Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care

Rationale

Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities.

Methods

We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug prescribing and neuropsychiatric co-morbidities of 0–24 year olds between 1992 and 2008.

Results

ASD prevalence increased 65-fold from 0.01 % (1992) to 0.50 % (2008). Psychotropic drugs were prescribed to 29 % (1,619/5,651) of the ASD cohort; the most prescribed drugs were sleep medication (9.7 % of prescribed patients), psychostimulants (7.9 %) and antipsychotics (7.3 %). More patients were given psychostimulants and sleep medications over time from 1.5–6.3 % and 2.2–5.9 % respectively. Thirty-seven per cent of the cohort had ≥1 record of a neuropsychiatric co-morbidity, the most common being developmental difficulties and learning disabilities (12.6 %), behavioural, conduct and personality disorders (11.1 %) and attention deficit hyperactivity disorder (7.5 %).

Conclusions

British physicians are more conservative in prescribing practice than American colleagues. However, use of psychostimulants and antipsychotics is much higher in those with ASD than in the general population. Polypharmacy was seen in 34 % of prescribed patients in 2008. Additional studies examining use, efficacy, and long-term safety of antipsychotics and psychostimulants in autistic individuals are warranted.     

Drug-induced life-threatening potassium disturbances detected by a pharmacovigilance program from laboratory signals

Purpose

Detection and reporting of drug-induced life-threatening potassium disturbances and the study of associated factors under a Pharmacovigilance Program using Laboratory Signals at a Hospital (PPLSH) during a 2-year period.

Methods

All serum potassium levels <2 mmol/l or >7 mmol/l detected at admission to the hospital, including those of patients who died in the emergency ward or during hospitalization, were monitored prospectively from January 2009 through to December 2010. The incidence rate of each etiology of potassium disturbances was calculated. Factors associated with drug-induced potassium disturbances were detected using a multiple logistic regression model.

Results

The incidence of true life-threatening drug-induced hyper- and hypokalemia events was 3 and 4.32 (Poisson 95 % confidence interval 1.62–10.24), respectively, per 10,000 admissions. Of the severe potassium disturbances, 32.3 % were drug-induced, and 23 % were lethal. We identified previously undescribed pharmacological causes of hyperkalemia (risedronate, doxazosin) and hypokalemia (acyclovir, teicoplanin, cefepime, meropenem, dexketoprofen colistimethate). Significant predictor factors associated with drug-induced hyperkalemia were the use of polypharmacy (>5 drugs), age (>74 years), sex (female) and kidney disease (glomerular filtration rate <60 ml/min) with the presence of ≥4 comorbid conditions. The only predictor of drug-induced hypokalemia was the use of >5 drugs. The triggering factor associated with drug-induced hyperkalemia and hypokalemia was azotemia and hypoalbuminemia, respectively.

Conclusions

Drug-induced life-threatening potassium disturbances remain a relevant problem. Potential strategies for prevention are to avoid polypharmacy, early discontinuation of treatment of drugs causing hyperkalemia or nephrotoxicity in cases of various clinical situations (cardiac descompensation, infection, hypovolemia) or obstructive causes, and insistence on albumin control during hospitalization.     

Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study

Purpose

Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations.

Methods

We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines.

Results

A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma.

Conclusions

Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem.     

Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations

Aim and background

To assess drug-related problems in patients with liver cirrhosis by investigating the prevalence of inadequately dosed drugs and their association with adverse drug reactions (ADRs) and hospitalizations.

Methods

This was a cross-sectional retrospective study assessing the dose adequacy of drug treatment of 400 cirrhotic patients at hospital admission based on the authors’ own previous studies and standard literature. The prevalence of total and preventable ADRs and of hospitalizations due to preventable ADRs was determined.

Results

Of all 1653 drugs prescribed (median 4 per patient), 336 (20 %) drugs were inadequately dosed in 184 patients. Overall, 210 ADRs (78 % preventable) occurred in 120 patients. Sixty-nine ADRs (33 % of all ADRs) were associated with inadequate drug dosing in 46 patients, of which 68 % were preventable. Nonsteroidal anti-inflammatory drugs and psycholeptics in particular frequently caused preventable ADRs associated with inadequate drug dosing. Inadequate drug dosing was more frequently associated with ADRs than adequate drug dosing, and patients receiving inadequately dosed drugs were more frequently admitted to the hospital due to ADRs. Hospitalization of patients receiving inadequately dosed drugs that caused preventable ADRs resulted in 94 additional hospital days.

Conclusion

In this retrospective study, inadequate drug dosing was associated with an increased frequency of ADRs, hospital admissions and hospital days in cirrhotic patients. We therefore conclude that the careful dosing of critical drugs is important in patients with liver cirrhosis.     

Polypharmacy, length of hospital stay, and in-hospital mortality among elderly patients in internal medicine wards. The REPOSI study

Purposes

We evaluated the prevalence and factors associated with polypharmacy and investigated the role of polypharmacy as a predictor of length of hospital stay and in-hospital mortality.

Methods

Thirty-eight internal medicine wards in Italy participated in the Registro Politerapie SIMI (REPOSI) study during 2008. One thousand three hundred and thirty-two in-patients aged ??65?years were enrolled. Polypharmacy was defined as the concomitant use of five or more medications. Linear regression analyses were used to evaluate predictors of length of hospital stay and logistic regression models for predictors of in-hospital mortality. Age, sex, Charlson comorbidity index, polypharmacy, and number of in-hospital clinical adverse events (AEs) were used as possible confounders.

Results

The prevalence of polypharmacy was 51.9% at hospital admission and 67.0% at discharge. Age, number of drugs at admission, hypertension, ischemic heart disease, heart failure, and chronic obstructive pulmonary disease were independently associated with polypharmacy at discharge. In multivariate analysis, the occurrence of at least one AE while in hospital was the only predictor of prolonged hospitalization (each new AE prolonged hospital stay by 3.57?days, p?p?=?0.02), comorbidities (OR 1.18; 95% CI 1.12?C1.24; p?p?Conclusions Although most elderly in-patients receive polypharmacy, in this study, it was not associated with any hospital outcome. However, AEs were strongly correlated with a longer hospital stay and higher mortality risk.     

Different patterns in use of antibiotics for lower urinary tract infection in institutionalized and home-dwelling elderly: a register-based study

Purpose

We compared the quality and pattern of use of antibiotics to treat urinary tract infection (UTI) between institutionalized and home-dwelling elderly.

Methods

We analyzed the quality of use of UTI antibiotics in Swedish people aged ≥65 years at 30 September 2008 (1,260,843 home-dwelling and 86,721 institutionalized elderly). Data regarding drug use, age and sex were retrieved from the Swedish Prescribed Drug Register and information about type of housing from the Social Services Register. In women, we assessed: (1) the proportion who use quinolones (should be as low as possible); (2) the proportion treated with the recommended drugs (pivmecillinam, nitrofurantoin, or trimethoprim) (proportions should be about 40 %, 40 % and 15–20 %, respectively); In men, we assessed: (1) the proportion who used quinolones or trimethoprim (should be as high as possible).

Results

The 1-day point prevalence for antibiotic use for UTI was 1.6 % among institutionalized and 0.9 % among home-dwelling elderly. Of these, about 15 % of institutionalized and 19 % of home-dwelling women used quinolones. The proportion of women treated with the recommended drugs pivmecillinam, nitrofurantoin or trimethoprim was 29 %, 27 % and 45 % in institutions and 40 %, 28 % and 34 % for home-dwellers. In men treated with antibiotics for UTI, quinolones or trimethoprim were used by about 76 % in institutions and 85 % in home-dwellers.

Conclusions

Our results indicate that recommendations for UTI treatment with antibiotics are not adequately followed. The high use of trimethoprim amongst institutionalized women and the low use of quinolones or trimethoprim among institutionalized men need further investigation.     

Statin use among older Finns stratified according to cardiovascular risk

Purpose

Statin use has increased in older age groups, although there is little evidence for the benefits of statin therapy in the elderly, especially in low-risk persons. The aim of this paper is to describe recent trends in the prevalence and incidence of statin use among the Finnish older population, according to the person’s estimated cardiovascular (CV) event risk.

Methods

We conducted a register study covering the whole community-dwelling population of Finland, aged >70 years in 2000–2008 (N?=?883,051). Data on reimbursed purchases of statins, antidiabetic and CV drugs, and pre-existing CV diseases were retrieved from comprehensive national registers. We stratified each person into low, moderate or high CV risk category, and according to age (70–74, 75–79, and >80 years) and sex.

Results

Between 2000 and 2008, the age-sex-standardized prevalence of statin use tripled from 12.2 % to 38.7 % (rate ratio 3.0, 95 % CI 3.0–3.1), and the incidence almost doubled (from 3.7 % to 6.8 %; rate ratio 1.8, 95 % CI 1.8–1.9). The prevalence and incidence of statin use were consistently highest among high-risk persons. The greatest relative increases were observed in persons aged >80 years and in those at low risk; however, the proportion of statin users at low CV risk remained the same (～7 % of all users).

Conclusions

Statin prescribing is shifting towards older age groups. A substantial increase in prevalence and incidence was seen across all risk categories, but the channeling of statin use towards high-risk persons remained unchanged.