Let's be more conscious about the misuse of nitrous oxide.

Following the 'No laughing matter' article published in 2020 by Dr Croser, this paper further highlights the increasingly concerning problem of the illicit use of nitrous oxide.Since 1884, the benefits of nitrous oxide have been exploited in the field of dentistry. Its analgesic and mild anaesthetic properties, alongside suggestive hypnosis and reassurance, are often enough to relieve the anxieties of our patients sufficiently to enable dental treatment. When used appropriately, it has a wide margin of safety and no significant side effects. However, the instantaneous feeling of euphoria experienced after inhaling the drug lends itself to recreational use. This is becoming more popular among the younger generations of the population; the drug is both incredibly easy and cheap to purchase, at only 22p a cannister. More than half a million teenagers and young adults are using this drug at present. Grieving parents of teenagers who have tragically lost their lives to this drug are pleading for people to stop, and for The Advisory Council on the Misuse of Drugs to criminalise nitrous oxide.Let's be more aware of the dangers of nitrous oxide, encourage those to seek help when they need it and refer to local drug support services - it could help to save lives.

The effect of grape interventions on cognitive and mental performance in healthy participants and those with mild cognitive impairment: a systematic review of randomized controlled trials.

CONTEXT: The prevalence of cognitive and mental health disorders are growing, and existing drug therapies do not treat the underlying cause. Grapes are a flavonoid-rich soft fruit and may therefore be beneficial to cognitive and mental health. OBJECTIVE: To systematically review evidence from randomized controlled trials investigating the acute and chronic effects of grape interventions on measures of cognition and mood in healthy participants and those with mild cognitive impairment. DATA SOURCES: MEDLINE, The Cochrane Library and EMBASE were searched. DATA EXTRACTION AND ANALYSIS: Eight studies met the inclusion criteria: one considered acute interventions, 6 assessed chronic effects, and one assessed acute and chronic effects of grapes. The chronic studies found improvements in some cognitive domains (eg, memory, motor skills, or executive function). Acute studies found no consistent effect on memory but saw improvements in reaction time. CONCLUSIONS: Differences in study design, dosages, and outcome tests hindered between-study comparison. Even so, the results across studies show that grapes can enhance some aspects of cognition, after both acute and chronic interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020193062.

Single centre, real-world experience of perioperative rFIXFc use in adult patients with haemophilia B undergoing major and minor surgery.

INTRODUCTION: Recombinant factor IX fusion protein concentrate (rFIXFc) is increasingly used for prophylaxis in people with haemophilia B (PWHB), but experience in the perioperative setting is limited. AIMS: To evaluate real-world perioperative factor usage, bleeding and complications in PWHB (≥18 years) who received rFIXFc for surgical haemostasis and to describe the treatment regimens used. METHODS: Single centre, retrospective review of all PWHB who underwent a major or minor surgical procedure between June 2017 and July 2020 and received rFIXFc perioperatively for maintenance of surgical haemostasis. RESULTS: A total of 56 PWHB (45 male and 11 female), including people with mild (n = 32), moderate (n = 4) and severe (n = 20) haemophilia B, underwent 11 major and 131 minor procedures with rFIXFc for surgical haemostasis. Haemostasis was rated as excellent (9/11) or good (2/11) in all major procedures. Median total rFIXFc consumption for orthopaedic surgeries was 972 IU/kg (range 812-1031 IU/kg) and for other major (non-orthopaedic) surgeries was 323 IU/kg (range 167-760 IU/kg). The median number of perioperative rFIXFc infusions was 19 (range 17-26) for orthopaedic surgery and 7 (range 5-17) for other major surgeries. The number of infusions in the postoperative period was determined by procedure and patient factors. Complications included bowel ileus and wound infection. Most minor procedures were managed with single infusion of rFIXFc, with no bleeding complications in 95% of minor procedures. There were no thromboembolic events or inhibitor formation. CONCLUSION: This unique data provides real-world evidence that rFIXFc is safe and effective in achieving haemostasis in PWHB undergoing surgery.

Using mass spectrometry to overcome the longstanding inaccuracy of a commercially-available clinical testosterone immunoassay.

Accurate measurement of testosterone is important for the diagnosis of gonadal disorders in men, women, and children. Testosterone measurement has limited accuracy at low concentrations by most commercially available immunoassays. We aimed to develop an LC-MS/MS assay to address the inaccuracy of the in-house immunoassay observed over the past decade and to replace it with the new assay. Testosterone in serum/plasma was extracted with commercial supported liquid extraction plates. Method validation was performed following the CLSI C62-A guideline. A total of 126 samples were used for method comparison between the Beckman UniCel DxI immunoassay and LC-MS/MS. Results by immunoassay were 20% lower compared with LC-MS/MS and had minimal correlation (R2 = 0.403) with LC-MS/MS below 100 ng/dL. When comparing specimens from the Accuracy-Based Survey from the College of American Pathologists, the newly developed assay agreed well with the CDC reference measurement procedure. In summary, immunoassay measurement of testosterone can be significantly inaccurate, especially at low concentrations. The newly developed LC-MS/MS assay provides accurate results across the entire measurable range.

Real-world outcomes with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: Longitudinal follow-up in a national adult cohort.

INTRODUCTION: In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half-life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis. AIMS: To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real-world setting. METHODS: Data collected retrospectively from electronic diaries and medical records of PWSHB for a two-year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment. RESULTS: 28 PWSHB (≥18 years) were enrolled, and at switchover 79% were receiving prophylaxis and 21% episodic treatment with SHL rFIX. At 24 months following switchover, all remained on rFIXFc prophylaxis with reduced infusion frequency; median dose per infusion once weekly (55 IU/kg, 20/28), every 10 days (63 IU/kg, 2/28) or every 14 days (98 IU/kg, 6/28). Median annualised bleed rate improved significantly on rFIXFc prophylaxis (2.0 versus 3.3 on SHL FIX) (p = 0.01). Median FIX trough level with once-weekly infusions was 0.09 IU/ml (0.06-0.14 IU/ml). Management of bleeding episodes was similar with rFIXFc and SHL rFIX; one infusion was sufficient to treat 74% and 77% of bleeds, respectively, with similar total median treatment per bleeding episode. Factor consumption reduced by 28% with rFIXFc prophylaxis (57 IU/kg/week, range 40-86 IU/kg/week) compared with SHL rFIX (79 IU/kg/week, range 44-210 IU/kg/week) (p = 0.002). CONCLUSION: This study provides important insights into real-world experience of switching to rFIXFc prophylaxis in an adult population, demonstrating high rates of prophylaxis, with reduced infusion frequency, bleeding and FIX consumption.

Telehealth for delivery of haemophilia comprehensive care during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic caused an unprecedented impact to haemophilia healthcare delivery. In particular, rapid implementation of telehealth solutions was required to ensure continued access to comprehensive care. AIMS: To explore patient and healthcare provider (HCP) experience of telehealth in a European Haemophilia Comprehensive Care Centre. METHOD: A systematic evaluation was performed to survey patient and HCP experience and compare clinical activity levels with telehealth to in-person attendances. RESULTS: Public health measures implemented in March 2020 to reduce COVID-19 spread resulted in a 63% decrease in medical/nursing clinic consultation activity compared to the same period in 2019. Implementation of digital care pathways resulted in marked increase in activity (52% greater than 2019). Importantly, enhanced patient engagement was noted, with a 60% reduction in non-attendance rates. Survey of patients who had participated in medical/nursing teleconsultations demonstrated that teleconsultations improved access (79%), reduced inconvenience (82%), was easy to use (94%) and facilitated good communication with the HCP (97%). A survey exploring the telemedicine experience of HCPs, illustrated that HCPs were satisfied with teleconsultation and the majority (79%) would like to continue to offer teleconsultation as part of routine patient care. In addition to medical/nursing reviews, continued access to physiotherapy with virtual exercise classes for people with haemophilia and teleconsultation for acute dental issues was equally successful. CONCLUSION: During an unprecedented public health emergency, telehealth has enabled continued access to specialized haemophilia comprehensive care. Our novel findings show that this alternative is acceptable to both patients and HCPs and offers future novel opportunities.