Nitrous oxide-induced neurotoxicity: A case report and literature review.

Nitrous oxide is an increasingly popular recreational drug. However, recurrent or prolonged use can be associated with nitrous oxide toxicity, with numerous reports of harm documented in the literature. Nitrous oxide irreversibly binds and inactivates vitamin B12, which is an important co-factor in metabolic pathways involved in DNA and myelin synthesis. Toxicity is therefore associated with vitamin B12 deficiency-related syndromes, primarily involving haematological and neurological systems. As a "legal high", nitrous oxide use has attracted repeated health warnings from experts. An awareness and understanding of the pathophysiology and management of nitrous oxide toxicity is therefore important for clinicians. We discuss the case of a 29-year-old man presenting with nitrous oxide-induced sensorimotor neuropathy and review the existing literature surrounding toxicity.

The effect of 50% oxygen on PtCO2 in patients with stable COPD, bronchiectasis, and neuromuscular disease or kyphoscoliosis: randomised cross-over trials.

BACKGROUND: High-concentration oxygen therapy causes increased arterial partial pressure of carbon dioxide (PaCO2) in patients with COPD, asthma, pneumonia, obesity and acute lung injury. The objective of these studies was to investigate whether this physiological response to oxygen therapy occurs in stable patients with neuromuscular disease or kyphoscoliosis, and bronchiectasis. METHODS: Three randomised cross-over trials recruited stable patients with neuromuscular disease or kyphoscoliosis (n = 20), bronchiectasis (n = 24), and COPD (n = 24). Participants were randomised to receive 50% oxygen and 21% oxygen (air), each for 30 min, in randomly assigned order. The primary outcome was transcutaneous partial pressure of carbon dioxide (PtCO2) at 30 min. The primary analysis was a mixed linear model. RESULTS: Sixty six of the 68 participants had baseline PtCO2 values < 45 mmHg. The intervention baseline adjusted PtCO2 difference (95% CI) between oxygen and room air after 30 min was 0.2 mmHg (- 0.4 to 0.9), P = 0.40; 0.5 mmHg (- 0.2 to 1.2), P = 0.18; and 1.3 mmHg (0.7 to 1.8), P < 0.001, in the neuromuscular/kyphoscoliosis, bronchiectasis and COPD participants respectively. CONCLUSIONS: The small increase in PtCO2 in the stable COPD patients with high-concentration oxygen therapy contrasts with the marked increases in PaCO2 seen in the setting of acute exacerbations of COPD. This suggests that the model of studying the effects of high-concentration oxygen therapy in patients with stable respiratory disease is not generalisable to the use of oxygen therapy in the acute clinical setting. Appropriate studies of high-concentration compared to titrated oxygen in acute clinical settings are needed to determine if there is a risk of oxygen-induced hypercapnia in patients with neuromuscular disease, kyphoscoliosis or bronchiectasis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000970549 Registered 16/9/15, ACTRN12615000971538 Registered 16/9/15 and ACTRN12615001056583 Registered 7/10/15.

Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993-2012).

BACKGROUND: International time trends in asthma mortality have been strongly affected by changes in management and in particular drug treatments. However, little is known about how asthma mortality has changed over the past decade. In this study, we assessed these international trends. METHODS: We collated age-standardised country-specific asthma mortality rates in the 5-34 year age group from the online WHO Mortality Database for 46 countries. To be included in the analysis, we specified that a country must have 10 years of complete data in the WHO Mortality Database between 1993 and 2012. In the absence of consistent and accurate asthma prevalence and prescribing data, we chose to use a locally weighted scatter plot smoother (LOESS) curve, weighted by the individual country population in the 5-34-year age group to show the global trends in asthma mortality rates with time. FINDINGS: Of the 46 countries included in the analysis of asthma mortality, 36 were high-income countries, and 10 were middle-income countries. The LOESS estimate of the global asthma mortality rate was 0·44 deaths per 100 000 people (90% CI 0·39-0·48) in 1993 and 0·19 deaths per 100 000 people (0·18-0·21) in 2006. Despite apparent further reductions in some countries and regions of the world, there was no appreciable change in global asthma mortality rates from 2006 through to 2012, when the LOESS estimate was also 0·19 deaths per 100 000 people (0·16-0·21). INTERPRETATION: The trend for reduction in global asthma mortality observed since the late 1980s might have stalled, with no appreciable difference in a smoothed LOESS curve of asthma mortality from 2006 to 2012. Although better implementation of established management strategies that have been shown to reduce mortality risk is needed, to achieve a further substantive reduction in global asthma mortality novel strategies will also be required. FUNDING: The Medical Research Institute of New Zealand, which is supported by Health Research Council of New Zealand Independent Research Organisation.

The effect of adjusting LDL-cholesterol for Lp(a)-cholesterol on the diagnosis of familial hypercholesterolaemia.

BACKGROUND: Familial hypercholesterolaemia (FH) diagnostic tools help prioritise patients for genetic testing and include LDL-C estimates commonly calculated using the Friedewald equation. However, cholesterol contributions from lipoprotein(a) (Lp(a)) can overestimate 'true' LDL-C, leading to potentially inappropriate clinical FH diagnosis. OBJECTIVE: To assess how adjusting LDL-C for Lp(a)-cholesterol affects FH diagnoses using Simon Broome (SB) and Dutch Lipid Clinic Network (DLCN) criteria. METHODS: Adults referred to a tertiary lipid clinic in London, UK were included if they had undergone FH genetic testing based on SB or DLCN criteria. LDL-C was adjusted for Lp(a)-cholesterol using estimated cholesterol contents of 17.3%, 30% and 45%, and the effects of these adjustments on reclassification to 'unlikely' FH and diagnostic accuracy were determined. RESULTS: Depending on the estimated cholesterol content applied, LDL-C adjustment reclassified 8-23% and 6-17% of patients to 'unlikely' FH using SB and DLCN criteria, respectively. The highest reclassification rates were observed following 45% adjustment in mutation-negative patients with higher Lp(a) levels. This led to an improvement in diagnostic accuracy (46% to 57% with SB, and 32% to 44% with DLCN following 45% adjustment) through increased specificity. However all adjustment factors led to erroneous reclassification of mutation-positive patients to 'unlikely' FH. CONCLUSION: LDL-C adjustment for Lp(a)-cholesterol improves the accuracy of clinical FH diagnostic tools. Adopting this approach would reduce unnecessary genetic testing but also incorrectly reclassify mutation-positive patients. Health economic analysis is needed to balance the risks of over- and under-diagnosis before LDL-C adjustments for Lp(a) can be recommended.

Potential Association Between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine.

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.

Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: a randomised controlled trial.

OBJECTIVE: To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis. DESIGN: Prospective parallel randomised controlled open-label superiority trial. SETTING: 76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017. PARTICIPANTS: 952 adults randomised within the first 72 hours of a herpes simplex labialis episode. INTERVENTIONS: Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily. OUTCOME MEASURES: The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability. RESULTS: Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported. CONCLUSION: There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis. TRIAL REGISTRATION NUMBER: ACTRN12615000648527;Post-results.

Effect of active temperature management on mortality in intensive care unit patients.

OBJECTIVE: To evaluate the effect of active temperature management on mortality, intensive care unit (ICU) and hospital length of stay, as well as the relative efficacy of antipyretic medications and physical cooling devices for achieving reductions in temperature in critically ill adults. DESIGN, SETTING AND PARTICIPANTS: Systematic review and meta-analysis of randomised controlled trials (RCTs) investigating treatments administered to febrile patients in order to reduce body temperature. Fifteen studies reporting results from 13 RCTs met our eligibility criteria. INTERVENTIONS: Treatments administered to reduce body temperature were defined as physical cooling, nonsteroidal anti-inflammatory drugs, paracetamol, or any combination of these. MAIN OUTCOME MEASURES: The primary outcome variable was all-cause mortality at the longest time point after randomisation. Secondary outcomes were ICU and hospital length of stay, and body temperature 12 hours after randomisation. RESULTS: Active temperature control had no statistically significant association with mortality (odds ratio, 1.01; 95% confidence interval [CI], 0.81-1.28; P = 0.95, for fixed effects). There was no statistically significant association between active temperature management and ICU or hospital length of stay. Active temperature management was associated with a statistically significant reduction in temperature. The fixed effects estimate for the active minus control treatment for pharmaceutical management was -0.62C (95% CI, -0.72C to -0.51C; P < 0.001) and for physical cooling was -1.59C (95% CI, -1.82C to -1.35C; P < 0.001). CONCLUSIONS: Active temperature management neither increased nor decreased mortality risk in critically ill adults. When the therapeutic goal is to reduce body temperature, physical cooling approaches may be more effective than pharmacological measures in critically ill adults.

A feasibility study: association between gut microbiota enterotype and antibody response to seasonal trivalent influenza vaccine in adults.

Objective: We investigated the potential feasibility of a randomized controlled trial of a nutritional intervention that may alter human gut microbiota and support immune defence against respiratory tract infection in adults (Proposed Study). Methods: In total, 125 healthy adults aged 18-64 participated in a 6-month study that measured antibody response to the seasonal trivalent influenza vaccine. We assessed completion rates, procedure adherence rates and the influence of possible exclusion criteria on potential recruitment into the Proposed Study. We examined whether the gut microbiota could be categorised into enterotypes, and whether there was an association between enterotypes and the antibody response to the influenza vaccine. Results: The participant completion rate was 97.6% (95% CI 93.1-99.5%). The proportions (95% CI) of participants who may be excluded for antibiotic or corticosteroid use in the 30 days prior to the study, or due to receiving the influenza vaccine in the previous two years were 9.6% (5.1-16.2), 8.0% (3.9-14.2) and 61.6% (52.5-70.2), respectively. All participants were stratified into four gut microbiota enterotypes. There was no association between these enterotypes and the antibody response to the influenza vaccine, although the study was not powered for this outcome. Conclusion: This study design is suitable for the Proposed Study. The completion rate is likely to be high, although exclusion criteria should be selected with care. Further analyses of gut microbiota composition or function in association with antibody and immune responses are warranted to explore the role of host-microbiota interactions on protective immunity.

Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a secondary analysis of data from a randomised controlled trial.

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94(0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen. RELIEVER INHALER OVERUSE AND DELAY IN MEDICAL REVIEW IN ASTHMA: In asthma, overuse of beta-agonist reliever medication and delay in seeking medical review in an exacerbation are linked to asthma deaths. Janine Pilcher at the Medical Research Institute of New Zealand, and co-workers, conducted a review of data from a study of 303 adult patients with severe asthma, followed over 24 weeks. The patients were allocated to either a budesonide/formoterol, or a salbutamol inhaler to take for symptom relief, in addition to their maintenance treatment. Inhalers were fitted with electronic monitors, to accurately document every use. In both groups, on 90% of days when an exacerbation requiring excess use of an inhaler occurred, patients did not follow-up with medical professionals within 48 h as advised. Further, in both groups, 'extreme' reliever inhaler use was recorded at least once in around one in four patients.

Asthma and Respiratory Foundation NZ adult asthma guidelines: a quick reference guide.

The purpose of the Asthma and Respiratory Foundation NZ Adult Asthma Guidelines is to provide simple, practical and evidence-based recommendations for the diagnosis, assessment and management of asthma in adults (aged 16 and over) in a quick reference format. The intended users are health professionals responsible for delivering asthma care in the community and hospital Emergency Department settings, and those responsible for the training of such health professionals.

Breast implant extrusion related to Herpesviridae.

INTRODUCTION: We present a case of wound dehiscence in a patient with clinical features of herpes zoster. PRESENTATION OF CASE: A 44 year old woman, with a history of recurrent herpes zoster infection, presented to the accident and emergency department with the extrusion of a left sided tear-drop shaped euro-silicone breast implant from an old surgical scar. A month prior to admission, this patient had developed unilateral crops of vesicles along the surgical scar which was apposing her left infra-mammary fold. This was preceded by fatigue and neuralgia. Histology revealed acute inflammation related to a probable Herpesviridae infection. DISCUSSION: In this report we discuss the first case of a viral infection predisposing to a wound dehiscence occurring in an old surgical scar. CONCLUSION: This case report illustrates the real but rare possibility of recurrent herpes zoster causing gradual thinning of an old surgical scar. This resulted in an extrusion of the underlying breast implant.