Age specific trends in asthma mortality in England and Wales, 1983-95: results of an observational study.

OBJECTIVE: To determine trends in asthma mortality by age group in England and Wales during 1983-95. DESIGN: Observational study. SETTING: England and Wales. SUBJECTS: All deaths classified as having an underlying cause of asthma registered from 1 January 1983 to 31 December 1995. MAIN OUTCOME MEASURE: Time trends for age specific asthma deaths. RESULTS: Deaths in the age group 5-14 years showed an irregular downward trend during 1983-95; deaths in the age groups 15-44, 45-64, and 65-74 years peaked before 1989 and then showed a downward trend; and deaths in the age group 75-84 years peaked between 1988 and 1993 and subsequently dropped. Trends were: age group 5-14 years, 6% (95% confidence interval 3% to 9%); 15-44 years, 6% (5% to 7%); 45-64 years, 5% (4% to 6%); 65-74 years, 2% (1% to 3%). Deaths in the 75-84 and 85 and over categories plateaued. CONCLUSIONS: There are downward trends in asthma mortality in Britain, which may be due to increased use of prophylactic treatment.     

Neuropsychological consequences of volatile substance abuse: a population based study of secondary school pupils.

OBJECTIVE--To examine the effects of volatile substance abuse on neuropsychological functioning. DESIGN--A sample of index children and matched controls were identified by a two stage procedure. Firstly, over 5000 secondary school pupils completed a screening questionnaire, and, secondly, a sample of those who acknowledged volatile substance abuse and a matched sample of those who denied the practice were assessed in detail by means of (a) individually conducted interviews and (b) toxicological examination of breath samples (to exclude those intoxicated at the time of testing). SETTING--16 Local education authority secondary schools in London. SUBJECTS--160 Pupils aged 13-16: 80 index children who had abused volatile substances to the point of intoxication at least once (confirmed by interview) and 80 controls (confirmed by interview) matched for school year, sex, and ethnic background. MEASUREMENTS AND MAIN RESULTS--Neuropsychological functioning tests provided 35 main outcome measures and were administered blind. Data on educational test performance before substance abuse began were obtained retrospectively. Information on potentially confounding social factors, such as number of siblings, tenure of housing, and parents'' socioeconomic and employment state was also obtained. The index children performed significantly less well than the controls in tests of vocabulary, verbal intelligence quotient, full scale intelligence quotient, and a measure of impulsivity. When background social disadvantage was taken into account these differences were no longer significant. There were no significant associations between performance on psychological testing and frequency of abuse, and relations with other aspects of the children''s history of abuse were generally weak or unsystematic. Comparisons between the results of these tests and of educational tests taken before substance abuse produced equivocal findings. CONCLUSION--Volatile substance abuse, as commonly practised by secondary school pupils, is unlikely to result in neuropsychological impairment.     

Tobacco-Related Mortality among Persons with Mental Health and Substance Abuse Problems

The rate of cigarette smoking is greater among persons with mental health and/or substance abuse problems. There are few population-based datasets with which to study tobacco mortality in these vulnerable groups. The Oregon Health Authority identified persons who received publicly-funded mental health or substance abuse services from January 1996 through December 2005. These cases were then matched to Oregon Vital Statistics records for all deaths (N= 148,761) in the period 1999-2005. The rate of tobacco-related death rates was higher among persons with substance abuse problems only (53.6%) and those with both substance abuse and mental health problems (46.8%), as compared to the general population (30.7%). The rate of tobacco-related deaths among persons with mental health problems (30%) was similar to that in the general population. Persons receiving substance abuse treatment alone, or receiving both substance abuse and mental health treatment, were more likely to die and more likely to die prematurely of tobacco-related causes as compared to the general population. Persons receiving mental health services alone were not more likely to die of tobacco-related causes, but tobacco-related deaths occurred earlier in this population.     

UK legislation on analgesic packs: before and after study of long term effect on poisonings

Objective To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter.Design Before and after study.Setting Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002.Data sources Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK.Main outcome measures Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics.Results Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths.Conclusion Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.     

Selenium and zinc levels in volatile substance abusers

Plasma and erythrocyte levels of selenium (Se) and zinc (Zn) have not been investigated in volatile (inhalant) substance abusers previously, although changes in the activities of antioxidant enzymes resulting from oxidative damage caused by various constituents of volatile substances have been shown in a few animal and human studies. Concentrations of these two elements in erythrocytes and plasma of 37 adolescents with inhalant abuse were measured by atomic absorption spectrophotometry and compared with those of 37 age-matched healthy controls. Erythrocyte and plasma levels of Se and plasma level of Zn were significantly lower in the study group when compared to the control group. Chronic inhalation of volatile substances can decrease the plasma levels of Se and Zn and, thus, may lead to a decrease in the activity of antioxidant enzyme systems in adolescent abusers. The role of Se and Zn supplementation in children with inhalant abuse remains to be determined considering the reduced antioxidant activity resulting from deficiency of these trace elements.     

Death rates of characters in soap operas on British television: is a government health warning required?

OBJECTIVE: To measure mortality among characters in British soap operas on television. DESIGN: Cohort analysis of deaths in EastEnders and Coronation Street, supplemented by an analysis of deaths in Brookside and Emmerdale. MAIN OUTCOME MEASURES: Standardised mortality ratios and the proportional mortality ratio for deaths attributable to external causes (E code of ICD-9 (international classification of diseases, ninth revision). RESULTS: Staying alive in a television soap opera is not easy. Standardised mortality ratios for characters were among the highest for any occupation yet described (771 (95% confidence interval 415 to 1127) for characters in EastEnders), and this was not just because all causes of death were overrepresented. Deaths in soap operas were almost three times more likely to be from violent causes than would be expected from a character''s age and sex. A character in EastEnders was twice as likely as a similar character in Coronation Street to die during an episode. CONCLUSIONS: The most dangerous job in the United Kingdom is not, as expected, bomb disposal expert, steeplejack, or Formula One racing driver but having a role in one of the United Kingdom''s most well known soap operas. This is the first quantitative estimate of the size of the pinch of salt which should be taken when watching soap operas.     

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.     

Glutamatergic neurotransmission in alcoholism

Substance abuse and dependence is the most common psychiatric problem. Alcohol is the most commonly abused substance and most people who abuse other substance(s) abuse alcohol at the same time. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent via the glutamatergic system. Ethanol disrupts glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor and by promoting neuronal toxicity through upregulation of the NMDA receptor density. Therefore, short-term/acute ethanol treatment results in a blockade of NMDA receptor-mediated neurotransmission and apoptotic cell death by inhibiting the trophic effect mediated by the NMDA receptor whereas chronic ethanol treatment and withdrawal results in an enhanced toxic response toward glutamate. The neurobiology of human alcoholism such as ethanol intoxication, dependence, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome can be better understood as a spectrum of consequences of ethanol's effect on the NMDA glutamatergic system.     

Bath salts and synthetic cathinones: An emerging designer drug phenomenon

Synthetic cathinones are an emerging class of designer drugs abused for psychostimulant and hallucinogenic effects similar to cocaine, methylenedioxymethamphetamine (MDMA), or other amphetamines. Abuse of synthetic cathinones, frequently included in products sold as ‘bath salts’, became prevalent in early 2009, leading to legislative classification throughout Europe in 2010 and schedule I classification within the United States in 2011. Recent pre-clinical and clinical studies indicate that dysregulation of central monoamine systems is a principal mechanism of synthetic cathinone action and presumably underlie the behavioral effects and abuse liability associated with these drugs. This review provides insight into the development of synthetic cathinones as substances of abuse, current patterns of their abuse, known mechanisms of their action and toxicology, and the benefits and drawbacks of their classification.     

Hepatic reactions associated with ketoconazole in the United Kingdom.

Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.     

Incidence of AIDS and excess of mortality associated with HIV in haemophiliacs in the United Kingdom: report on behalf of the directors of haemophilia centres in the United Kingdom.

OBJECTIVE--To estimate the cumulative incidence of AIDS by time since seroconversion in haemophiliacs positive for HIV and to examine the evidence for excess mortality associated with HIV in those who had not yet been diagnosed as having AIDS. DESIGN--Analysis of data from ongoing national surveys. SETTING--Haemophilia centres in the United Kingdom. PATIENTS--A total of 1201 men with haemophilia who had lived in the United Kingdom during 1980-7 and were positive for HIV. INTERVENTION--None. END POINTS--Diagnosis of AIDS; death in those not diagnosed as having AIDS. MEASUREMENTS AND MAIN RESULTS--Estimation of cumulative incidence of AIDS and number of excess deaths in seropositive patients not diagnosed with AIDS. Median follow up after seroconversion was 5 years 2 months. Eight five patients developed AIDS. Cumulative incidence of AIDS five years after seroconversion was 4% among patients aged less than 25 at first test positive for HIV, 6% among those aged 25-44, and 19% among those aged greater than or equal to 45. There was little evidence that type or severity of haemophilia or type of factor VIII or IX that had caused HIV infection affected the rate of progression to AIDS. Mortality was increased among those who had not been diagnosed as having AIDS, especially among those with "AIDS related complex." Thirteen deaths were observed among 36 patients diagnosed as having AIDS related complex against 0.65 expected, and 34 deaths in 1080 other patients against 22.77 expected; both calculations were based on mortality rates observed in haemophiliacs in the United Kingdom in the late 1970s. CONCLUSIONS--Rate of progression to AIDS depended strongly on age. There is a substantial burden of fatal disease among patients positive for HIV who have not been formally diagnosed as having AIDS.     

Survivors of sexual abuse: clinical,lifestyle and reproductive consequences

BACKGROUND: In recent years, an increase in the prevalence of sexual abuse of women has been reported in Canada and elsewhere. However, there are few empirical data on the extent of the problem in Canadian aboriginal populations. The authors investigated the presence of a reported history of sexual abuse and other health determinants in a sample of women attending a community health centre with a substantial aboriginal population. This allowed determination of whether reported sexual abuse and its associated demographic and health-related effects were different for aboriginal and non-aboriginal women. METHODS: A sample of 1696 women was selected from women attending a community health centre in a predominantly low-income inner-city area of Winnipeg for a cross-sectional survey designed to study the association between sexual behavior and cervical infections. The survey was conducted between November 1992 and March 1995 and involved a clinical examination, laboratory tests and an interviewer-administered questionnaire. A substudy was conducted among 1003 women who were asked 2 questions about sexual abuse. RESULTS: The overall response rate for the main study was 87%. Of the 1003 women who were asked the questions about sexual abuse, 843 (84.0%) responded. Among the respondents, 368 (43.6%) were aboriginal. Overall, 308 (36.5%) of the respondents reported having been sexually abused, 74.0% of the incidents having occurred during childhood. The prevalence was higher among aboriginal women than among non-aboriginal women (44.8% v. 30.1%, p < 0.001). Women who had been sexually abused were younger when they first had sexual intercourse, they had multiple partners, and they had a history of sexually transmitted diseases. In addition, non-aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have had abnormal Papanicolaou smears. The proportion of smokers was higher among the abused women than among the non-abused women in both ethnic groups. INTERPRETATION: A history of sexual abuse was associated with other clinical, lifestyle and reproductive factors. This suggests that sexual abuse may be associated with subsequent health behaviors, beyond specific physical and psychosocial disorders. Aboriginal and non-aboriginal women who have suffered sexual abuse showed substantial differences in their subsequent health and health-related behaviours.     

Estimate of deaths attributable to passive smoking among UK adults: database analysis

Objective To estimate deaths from passive smoking in employees of the hospitality industry as well as in the general workforce and general population of the United Kingdom.Design Calculation, using the formula for population attributable proportion, of deaths likely to have been caused by passive smoking at home and at work in the UK according to occupation. Sensitivity analyses to examine impact of varying assumptions regarding prevalence and risks of exposure.Setting National UK databases of causes of death, employment, structure of households, and prevalences of active and passive smoking.Main outcome measures Estimates of deaths due to passive smoking according to age group (< 65 or ≥ 65) and site of exposure (domestic or workplace).Results Across the United Kingdom as a whole, passive smoking at work is likely to be responsible for the deaths of more than two employed people per working day (617 deaths per year), including 54 deaths in the hospitality industry each year. Each year passive smoking at home might account for another 2700 deaths in persons aged 20-64 years and 8000 deaths among people aged ≥ 65.Conclusion Exposure at work might contribute up to one fifth of all deaths from passive smoking in the general population aged 20-64 years, and up to half of such deaths among employees of the hospitality industry. Adoption of smoke free policies in all workplaces and reductions in the general prevalence of active smoking would lead to substantial reductions in these avoidable deaths.     

Mortality among male anaesthetists in the United Kingdom, 1957-83.

A cohort of 3769 male anaesthetists resident in the United Kingdom between 1957 and 1983 was followed up for a total of 51,431 person years of observation. All subjects were fellows of the Faculty of Anaesthetists and held full registration with the General Medical Council. With all men in social class I being taken as the standard, the standardised mortality ratio among anaesthetists for all causes of death was 68 (95% confidence interval 59 to 77) and the standardised mortality ratio for all cancers was 50 (95% confidence interval 36 to 67). There was no significant excess mortality from lymphomas or leukaemias, but 16 of the 221 deaths in anaesthetists were due to suicide, giving a standardised mortality ratio of 202 (95% confidence interval 115 to 328). When anaesthetists were compared with all doctors the standardised mortality ratio for suicide was only 114, a nonsignificant excess. These findings confirm that the risk of suicide among anaesthetists is twice as high as among other men in social class I but suggest that the risk does not differ significantly from that among doctors as a whole. There was no evidence of a significant excess risk of cancer, and, in particular, the small excess of cancer of the pancreas reported previously could not be confirmed.     

The relative risks and etiologic fractions of different causes of death and disease attributable to alcohol,tobacco and illicit drug use in Canada

BACKGROUND: In 1996 the number of deaths and admissions to hospital in Canada that could be attributed to the use of alcohol, tobacco and illicit drugs were estimated from 1992 data. In this paper we update these estimates to the year 1995. METHODS: On the basis of pooled estimates of relative risk, etiologic fractions were calculated by age, sex and province for 90 causes of disease or death attributable to alcohol, tobacco or illicit drugs; the etiologic fractions were then applied to national mortality and morbidity data for 1995 to estimate the number of deaths and admissions to hospital attributable to substance abuse. RESULTS: In 1995, 6507 deaths and 82,014 admissions to hospital were attributed to alcohol, 34,728 deaths and 194,072 admissions to hospital were attributed to tobacco, and 805 deaths and 6940 admissions to hospital were due to illicit drugs. INTERPRETATION: The use and misuse of alcohol, tobacco and illicit drugs accounted for 20.0% of deaths, 22.2% of years of potential life lost and 9.4% of admissions to hospital in Canada in 1995.     

Peripheral neuropathy following intentional inhalation of naphtha fumes.

Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused.     

Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients.

A well-defined relationship has to exist between substance concentrations in blood and in breath if blood-borne volatile organic compounds (VOCs) are to be used as breath markers of disease or health. In this study, the impact of inspired substances on this relationship was investigated systematically. VOCs were determined in inspired and expired air and in arterial and mixed venous blood of 46 mechanically ventilated patients by means of SPME, GC/MS. Mean inspired concentrations were 25% of expired concentrations for pentane, 7.5% for acetone, 0.7% for isoprene and 0.4% for isoflurane. Only if inspired concentrations were <5% did substance disappearance rates from blood and exhalation rates correlate well. Exhaled substance concentrations depended on venous and inspired concentrations. Patients with sepsis had higher n-pentane and lower acetone concentrations in mixed venous blood than patients without sepsis (2.27 (0.37-8.70) versus 0.65 (0.33-1.48) nmol L-1 and 69 (22-99) versus 18 (6.7-56) micromol L-1). n-Pentane and acetone concentrations in breath showed no differences between the patient groups, regardless whether or not expired concentrations were corrected for inspired concentrations. In mechanically ventilated patients, concentration profiles of volatile substances in breath may considerably deviate from profiles in blood depending on the relative amount of inspired concentrations. A simple correction for inspired substance concentrations was not possible. Hence, substances having inspired concentrations>5% of expired concentrations should not be used as breath markers in these patients without knowledge of concentrations in blood and breath.     

Deaths From Bites and Stings of Venomous Animals

Data abstracted from 34 death certificates indicate that the three venomous animal groups most often responsible for human deaths in California from 1960 through 1976 were Hymenoptera (bees, wasps, ants and the like) (56 percent), snakes (35 percent) and spiders (6 percent). An average incidence of 2.0 deaths per year occurred during these 17 years, or an average death rate of 0.01 per 100,000 population per year. Nearly three times more males than females died of venomous animal bites and stings. Half of the deaths from venomous snake bites occurred in children younger than 5 years of age. Susceptible persons 40 years or older appeared to be particularly vulnerable to hymenopterous insect stings and often quickly died of anaphylaxis. Fatal encounters with venomous animals occurred more often around the home than at places of employment or during recreational activities. Deaths resulting from spider bites are rare in California but many bites are reported. Medical practitioners are urged to seek professional assistance in identifying offending animals causing human discomfort and to use these animals'' scientific names on death certificates and in journal articles.     

Exudation of low molecular weight compounds (thiobismethane, methyl isocyanide, and methyl isothiocyanate) as a possible chemical defense mechanism in the marine sponge Ircinia felix

The volatile constituents of the marine sponge Ircinia felix were obtained by dynamic headspace extraction and analyzed by HRGC, HRGC-MS and HRGC-Odor at sniffing port. Fifty-nine volatiles were identified for the first time in the odor of this sponge. Hydrocarbons (32.9%), alcohols (17.8%) and carbonyl compounds (16.0%) predominated in the sponge volatile profile, followed by esters (11.6%), halogen compounds (8.6%), ethers (7.7%), nitrogen and/or sulfur compounds (4.6%) and carboxylic acids (0.8%). Among the identified volatiles, thiobismethane (commonly known as dimethylsulfide), methyl isocyanide and methyl isothiocyanate were found to be responsible for the nauseating and toxic smell emitted by the sponge and for the antimicrobial activity detected in the volatile extract. Exudation experiments in aquarium and in situ conditions revealed that thiobismethane, methyl isocyanide and methyl isothiocyanate are continuously released by the sponge. Upon injury, the concentration of these volatiles increased strongly. Hence, these substances form a chemical protective barrier which may help these sponges avoid fouling, compete for space, prevent infection in the short term, and/or signal generalist predators regarding the existence of other toxic substances in the internal tissues.