Dependence on Hypnotic Drugs in General Practice

Of the patients in an industrial general practice 1.3% required hypnotic drugs regularly. They were predominantly in the older age groups (mean 62.7 years), with an excess of widows. Only 0.02% were severely dependent; the remainder were mildly so, though they had been taking hypnotics for long periods (mean 5.6 years). There were three main original indications for hypnotics—namely, medical (pain), psychiatric, and onset insomnia in anxious personality disorder. One-fifth of the patients first took hypnotics while in hospital. The group as a whole manifested a high degree of abnormal psychological disposition.It is suggested that many patients who take hypnotics regularly may be placebo reactors, and a more critical attitude to hypnotic prescribing is required both in hospital and in general practice.     

Benzodiazepine drugs in general medical patients.

Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.     

Sleep Apnea: A Prospective Study

Sleep apnea is remarkably prevalent among general medical patients. Of 26 men randomly selected on a Veterans Administratin hospital medical ward, with a mean age of 66.2 (SD=11.5) years, 7 (27%) had sleep apnea. Of concern is that two of the seven patients were receiving hypnotic drugs. Portable sleep recordings may need to be done when routinely assessing elderly medical patients.     

Effectiveness of geriatric rehabilitative care after fractures of the proximal femur in elderly women: a randomised clinical trial.

OBJECTIVE--To compare postoperative collaborative care between orthopaedic surgeons and physicians in geriatric medicine with routine orthopaedic care in elderly women with proximal femoral fracture. DESIGN--Exclusion of patients dying before fit enough to enter trial, those with pathological fractures, those likely to be discharged within seven days of entering the trial, and those remaining unfit for transfer to a peripheral hospital. Remainder allocated to two groups: treatment group and control group. SETTING--District hospital acute admission ward and rehabilitation ward. PATIENTS--144 sequentially admitted elderly women with proximal fracture of the femur; 36 excluded on above criteria and remainder entered into trial. INTERVENTION--Both treatment and control groups (n = 54 in each) received physiotherapy and other services. The treatment group also received thrice weekly supervision by a geriatrician. END POINTS--Physical independence, residence after discharge, and length of hospital stay. MEASUREMENTS AND MAIN RESULTS--At discharge significantly more patients in treatment group were independent in terms of activities of daily living than controls (41 v 25) and their median stay was 24 days (range 8-197) compared with 41 (9-365) (95% confidence intervals for difference 2 to 25). Significantly fewer treatment patients were discharged to institutional care (10% v 32%; 95% confidence interval for difference 6% to 37%) and more to their own homes (63% v 38%; 95% confidence interval for difference 6% to 44%). These beneficial effects were consistent across a range of ages and mental state. CONCLUSIONS--Both hospital and patient benefited when postoperative rehabilitation was provided in a setting specialising in such care for elderly patients with trauma.     

Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam.

The hypnotic and residual sedative effects of the first and seventh of seven regular night-time doses of nitrazepam 5 mg, temazepam 20 mg, and placebo were studied in 58 elderly inpatients. Plasma temazepam and nitrazepam concentrations rose by about 50% and 113% respectively between the mornings of day 1 and day 7. Patients reported sleeping well more often after the first dose of either hypnotic (p less than 0.05), but there was no difference after the seventh dose. Reaction time was unchanged on the morning after the first dose but was significantly prolonged after the seventh dose of both hypnotics (p less than 0.01). The time taken to eliminate the letter E from a page of prose tended to be prolonged after the first dose of both drugs (temazepam v placebo, p less than 0.05; nitrazepam v placebo, not significant) and was further prolonged on the morning after the seventh dose of nitrazepam (nitrazepam v placebo, p less than 0.05). Thus plasma accumulation of the drug was associated with a deterioration in daytime performance. This change in performance did not correlate with age, cerebral blood flow, or plasma concentration, but patients of low intelligence tended to be more severely affected.     

Hospital Physicians' Influence on Gastrointestinal Protection during Treatment with Non-Steroidal Anti-Inflammatory Drugs and Acetylsalicylic Acid and the Impact on Prescribing in Primary Care

Background

The aim of this study was to describe the use of gastrointestinal (GI) protection before, during and after hospitalisation for elderly patients using NSAID or low-dose ASA.

Methods

This study included all elderly patients (75+) admitted to hospital in the period of 1^st April 2010 to 31^st March 2011 at Odense University Hospital, Denmark, who were regular users of NSAID or low-dose ASA before hospital admission, or had one of these drugs initiated during hospital stay. By using pharmacy dispensing data and a hospital-based pharmacoepidemiological database, the treatment strategy for the individual patients was followed across hospital stay.

Results

In total, 3,587 patients were included. Before hospital admission, 93 of 245 NSAID users (38.0%) and 597 of 1994 user of low-dose ASA (29.9%) had used GI protection. During hospital stay, use of GI protection increased to 75% and 33.9%, respectively. When hospital physicians initiated new treatment with NSAID or with low-dose ASA, 305 of 555 (55.0%) and 647 of 961 (67.3%) were initiated without concomitant use of GI protection. When hospital physicians initiated GI protection, 26.8–51.0% were continued in primary care after discharge.

Conclusions

During hospital stay, the use of GI protection increases, but when new treatment with NSAIDs or low-dose ASA is initiated in hospital, the use of gastrointestinal protection is low. The low use of GI protection is carried on in primary care after discharge.     

Is an information booklet for patients leaving hospital helpful and useful?

OBJECTIVE--To determine whether a booklet given to patients being discharged from hospital giving details of their admission and treatment increased their knowledge and recall when reviewed in outpatient clinics. DESIGN--Patients alternately allocated to receive a booklet or to serve as controls. Assessment by a questionnaire at first attendance at outpatient clinic after discharge. Data were collected over nine months. SETTING--One general medical and cardiological ward in a large teaching hospital and associated outpatient clinics. PATIENTS--One hundred and thirty one patients discharged taking at least one drug and scheduled to return to clinic within 12 weeks. Patients stratified by age and by the number of weeks between discharge and outpatient appointment. INTERVENTION--A booklet was given to 65 patients at discharge from the ward; 66 patients served as controls. MAIN RESULTS--Of the patients who received the booklet, 56 (86%) knew the names of their drugs, 62 (95%) the frequency of the dose, and 55 (85%) the reasons for taking each drug. The numbers in the control group were 31 (47%), 38 (58%), and 28 (42%) respectively. These differences were highly significant (p less than 0.001). Twenty six (40%) who received the booklet brought all their drugs to clinic compared with 12 (18%) control patients. Appreciably more of the first group of patients than control patients knew the reason they had been in hospital, and more of the first group indicated that they would take the correct action when their prescribed drugs ran out. Most general practitioners thought that the booklet was a good idea, that it was helpful, and that it was better than the existing interim discharge letter. CONCLUSIONS--Giving patients an information booklet at discharge from hospital appreciably increased the accuracy and thoroughness of their recall of important medical details concerning their illness and its treatment. The booklet was shown to be feasible, helpful in the outpatient clinic, and preferred by most general practitioners.     

A comparative study of three hypnotics: methyprylon,glutethimide and chloral hydrate

A controlled study designed to evaluate the hypnotic potentiality of methyprylon (300 mg.), glutethimide (500 mg.) and chloral hydrate (1000 mg.) was carried out on 50 in-patients experiencing long-standing insomina. The patients ranged in age from 21 to 60 years, the sexes were equally represented and the clinical diagnoses were psychoneurosis, reactive depression, or anxiety reaction. An interesting feature of the experimental design allowed for the exclusion of placebo reactors before the initiation of the main trials. No difference in effectiveness of maintaining sleep could be established among the three hypnotic agents, indicating that at the usual levels of statistical significance, all three agents were equally effective as hypnotics. However, a significant trend (P = .05) was found for methyprylon (Noludar) to be the most effective and chloral hydrate to be the least effective of the three drugs in maintaining sleep. Methyprylon was found statistically (P = .05) to be the fastest sleep-inducing agent, whereas glutethimide (Doriden) proved to be the slowest of the three hypnotics with respect to sleep induction time.     

The effect of previous administration of adrenaline or isoprenaline on the activity of several hypnotics in mice]

Previous administration of adrenaline (0.5 mg/kg i.p.) and isoprenaline (10 mg/kg i.p.) enhances activity of several hypnotic drugs (pentobarbital, barbital, chloral hydrate) in mice but is without effect upon hypnotic activity of ethanol. This potentialisation is blocked by previous administration of pindolol, but not by phentolamine. Administration of SKF 525 A demonstrates that metabolism of pentobarbital is modified by this enzymatic inhibitor, which is not the case for other hypnotics.     

Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs

A genotoxic effect for antineoplastic drugs, in particular micronucleus induction, has been shown in several studies. The aim of our study was to assess genotoxic effects in nurses administering different mixtures of antineoplastic drugs in an oncology hospital by evaluating the frequency of micronuclei in exfoliated buccal cells and blood lymphocytes by use of the standard micronucleus (MN) test and by identifying, by means of FISH analysis with centromeric probes, the mechanism of micronucleus induction (clastogenic or aneugenic). The study group comprised 23 nurses, 10 of whom worked in the day-care hospital and 13 in the ward. Twenty healthy subjects were selected as controls. Pan-centromeric FISH analysis was performed on lymphocytes from a selected group of nurses (12/23 subjects) characterized by higher MN frequencies as observed by standard Giemsa staining. A significant increase of micronucleus frequency compared with controls was found in exfoliated buccal cells of both groups of nurses: day-care hospital nurses 0.92 versus 0.45 (p=0.034) and ward nurses 0.94 versus 0.45 (p=0.051). An increase, although not statistically significant, of mean MN frequency was also found by the MN standard test on lymphocytes of the day-care hospital nurses (10.9 versus 7.5; p=0.056), while no differences were found in ward nurses (8.15 versus 7.5; p=0.56). We found that the administration of antineoplastic drugs by nurses in ward units induced a higher frequency of FISH MN+ (43% of subjects) than in the day-care hospital (20%). This was associated with the micronucleus size percentage. This finding could be correlated with the different compositions of administered mixtures of antineoplastic drugs: in ward units the mixtures contained drugs, such as vinorelbine, that were absent in the mixtures administered in the day-care hospital. Our results show genetic damage induced by administration of antineoplastic drugs, particularly in exfoliated buccal cells. This result suggests the useful application of this non-invasive sampling to evaluate genotoxic effects of occupational exposure to mixtures of inhalable chemicals at low doses.     

Prevalence,frequency, and duration of hypnotic drug use among the elderly living at home

Details of consumption of hypnotic drugs derived from a nationally representative sample of elderly people were analysed in terms of the prevalence, duration, and likely frequency of use. Of 1020 randomly selected subjects aged 65 and over 16% (166) reported using (mainly benzodiazepine) hypnotic drugs, and of these 89% reported having taken such a drug the night before the interview. Most of these users (73%) had been taking hypnotic drugs for more than one year, with 25% reporting drug use for more than 10 years.These results suggest that for most elderly users of hypnotic drugs, patterns of consumption encourage the development of cumulative effects and benzodiazepine dependence.     

前列腺切除术围术期出血与临床护理预处理的关系

研究护理中术前服用度他雄胺2周减少前列腺内二氢睾酮和前列腺组织血管分布对前列腺术后出血的影响。本研究纳入了83例符合TURP适应症的良性前列腺增生患者。度他雄胺组由40名患者组成,术前两周内接受度他雄胺(0.5 mg/d)治疗;对照组由43名患者组成,术前两周内不接受度他雄胺治疗。根据术前、术后、术后24 h的血清血红蛋白(Hb)和血细胞比容(Hct)水平来评估失血情况。本次研究还探究了药物对留置尿道导管的使用时间、连续盐水膀胱冲洗时间和住院时间的影响。术后和术后1 d平均失血量方面,度他雄胺组低于对照组(ΔHb=(0.65±1.27) g/d L∶(1.16±0.73) g/d L,(1.30±1.00) g/dL∶(1.86±1.05) g/dL,p=0.019,p=0.011;ΔHct=(1.89±3.83)%∶(3.47±2.09)%,(3.69±2.95)%∶(5.39±3.23)%,p=0.016,p=0.011)。此外,在度他雄胺组中,尿道留置导尿管天数((2.95±1.02) d∶(3.92±1.14) d,p=0.000)、连续盐水膀胱冲洗时间((1.81±1.08) d∶(2.36±1.06) d,p=0.016)和TURP后的住院时间((3.95±1.09) d∶(4.76±1.19) d,p=0.001)较小。本研究表明,在TURP术前护理中用度他雄胺进行两周的治疗,可减少术后出血和TURP术后住院时间。这种临床护理预处理可用于减少与TURP相关的手术出血,建议临床使用。     

Adverse Drug Reactions in Hospitalised Children in Germany Are Decreasing: Results of a Nine Year Cohort-Based Comparison

Background

In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period.

Methodology

Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis.

Results

A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001).

Conclusions

Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed.     

Acute drug poisoning in the adult

In a prospective study of 349 patients with acute poisoning treated at The Montreal General Hospital in 1972 benzodiazepines and non-barbiturate hypnotics were found to be the most frequent putative drugs. Of the 108 patients admitted to hospital 37% had taken an overdose of a drug prescribed for them by their psychiatrist or other physician; 48% had formerly taken an overdose of drugs and 44% had had previous psychiatric treatment. Unconsciousness, respiratory depression, metabolic acidosis and acidemia, and hypokalemia were the most frequent clinical abnormalities observed. Treatment was supportive. There were six deaths. The average duration of coma was short; only five surviving patients remained unconscious for more than 24 hours. Respiratory complications were frequent.It is recommended that more attention be paid to recognizing patients whose behaviour pattern might include such an impulsive gesture, and that alternatives be found for barbiturate and non-barbiturate hypnotics.     

Evaluating the effectiveness of a process medical audit in a teaching general hospital.

Medical auditing has moved beyond the traditional chart review to the process audit, which identifies deficiencies in care and suggests remedies. In 1981 the audit committee of the Department of Psychiatry at Toronto General Hospital audited the use of hypnotic drugs in the inpatient unit. The audit produced two recommendations: that nursing staff record sleep graphs for inpatients more often, and that an educational program be instituted to change the physicians'' patterns of prescribing hypnotics. In 1983 the audit was repeated to test the effectiveness of the 1981 auditing process. The 1981 recommendation produced the desired improvement in recording of sleep graphs. However, the medical staff failed to change their patterns of prescribing hypnotics: oxazepam remained the preferred hypnotic. For the process audit to be effective in improving patient care those using it must ensure that the methods reflect the nature and structure of the professional group they are trying to influence.     

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

BackgroundBenzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.Methods and findingsThe retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score–stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.ConclusionsIn US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine–opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

In a retrospective cohort study, Dr. Wayne Ray and colleagues investigate concurrent opioid and hypnotic use and mortality in older adults in US.     

Inappropriate hospital use by patients receiving care for medical conditions: targeting utilization review

OBJECTIVE: To describe characteristics associated with inappropriate hospital use by patients in Manitoba in order to help target concurrent utilization review. Utilization review was developed to reduce inappropriate hospital use but can be a very resource-intensive process. DESIGN: Retrospective chart review of a sample of adult patients who received care for medical conditions in a sample of Manitoba hospitals during the fiscal year 1993-94; assessment of patients at admission and for each day of stay with the use of a standardized set of objective, nondiagnosis-based criteria (InterQual). PATIENTS: A total of 3904 patients receiving care at 26 hospitals. OUTCOME MEASURES: Acute (appropriate) and nonacute (inappropriate) admissions and days of stay for adult patients receiving care for medical conditions. RESULTS: After 1 week, 53.2% of patients assessed as needing acute care at admission no longer required acute care. Patients 75 years of age or older consumed more than 50% of the days of stay, and 74.8% of these days of stay were inappropriate. Four diagnostic categories accounted for almost 60% of admissions and days, and more than 50% of those days of stay were inappropriate. Patients admitted through the emergency department were more likely to require acute care (60.9%) than others (41.7%). Patients who were Treaty Indians had a higher proportion of days of stay requiring acute care than others (45.9% v. 32.8%). Patients'' income and day of the week on admission (weekday v. weekend) were not predictive factors of inappropriate use. CONCLUSION: Rather than conducting a utilization review for every patient, hospitals might garner more information by targeting patients receiving care for medical conditions with stays longer than 1 week, patients with nervous system, circulatory, respiratory or digestive diagnoses, elderly patients and patients not admitted through the emergency department.     

Intensive Hospital Monitoring of Adverse Reactions to Drugs

A total of 1,268 patients admitted to hospital wards were kept under surveillance by one observer throughout their stay in hospital. All drugs given to them and the occurrence of adverse reactions were recorded.Drug reactions were found in 10·2% of the 1,160 patients who received drug therapy. Most reactions were due to known pharmacological actions of the drugs. Though only four reactions were of life-threatening seriousness, 80% of the 129 reactions observed were of moderate severity. Digitalis preparations, bronchodilator drugs, and ampicillin had the highest reaction rates. It is suggested that larger surveys of adverse reactions in relation to drug usage would make a useful contribution to the problem.     

Patients' and general practitioners' satisfaction with information given on discharge from hospital: audit of a new information card.

OBJECTIVE--To determine the attitudes of patients discharged from hospital and their general practitioners to a new information card giving details about admission, diagnosis, and treatment and to assess the completeness of the information on the card. DESIGN--Consecutive patients discharged from the care of three consultant physicians over 16 weeks. SETTING--One general medical ward in a large teaching hospital. PATIENTS--A total of 275 consecutive discharges of 258 patients were studied. The mean age of patients was 60 years and mean duration of admission five days. INTERVENTION--At discharge from the ward all study patients received an information card and a copy of the card in the form of an interim discharge letter to be delivered to their general practitioner. Patients and general practitioners were asked to complete a questionnaire giving their views on the legibility, helpfulness, quality, and quantity of the information they received. Copies of all the information cards were scrutinised for completeness. MAIN RESULTS--The results were based on 208 (76%) forms returned by patients and 214 (78%) forms returned by general practitioners. Information was considered very helpful or quite helpful according to 170 (83%) forms from patients and 197 (92%) forms from general practitioners; sufficient information was provided according to 160 and 182 forms. Most patients and nearly all general practitioners thought it was a good idea to provide this information for patients at discharge. According to 125 forms from patients and 188 from general practitioners the information card was very easy or quite easy to read; 155 patients had read it at least twice and 149 were likely to refer to it again. OTHER RESULTS--The written information about the patient, the diagnosis, and what the patient had been told was generally well completed, although the date of discharge was omitted from 42 (15%) cards. Details of drugs prescribed at discharge were generally thorough. CONCLUSIONS--Giving an information card to all patients at discharge was feasible and favoured by most patients and their general practitioners. Having made minor changes in design, we think that we have produced an information card that is a convenient size and will improve communication between patients, their general practitioners, and hospital doctors. We now issue this card routinely to all patients discharged from our ward and hope that it might be widely adopted.