No abstract

Nightshift working is associated with sleep deprivation, fatigue and attention/ concentration deficits which, in healthcare workers, may impact on patient safety. Clinical staff in the UK routinely work several 12 h nightshifts in a row at about 1-3 month intervals. We investigated the feasibility and acceptability of a crossover trial of melatonin administration in clinical staff working nightshifts with an exploration of effects on sleep measures and attention/concentration tasks. This was a pilot, double-blinded, randomized, placebo-controlled crossover feasibility trial in doctors and nurses working 3 consecutive nightshifts at a tertiary referral hospital in the UK. Twenty five male and female subjects were randomized to receive either 6mg Circadin™ slow release melatonin or placebo before sleep after each consecutive nightshift, followed by a washout period, before crossing over to the other experimental arm. We used actigraphy for objective assessment of sleep parameters. The trial design was feasible and acceptable to participants with negligible side effects, but elevated melatonin levels were prolonged during the active arm (P=0.016). Double digit addition testing, a concentration/attention task, improved with melatonin treatment (P<0.0001). Lapses of vigilance or judgement while doctors or nurses are working nightshifts could impact on patient safety and melatonin may be a useful intervention. This study supports the conclusion that a larger definitive trial of this design is both feasible and safe.

Melatonin is a neuroendocrine hormone which regulates circadian rhythm and is also an antioxidant. The role of melatonin in pregnancy is emerging. The enzymes needed for endogenous synthesis of melatonin have been identified in the placenta, although the contribution to circulating maternal melatonin in normal pregnancy is unclear. This work aimed to determine serum levels of melatonin and its major metabolite 6-hydroxymelatonin sulfate (6-OHMS) in normal pregnant women during each trimester of pregnancy, and immediately after delivery. Blood samples were obtained from a cohort of healthy pregnant women during each trimester of pregnancy (n = 26), from women scheduled for elective Cesarean section (CS) before and after delivery (n = 15), along with placental samples, and from healthy non-pregnant women as controls (n = 30). Melatonin and its major metabolite, 6-OHMS, were measured using enzyme immunoassay. Levels of serum melatonin were significantly higher during pregnancy than in non-pregnant women (P = 0.025) and increased throughout pregnancy (P &lt; 0.0001). In women undergoing CS, serum melatonin decreased markedly 24 h after delivery (P = 0.0013). Similar results were seen for serum levels of 6-OHMS, and placental tissue 6-OHMS levels correlated with week of gestation at delivery (p = 0.018). In summary, maternal melatonin production is higher in pregnant than in non-pregnant women, increases significantly during pregnancy with highest levels in the third trimester, and decreases abruptly after delivery. These results suggest that the placenta is a major source of melatonin and supports a physiological role for melatonin in pregnancy.

Background:We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine.Methods:Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy.Results:In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05).Conclusions:Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups.

reduced anxiety and improved satisfaction but required a lot of time to use. 'Speaking' tracheostomy tubes (nine studies) generate audible voice of objectively good to excellent quality in the majority of patients with high levels of satisfaction and comfort. Computerised AAC (14 studies) led to reduced frustration and anxiety in many patients, even allowing complex conversation for several. For some, however, the technology barrier caused dissatisfaction. An electrolarynx (nine studies) was more effective in tracheostomy patients, although did not provide intelligible communication to all. Above cuff vocalisation (one study) produced voice with moderate to no dysphonia; but was ineffective in patients with altered anatomy or poor compliance. A wide variety of AAC strategies exist to enhance communication in patients dependent on MV, ranging from simple bedside intervention to more complex technologies. AAC has been shown to improve satisfaction and reduce frustration and anxiety in patients and facilitating even complex conversation in some. Further high-quality research is necessary to clarify which AAC device is best suited to individual patients, their condition, communication needs and capabilities at different stages of their illness.