Home mechanical ventilation for amyotrophic lateral sclerosis: nasal compared to tracheostomy-intermittent positive pressure ventilation.

People with amyotrophic lateral sclerosis (ALS) usually die from respiratory failure unless they use mechanical ventilation (MV). Many die of respiratory failure without being adequately informed about the available options, such as MV that can provide symptomatic relief and prolong survival. The traditional method of MV used for persons with ALS has been tracheostomy-intermittent positive pressure ventilation (IPPV). However, the advent of nasal-IPPV has provided a new option for relieving respiratory symptoms and prolonging survival among selected individuals. The ALS Association Data on 75 ALS patients using MV is reviewed. Twenty-five patients used nasal-IPPV, all started electively. Survival with nasal-IPPV ranged from 6 to 64 months for non-bulbar patients, or until the onset of severe bulbar dysfunction when nasal-IPPV no longer was effective. Fifteen of these non-bulbar patients used nasal-IPPV from 20 to 24 h daily; one of these patients used nasal-IPPV continuously for 24 h daily for 24 months. One hundred percent of the users indicated they were glad they chose nasal-IPPV. In contrast, 50 have used tracheostomy-IPPV, usually as a result of emergency hospitalization without advance decision making. Twenty-five patients (50%) lived in a sub-acute skilled nursing facility (SNF) and only 18 of these (72%) were satisfied with their quality of life. Patients using tracheostomy-IPPV with good care are able to live many years: 27 of the 50 (54%) are still living, including one patient who is still living after 14 years of MV. In conclusion, home mechanical ventilation with nasal or tracheostomy-IPPV are options for selected people with ALS. Nasal-IPPV offers may advantages; it was only used when MV was planned and desired. Nasal-IPPV can be used unless bulbar impairment is severe.

Patients with amyotrophic lateral sclerosis receiving long-term mechanical ventilation. Advance care planning and outcomes.

OBJECTIVE: To examine advance care planning and outcomes of patients with amyotrophic lateral sclerosis (ALS) receiving long-term mechanical ventilation (LTMV). DESIGN: Case series. SETTING: Population-based study in homes and chronic care facilities in four states, and Home Ventilator Program of California Kaiser Permanente. PATIENTS: Seventy-five ALS patients receiving LTMV were identified; 11 died prior to interview, and 6 were totally locked in; 50 of 58 (86%) who were able to communicate consented to structured interviews, of whom 36 lived at home and 14 in an institution. RESULTS: Thirty-eight patients (76%) had completed advance directives, and 96% wanted them. Thirty-eight patients wished to stop LTMV in certain circumstances, of whom 30 had completed advance directives. Those who had completed advance directives were more likely to have communicated their preference, to stop LTMV to family and physician than those who had not (76 vs 29%; p = 0.05). Patients living at home rated their quality of life on a 10-point scale better than those in an institution (7.2 vs 5.6; p = 0.0052), and their yearly expenses were less ($136,560 vs $366,852; p = 0.0018). CONCLUSIONS: Most ALS patients receiving LTMV would want to stop it under certain circumstances, and the process of advance care planning enhances communication of patient preferences to family and physicians. Home-based LTMV is less costly and associated with greater patient satisfaction.

Quality of life and quality of care data from a 7-year pilot project for home ventilator patients.

A research demonstration pilot project for hospitalized adult and pediatric long-term ventilator-dependent patients was conducted by Kaiser Permanente Southern California Region from 1985 until 1992. The purpose of the pilot project was to investigate if home care was a realistic alternative to continued hospital care. Many aspects of home care as compared to hospital care were studied. The results of the quality of life and quality of care study in addition to cost data are presented in this paper. Standardized questionnaire tools were used to obtain patient data from the perspective of the patient, as well as others providing direct patient care. Respondents were asked to measure perceptions of quality of life and quality of care at home versus at the hospital in regard to health status, life satisfaction, emotional well-being, caregiver ability, and professional care and services. Quality of care was found to be similar to hospital care. Quality of life was judged to be better at home.

Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans.

Benign premature adrenarche (PA) is the term used to refer to girls with the early development of pubic hair before the age of 8 yr and is characterized by mild hyperandrogenism. Hyperandrogenism in adult women is often not as benign and has been associated with insulin resistance, acanthosis nigricans (AN), and the polycystic ovary syndrome. We have seen a group of young girls with PA who have also been found to have AN. The purpose of this study was to determine whether there are any clinical and biochemical differences in those girls with PA with and without AN. Twelve girls with PA were divided into two groups at the time of evaluation: group I, those without AN (n = 5); and group II, those with AN (n = 7). Adrenal androgen levels were determined in all subjects by a 60-min ACTH stimulation test. Insulin sensitivity was measured by the frequently sampled iv glucose tolerance test with tolbutamide and was assessed using the modified minimal model. Mean chronological age, bone age, and weight for length index were similar in the two groups. The baseline and stimulated levels of adrenal androgens were also not significantly different between the two groups. The group I girls (without AN) had an insulin sensitivity index of 6.75 +/- 1.31, which was in the normal prepubertal range. This was significantly different from that in group II (with AN), who had an insulin sensitivity index of 3.69 +/- 1.29. Therefore, many girls with premature adrenarche can have AN and decreased insulin sensitivity. Whether these girls have a truly benign course or are at risk of ovarian dysfunction or carbohydrate intolerance needs to be assessed.

Death and survival in a cohort of heroin addicts from London clinics: a 22-year follow-up study.

Data are presented on the 43 people who died over a 22-year follow-up period of a cohort of 128 heroin addicts drawn in 1969 from the newly opened London clinics. The main causes of death were drug-related, with 18 deaths specifically determined as due to overdose, of which the great majority were among people being prescribed opiates at the time. The mortality rate was a mean of 1.84% annually, and the excess mortality ratio was 11.9. This excess was highest at the beginning and varied over the period of study, appearing higher at the opening of the clinics and again in the mid-1980s. No sex differences in mortality rates were demonstrated but the excess mortality was concentrated at younger ages. No prediction of the 85 survivors could be made on the basis of length of heroin use prior to study intake, nor on age at intake.

Opiate users and the first years after treatment: outcome analysis of the proportion of follow up time spent in abstinence.

This second report on a follow-up study of drug users focuses on changes that occurred on a number of variables between intake and follow-up and during the follow-up period. The length of abstinence from opiates was considered as a proportion of the total follow-up period. Overall there was a reduction in opiate use, in injecting and sharing equipment at follow-up. There had been, however, a high level of these risky activities during the follow-up period. Sustained abstinence from opiates was associated with increased employment, enhanced social stability and mental health. Intake drug use was strongly related to follow-up drug status. In particular, those who were injectors of multiple drugs at intake were far less likely to be long term opiate abstainers at follow-up than those who were not injectors at intake or injectors of opiates only.

Thyrotropin-releasing hormone stimulation tests in infants.

The TSH response to TRH administration (7 micrograms/kg) was measured in 68 infants (22 premature) who had abnormal thyroid screening tests by the filter paper method and whose serum thyroid function tests were only mildly abnormal. Twenty-eight infants (12 premature) had peak TSH values of 35 mU/L or less and were considered normal (group I). Forty infants (10 premature) had peak TSH values above 35 mU/L and were considered hyperresponsive (group II). The mean age at testing, screening T4, TSH levels that prompted the testing, as well as baseline T4, T3, and free T4 at the time of TRH testing were not different between the groups. The mean (+/- SD) baseline TSH value was greater in group II (6.8 +/- 2.3 mU/L) than in group I (4.4 +/- 2.2 mU/L; P < 0.001). However, there was a great deal of overlap in the individual TSH values (group I, 0.9-10 mU/L; group II, 1.9-10.6 mU/L). Mean peak TSH levels were significantly different in the two groups (group I, 24 +/- 7.7 mU/L; group II, 60.3 +/- 26.1 mU/L; P < 0.001). During long term follow-up, all 25 group I infants available for evaluation have been confirmed as clinically and biochemically normal. No infant diagnosed as normal was later found to have evidence of hypothyroidism. Fourteen infants in group II have had evidence of thyroid dysfunction. We conclude that the TSH response to TRH stimulation is a useful tool for the evaluation of infants suspected of having primary hypothyroidism. Whether hyperresponsiveness to TRH represents a form of neonatal hypothyroidism requiring treatment remains to be determined.

Decision-making in the respiratory care of amyotrophic lateral sclerosis: should home mechanical ventilation be used?

As respiratory function starts to deteriorate in those with amyotrophic lateral sclerosis, one of the principal questions that has to be answered is whether it it is appropriate to provide ventilatory support. Although expensive, it is perfectly feasible to provide this at home, and this article examines many of the issues surrounding home mechanical ventilation.

X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies.

Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V2 vasopressin receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and NDI has been reported. In 1969, Bode and Crawford proposed, under the term "the Hopewell hypothesis," that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell early settlers, either by haplotype or by genealogical analysis. We confirm the locus homogeneity of the disease by linkage analysis in ethnically diverse families. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration.

Hearing the noise in the system. Exploration of textural analysis as a method for studying change in drinking behaviour.

This paper explores how treatment research is to catch within its design those many unplanned influences which lie outside therapeutic control, but which may influence processes of change. These factors are excluded from the conventional controlled trial. The background literature is briefly reviewed. A study is then described which employed a computer assisted method of textual analysis and an entirely open-ended coding system. The material which was analysed derived from interviews with 49 subjects whose accounts were tape recorded 10 years after treatment contact. Episodes of successful or unsuccessful 'change attempt' (CA) were identified. The two types of CA were compared in relation to coded issues pertaining to the periods before, during and after the episode. A number of significant findings are reported. In the pre-attempt phase 'Success' CAs were significantly associated with traumatic events in the person's life, and with a variety of positive and negative events. During the 'attempt' phase, 'Success' was associated with choice of an abstinence goal. For 'post-attempt', 'Success' was associated with 'Substitution', 'Altruism', 'Fulfillment', and finding the process 'Difficult'. The very preliminary nature of these findings is stressed and the need for further rigorous methodological development.

Alcohol and drug misuse among women--an overview.

Most research into substance misuse has focused on men but the problem among women is considerable and the social consequences and causation differ between the sexes. In the US, one-third of alcohol abusers are women and in the UK 1% of women are estimated to be drinking at a dangerous level. Drug and alcohol misuse holds additional problems for women since abusers tend to be of childbearing age. Rehabilitation units and prevention strategies would benefit more women substance abusers if they were tailored to suit their specific needs.

Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity.

EO-199, a specific antagonist of antiarrhythmic drugs: assessment by binding experiments and in vivo studies.

EO-199, a demethylated analog of the novel class I antiarrhythmic drug EO-122 was found to antagonize the antiarrhythmic activity of EO-122 and that of procainamide (Class IA). EO-199 did not block significantly the activity of a class IB antiarrhythmic agent, lidocaine. EO-199 also displaced the specific binding of [3H]EO-122 to rat heart membranes similarly to procainamide whereas lidocaine did not. The correlation between binding experiments and pharmacological effects points to a possible subclassification of these drugs; the two chemical analogs EO-199 and EO-122, as well as procainamide (IA) but not lidocaine (IB), compete at the same site or the same state of the sodium channel. The availability of a specific antagonist might be useful for studying the mechanism of action of antiarrhythmic drugs as well as an antidote in cases of antiarrhythmics overdose intoxication.

What happens to drug misusers? A medium-term follow-up of subjects new to treatment.

In a 2.5-5 year follow-up study of 150 drug misusers who were new to treatment at three London Drug Treatment agencies, a 77% follow-up rate was obtained. High rates of self-reported abstinence from opiates and other drugs were found. Some 37% of those followed-up were totally drug free at follow-up. Seventy-one per cent were living in the community and of those 73% were opiate free and 35% were totally drug free. Only 18% had injected in the 4 weeks prior to follow-up. Thirteen per cent were in prison and 12% were resident in a therapeutic community. Being told about the dangers of HIV had persuaded some people to give up using drugs.