Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p < 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival

Referrals to a facial pain service

AIM: To assess the quality of referral letters to a facial pain service and highlight the key requirements of such letters. METHOD: The source of all referral letters to the service for five years was established. For one year the information provided in 94 referrals was assessed. Using a predetermined checklist of essential information the referral letters were compared to these set criteria. RESULTS: The service received 7,001 referrals and, on average, general dental practitioners (GDPs) referred 303 more patients per year than general medical practitioners (GMPs). Seventy-one percent of all referrals were from primary care practitioners, the rest were from specialists. Over 70% of GMP and 52% of GDP letters included a past medical history, with GMPs more likely to suggest a possible diagnosis and include previous secondary care referrals. The mean score for GMP referrals compared to the standard proforma (maximum of 12) was 5.6 and for GDP referrals 5.0. A relevant drug history was included by 75.6% GMP compared to 38.7% of GDPs. GMPs were more likely to include any relevant mental health history. CONCLUSIONS: The overall quality of referral letters is low which makes it difficult for the specialists to provide robust treatment plans

Susceptibility of T cell receptor-α chain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus

The anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-α(–/–) mice and B6 TCR-δ(–/–) mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-α(–/–) mice with low FU (0·2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2·0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-δ(–/–) mice at a very low incidence. Specifically, the skin lesions of TCR-α(–/–) mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE