review of randomised controlled trials.

BACKGROUND: A primary underlying cause of postoperative complications is related to the surgical stress response, which may be mitigated by hyperbaric oxygen therapy (HBOT), the intermittent administration of oxygen at a pressure higher than the atmospheric pressure at sea level. Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications. Notwithstanding, the effectiveness (if any) of HBOT across a range of procedures and postoperative outcomes has yet to be clearly quantified. OBJECTIVE: This systematic review aimed to summarise the existing literature on peri-operative HBOT to investigate its potential to optimise surgical patient outcome. DESIGN: A systematic review of randomised controlled trials (RCTs) with narrative summary of results. DATA SOURCES: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were searched without language restrictions through to 19 June 2018. ELIGIBILITY CRITERIA: Studies were included if they involved patients of any age undergoing any surgical procedure and provided with at least one HBOT session in the peri-operative period. Two independent reviewers screened the initial identified trials and determined those to be included. Risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. RESULTS: The search retrieved 775 references, of which 13 RCTs were included (627 patients). Ten RCTs (546 patients) reported treatment was effective for improving at least one of the patient outcomes assessed, while two studies (55 patients) did not find any benefit and one study (26 patients) found a negative effect. A wide range of patient outcomes were reported, and several other methodological limitations were observed among the included studies, such as limited use of sham comparator and lack of blinding. CONCLUSION: Peri-operative preventive HBOT may be a promising intervention to improve surgical patient outcome. However, future work should consider addressing the methodological weaknesses identified in this review. TRIAL REGISTRATION: The protocol (CRD42018102737) was registered with the International ProspectiveRegister of Systematic Reviews (PROSPERO).

Transcutaneous electrical nerve stimulation for advanced cancer pain inpatients in specialist palliative care-a blinded, randomized, sham-controlled pilot cross-over trial.

PURPOSE: Transcutaneous electrical nerve stimulation (TENS) is a treatment option for cancer pain, but the evidence is inconclusive. We aimed to evaluate the efficacy and safety of TENS. METHODS: A blinded, randomized, sham-controlled pilot cross-over trial (NCT02655289) was conducted on an inpatient specialist palliative care ward. We included adult inpatients with cancer pain ≥ 3 on an 11-point numerical rating scale (NRS). Intensity-modulated high TENS (IMT) was compared with placebo TENS (PBT). Patients used both modes according to their preferred application scheme during 24 h with a 24-h washout phase. The primary outcome was change in average pain intensity on the NRS during the preceding 24 h. Responders were patients with at least a "slight improvement." RESULTS: Of 632 patients screened, 25 were randomized (sequence IMT-PBT = 13 and PBT-IMT = 12). Finally, 11 patients in IMT-PBT and 9 in PBT-IMT completed the study (N = 20). The primary outcome did not differ between groups (IMT minus PBT: - 0.2, 95% confidence interval - 0.9 to 0.6). However, responder rates were higher in IMT (17/20 [85%] vs. 10/20 [50%], p = 0.0428). Two patients experienced an uncomfortable feeling caused by the current, one after IMT and one after PBT. Seven patients (35%) desired a TENS prescription. Women and patients with incident pain were most likely to benefit from TENS. CONCLUSION: TENS was safe, but IMT was unlikely to offer more analgesic effects than PBT. Even though many patients desired a TENS prescription, 50% still reported at least "slight pain relief" from PBT. Differences for gender and incident pain aspects demand future trials.

Practice review: Evidence-based and effective management of pain in patients with advanced cancer.

BACKGROUND: Pain of a moderate or severe intensity affects over half of patients with advanced cancer and remains undertreated in at least one-third of these patients. AIM: The aim of this study was to provide a pragmatic overview of the evidence supporting the use of interventions in pain management in advanced cancer and to identify where encouraging preliminary results are demonstrated but further research is required. DESIGN: A scoping review approach was used to examine the evidence supporting the use of guideline-recommended interventions in pain management practice. DATA SOURCES: National or international guidelines were selected if they described pain management in adult cancer patients and were written within the last 5 years in English. The Cochrane Database of Systematic Reviews (January 2014 to January 2019) was searched for 'cancer' AND 'pain' in the title, abstract or keywords. A MEDLINE search was also made. RESULTS: A strong opioid remains the drug of choice for treating moderate or severe pain. Bisphosphonates and radiotherapy are also effective for cancer-related bone pain. Optimal management requires a tailored approach, support for self-management and review of treatment outcomes. There is likely a role for non-pharmacological approaches. Paracetamol should not be used in patients taking a strong opioid to treat pain. Cannabis-based medicines are not recommended. Weak opioids, ketamine and lidocaine are indicated in specific situations only. CONCLUSION: Interventions commonly recommended by guidelines are not always supported by a robust evidence base. Research is required to evaluate the efficacy of non-steroidal anti-inflammatory drugs, anti-convulsants, anti-depressants, corticosteroids, some invasive anaesthetic techniques, complementary therapies and transcutaneous electrical nerve stimulation.

Cannabinoids for adult cancer-related pain: systematic review and meta-analysis.

OBJECTIVES: There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the beneficial and adverse effects of cannabis/cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults. METHODS: Systematic review and meta-analysis to identify randomised controlled trials of cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults to determine the effect on pain intensity (primary outcome) and adverse effects, including dropouts. Searches included Embase, MEDLINE, PsycINFO, Web of Science, ClinicalTrials.gov, Cochrane and grey literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. RESULTS: We identified 2805 unique records, of which six randomised controlled trials were included in this systematic review (n=1460 participants). Five studies were included in the meta-analysis (1442 participants). All had a low risk of bias. There was no difference between cannabinoids and placebo for the difference in the change in average Numeric Rating Scale pain scores (mean difference -0.21 (-0.48 to 0.07, p=0.14)); this remained when only phase III studies were meta-analysed: mean difference -0.02 (-0.21 to 0.16, p=0.80). Cannabinoids had a higher risk of adverse events when compared with placebo, especially somnolence (OR 2.69 (1.54 to 4.71), p<0.001) and dizziness (OR 1.58 (0.99 to 2.51), p=0.05). No treatment-related deaths were reported. Dropouts and mortality rates were high. CONCLUSIONS: Studies with a low risk of bias showed that for adults with advanced cancer, the addition of cannabinoids to opioids did not reduce cancer pain. TRIAL REGISTRATION NUMBER: CRD42018107662.

The myopic shift associated with hyperbaric oxygen administration is reduced when using a mask delivery system compared to a hood - a randomised controlled trial.

INTRODUCTION: A temporary myopic shift is a well-recognized complication of hyperbaric oxygen treatment (HBOT). Oxidation of proteins in the crystalline lens is the likely cause. Direct exposure of the eye to hyperbaric oxygen may exacerbate the effect. Our aim was to measure the magnitude of the myopic shift over a course of HBOT when using two different methods of oxygen delivery. METHODS: We conducted a randomised trial of oxygen delivery via hood versus oronasal mask during a course of 20 and 30 HBOT sessions. Subjective refraction was performed at baseline and after 20 and 30 sessions. We repeated these measurements at four and 12 weeks after completion of the course in those available for assessment. RESULTS: We enrolled 120 patients (mean age 57.6 (SD 11.2) years; 81% male). The myopic shift was significantly greater after both 20 and 30 sessions in those patients using the hood. At 20 treatments: refractory change was -0.92 D with hood versus -0.52 D with mask, difference 0.40 D (95% CI 0.22 to 0.57, P < 0.0001); at 30 treatments: -1.25 D with hood versus -0.63 with mask, difference 0.62 D (95% CI 0.39 to 0.84, P < 0.0001). Recovery was slower and less complete in the hood group at both four and 12 weeks. CONCLUSIONS: Myopic shift is common following HBOT and more pronounced using a hood system than an oronasal mask. Recovery may be slower and less complete using a hood. Our data support the use of an oronasal mask in an air environment when possible.

Is there a role for hyperbaric oxygen therapy in the treatment of refractory wounds of rare etiology?

INTRODUCTION: Delayed wound healing indicates wounds that have failed to respond to more than 4-6 weeks of comprehensive wound care. Wounds with delayed healing are a major source of morbidity and a major cost to hospital and community healthcare providers. Hyperbaric oxygen therapy (HBOT) is a treatment designed to increase the supply of oxygen to wounds and has been applied to a variety of wound types. This article reviews the place of HBOT in the treatment of non-healing vasculitic, calcific uremic arteriolopathy (CUA), livedoid vasculopathy (LV), pyoderma gangrenosum (PG) ulcers. METHODS: We searched electronic databases for research and review studies focused on HBOT for the treatment of delayed healing ulcers with rare etiologies. We excluded HBOT for ulcers reviewed elsewhere. RESULTS: We included a total of three case series and four case reports including 63 participants. Most were related to severe, non-healing ulcers in patients with vasculitis, CUA, LV, and PG. There was some evidence that HBOT may improve the healing rate of wounds by increasing nitric oxide (NO) levels and the number of endothelial progenitor cells in the wounds. HBOT may also improve pain in these ulcers. CONCLUSION: We recommend the establishment of comprehensive and detailed wound care registries to rapidly collect prospective data on the use of HBOT for these problem wounds. There is a strong case for appropriately powered, multi-centre randomized trials to establish the true efficacy and cost-effectiveness of HBOT especially for vasculitis ulcers that have not improved following immunosuppressive therapy.

Emerging indications for hyperbaric oxygen.

PURPOSE OF REVIEW: To identify and discuss emerging trends in the therapeutic use of hyperbaric oxygen. RECENT FINDINGS: There has been a maturing of the clinical evidence to support the treatment of sudden hearing loss, a wide range of problematic chronic wound states and the prevention and treatment of end-organ damage associated with diabetes mellitus. On the other hand, the controversy continues concerning the use of hyperbaric oxygen therapy (HBOT) to treat sequelae of mild traumatic brain injury. HBOT remains poorly understood by many medical practitioners despite more than 50 years of clinical practice. Pharmacological actions arise from increased pressures of oxygen in the blood and tissues. Most therapeutic mechanisms identified are not the simple result of the reoxygenation of hypoxic tissue, but specific effects on immunological and metabolic pathways by this highly reactive element. HBOT remains controversial despite biological plausibility and a solid clinical evidence base in several disease states. SUMMARY: Multiple proposals for new indications for HBOT continue to emerge. Although many of these will likely prove of limited clinical importance, some show significant promise. Responsible practitioners remain acutely aware of the need for high-quality clinical evidence before introducing emerging indications into routine practice.

Assessment of hyperbaric patients at risk of malnutrition using the Malnutrition Screening Tool - a pilot study.

BACKGROUND: Nutritional assessment and support is essential for wound management. The hyperbaric oxygen clinic is a unique outpatient service where chronically unwell patients present daily for hyperbaric oxygen treatment (HBOT) over several weeks, allowing time for effective nutritional intervention. This is the first study to examine the prevalence of those at risk of malnutrition in a cohort of hyperbaric medical patients. METHODS: A prospective study was undertaken over six months. Following consent, 39 enrolled patients had the Malnutrition Screening Tool and Baseline Characteristic Collection Form completed. Those at risk of malnutrition were given an option to be assessed by a dietitian to complete a Subjective Global Assessment (SGA). At the completion of treatment, the patients completed a questionnaire. RESULTS: Twelve of the 39 patients screened were at risk of malnutrition using our screening process. Of these, all the patients with available SGA results were diagnosed with moderate to severe malnutrition. Patients receiving HBOT for non-healing wounds and osteoradionecrosis were most at risk of malnutrition. CONCLUSION: The prevalence of patients being at risk of malnutrition in our hyperbaric medical service was about one in three. Malnutrition screening should be part of routine patient assessment in order to ensure patients receive timely nutritional intervention. This may improve wound healing.

Oral nitrite restores age-dependent phenotypes in eNOS-null mice.

Alterations in the synthesis and bioavailability of NO are central to the pathogenesis of cardiovascular and metabolic disorders. Although endothelial NO synthase-derived (eNOS-derived) NO affects mitochondrial long-chain fatty acid ß-oxidation, the pathophysiological significance of this regulation remains unclear. Accordingly, we determined the contributions of eNOS/NO signaling in the adaptive metabolic responses to fasting and in age-induced metabolic dysfunction. Four-month-old eNOS-/- mice are glucose intolerant and exhibit serum dyslipidemia and decreased capacity to oxidize fatty acids. However, during fasting, eNOS-/- mice redirect acetyl-CoA to ketogenesis to elevate circulating levels of ß-hydroxybutyrate similar to wild-type mice. Treatment of 4-month-old eNOS-/- mice with nitrite for 10 days corrected the hypertension and serum hyperlipidemia and normalized the rate of fatty acid oxidation. Fourteen-month-old eNOS-/- mice exhibited metabolic derangements, resulting in reduced utilization of fat to generate energy, lower resting metabolic activity, and diminished physical activity. Seven-month administration of nitrite to eNOS-/- mice reversed the age-dependent metabolic derangements and restored physical activity. While the eNOS/NO signaling is not essential for the metabolic adaptation to fasting, it is critical for regulating systemic metabolic homeostasis in aging. The development of age-dependent metabolic disorder is prevented by low-dose replenishment of bioactive NO.

The effectiveness of hyperbaric oxygen therapy for healing chronic venous leg ulcers: A randomized, double-blind, placebo-controlled trial.

Over 30% of venous leg ulcers do not heal despite evidence-based treatment. This study aimed to determine the effectiveness of Hyperbaric Oxygen Therapy (HBOT) as an adjunct treatment for nonhealing venous leg ulcers. A randomized, double-blind, parallel group, placebo-controlled trial was undertaken in three hyperbaric medicine units. Adults with a venous leg ulcer, Transcutaneous Oxygen Measurement indicative of a hypoxic wound responsive to oxygen challenge, and without contraindications for HBOT; were eligible. Of 84 eligible patients, 10 refused and 74 enrolled. 43 participants achieved over 50% ulcer Percent Area Reduction (PAR) after four weeks of evidence-based care and were thus excluded from the intervention phase. Thirty-one participants were randomized to either 30 HBOT treatments (100% oxygen at 2.4 atmospheres absolute (ATA) for 80 minutes), or 30 "placebo" treatments, receiving a validated "sham" air protocol, initially pressurized to 1.2ATA, then cycled between 1.05-1.2ATA for eight minutes before settling at 1.05ATA. The primary outcome was numbers in each group completely healed. Secondary outcomes were ulcer PAR, pain and quality of life, 12 weeks after commencing interventions. The participants' mean age was 70 years (standard deviation (SD) 12.9) and median ulcer duration at enrolment was 62 weeks (range 4-3120). At 12 weeks, there was no significant difference between groups in the numbers completely healed. The HBOT intervention group had a mean of 95 (SD 6.53) ulcer PAR, compared to 54 (SD 67.8) mean PAR for the placebo group (t = -2.24, p = 0.042, mean difference -40.8, SE 18.2) at 12 weeks. HBOT may improve refractory healing in venous leg ulcers, however patient selection is important. In this study, HBOT as an adjunct treatment for nonhealing patients returned indolent ulcers to a healing trajectory.