Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence

<p>Abstract</p> <p>Background</p> <p>In order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS) in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed.</p> <p>Methods</p> <p>Patients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS) containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands.</p> <p>The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed.</p> <p>Results</p> <p>The transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period.</p> <p>The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51%) of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%), cumulative medication gaps (1–8 years 69.1%) and discontinuing (23.2%) during ten-year follow-up for new users. New users had lower probability of continuous use (7.7%) and more variability in ICS refill patterns than previous users (56%).</p> <p>Conclusion</p> <p>In addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in behaviour and patterns of ICS use and could also be useful to investigate continuous use of other drugs applied in chronic diseases.</p

Assessment of pediatric asthma drug use in three European countries; a TEDDY study.

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ß2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ß2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ß2-mimetics (the UK highest). Off-label use was low, and most pronounced for ß2-mimetics in children <18 months (IT) and combined ß2-mimetics + anticholinergics in children <6 years (NL). CONCLUSION: This study shows that among all asthma drugs, ß2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety

Comparing the transcriptomes of embryos from domesticated and wild Atlantic salmon (Salmo salar L.) stocks and examining factors that influence heritability of gene expression

Background&nbsp; Due to selective breeding, domesticated and wild Atlantic salmon are genetically diverged, which raises concerns about farmed escapees having the potential to alter the genetic composition of wild populations and thereby disrupting local adaptation. Documenting transcriptional differences between wild and domesticated stocks under controlled conditions is one way to explore the consequences of domestication and selection. We compared the transcriptomes of wild and domesticated Atlantic salmon embryos, by using a custom 44k oligonucleotide microarray to identify perturbed gene pathways between the two stocks, and to document the inheritance patterns of differentially-expressed genes by examining gene expression in their reciprocal hybrids.&nbsp; Results&nbsp; Data from 24 array interrogations were analysed: four reciprocal cross types (W♀&times;W♂, D♀&times;W♂; W♀&times;D♂, D♀&times;D♂)&times;six biological replicates. A common set of 31,491 features on the microarrays passed quality control, of which about 62% were assigned a KEGG Orthology number. A total of 6037 distinct genes were identified for gene-set enrichment/pathway analysis. The most highly enriched functional groups that were perturbed between the two stocks were cellular signalling and immune system, ribosome and RNA transport, and focal adhesion and gap junction pathways, relating to cell communication and cell adhesion molecules. Most transcripts that were differentially expressed between the stocks were governed by additive gene interaction (33 to 42%). Maternal dominance and over-dominance were also prevalent modes of inheritance, with no convincing evidence for a stock effect.&nbsp; Conclusions&nbsp; Our data indicate that even at this relatively early developmental stage, transcriptional differences exist between the two stocks and affect pathways that are relevant to wild versus domesticated environments. Many of the identified differentially perturbed pathways are involved in organogenesis, which is expected to be an active process at the eyed egg stage. The dominant effects are more largely due to the maternal line than to the origin of the stock. This finding is particularly relevant in the context of potential introgression between farmed and wild fish, since female escapees tend to have a higher spawning success rate compared to males

The use of electronic alerts in primary care computer systems to identify the excessive prescription of short-acting beta2-agonists for people with asthma: a systematic review.

Computers are increasingly used to improve prescribing decisions in the management of long-term conditions however the effects on asthma prescribing remain unclear. We aimed to synthesise the evidence for the use of computerised alerts that identify excessive prescribing of short-acting beta2-agonists (SABAs) to improve asthma management for people with asthma. MEDLINE, CINAHL, Embase, Cochrane and Scopus databases (1990-2016) were searched for randomised controlled trials using electronic alerts to identify excessive prescribing of SABAs for people with asthma in primary care. Inclusion eligibility, quality appraisal (Cochrane risk of bias tool) and data extraction were performed by two independent reviewers. Findings were synthesised narratively. A total of 2035 articles were screened and four trials were eligible. Three studies had low risk of bias: one reported a positive effect on our primary outcome of interest, excessive SABA prescribing; another reported positive effects on the ratio of inhaled corticosteroid (ICS)-SABA prescribing, and asthma control; a third reported no effect on outcomes of interest. One study at high risk of bias reported a reduction in exacerbations and primary care consultations. There is some evidence that electronic alerts reduce excessive prescribing of SABAs, when delivered as part of a multicomponent intervention in an integrated health care system. However due to the variation in health care systems, intervention design and outcomes measured, further research is required to establish optimal design of alerting and intervening systems.The authors wish to thank Asthma UK and Queen Mary University London for funding this work as part of a PhD studentship carried out by S.M. A.D.S. is funded by a NIHR Academic Clinical Lectureship. A.B. is a National Institute for Health Research (NIHR) Senior Investigator and additionally was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. M.T. is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Wessex, NIHR School of Primary Care Research and NIHR Southampton Biomedical Research Centre. C.G. is supported by the NIHR CLAHRC North Thames at Bart’s Health NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This work is funded by Asthma UK and Queen Mary University of London

Pediatric DXA: clinical applications

Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation

Ensaio clínico, aberto, controlado sobre a adição de brometo de ipratrópio ao fenoterol no tratamento da crise de asma em adultos Open, controlled clinical assay of the addition of ipratropium bromide to fenoterol in the treatment of acute asthma crisis in adults

No tratamento da crise de asma, empregam-se doses repetidas de drogas b2-agonistas por via inalatória. O efeito da adição do brometo de ipratrópio (BI) ao b2-agonistas é controverso em adultos. OBJETIVO: Avaliar se adição de BI ao fenoterol, em tratamentos inalatórios repetidos, induz a maior broncodilatação, com reversibilidade da crise e alta da emergência em pacientes em crise grave de asma. LOCAL DO ESTUDO: Serviço de Pronto-Atendimento de Pneumologia, Disciplina de Pneumologia da Unifesp-Hospital São Paulo, no período de julho de 1995 a fevereiro de 1997. TIPO DE ESTUDO: Aberto, randomizado, paralelo. Alta da emergência determinada pelo VEF1 e PFE > 60% do previsto. CASUÍSTICA E MÉTODOS: Cento e vinte pacientes em crise de asma foram divididos em dois grupos (N = 60): fenoterol (F) e brometo de ipratrópio + fenoterol (BIF) com VEF1 e PFE < 50% do previsto. Cada grupo recebeu três tratamentos inalatórios, através de nebulímetro e câmara de expansão, administrados em intervalos de 30 minutos. No grupo F foram administrados 4 jatos de fenoterol (400mcg) e no grupo BIF, 160mcg de BI e 400mcg de fenoterol (4 jatos). RESULTADOS: A média (± DP) do PFE basal (F = 36 ± 7% vs. BIF = 35 ± 9% previsto) e do VEF1 basal (F = 33 ± 9% vs. BIF = 32 ± 9%). Trinta e dois pacientes no grupo F e 33 pacientes no grupo BIF tiveram alta após tratamentos inalatórios. O VEF1 e PFE ao final dos tratamentos inalatórios foram, respectivamente, F = 60 ± 13% vs. BIF = 61 ± 11% e F = 74 ± 18% vs. BIF = 77 ± 13% (NS). CONCLUSÃO: A adição de brometo de ipratrópio ao fenoterol resulta em efeito funcional insignificante e sem impacto clínico no tratamento da crise de asma em adultos.<br>Repeated dosis of inhaled b2-agonists have been used in the treatment of acute asthma. The effect of added ipratropium bromide (IB) to b2-agonist is controversial in adults. OBJECTIVE: To evaluate if addition of IB to fenoterol, in repeated doses, induces a greater bronchodilation, a greater reversion of the attack, and discharge from emergency unit in adults with acute severe asthma. SETTING: Pneumology Emergency Department, Unifesp-Hospital São Paulo, in the period from July 1995 to February 1997. TYPE OF STUDY: Open, randomized and parallel study. Discharge from the hospital: FEV1 and PEF > 60% of the predicted value. METHODS: 120 patients with FEV1 and PEF < 50% of the predicted value were divided into two groups (N = 60): fenoterol (F) and ipratropium bromide + fenoterol (IBF). Each group received inhalation treatment through a metered-dose inhaler (MDI) attached to a holding chamber, administered at 30-minute interval, for a total of three treatments. In the group F four puffs of fenoterol (400 mg) were administered, and in the IBF group, 160 mg of BI and 400 mg of fenoterol (four puffs). RESULTS: The patients did not differ from basal PEF (F = 36 ± 7% vs IBF = 35 ± 9% predicted) and basal FEV1 (F = 33 ± 9% vs IBF = 32 ± 9% predicted). Thirty-two patients of group F and 33 of group IBF were discharged from hospital after the inhalation treatment. The final FEV1 and PEF after inhalation treatments were F = 60 ± 13% vs IBF = 61 ± 11% e F = 74 ± 18% vs IBF = 77 ± 13% (NS). CONCLUSION: The addition of ipratropium bromide to fenoterol results in insignificant functional effect and without clinical impact in the treatment of acute asthma in adults

Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study

BACKGROUND: Patients using higher dosages of inhaled or oral glucocorticoids (GCs) have an increased risk of hip/femur fractures. The role of the underlying disease in the aetiology of this increased risk has not been widely studied. OBJECTIVE: To evaluate the contribution of the underlying disease to the risk of hip/femur fracture in patients using inhaled or oral GCs. DESIGN AND SUBJECTS: A case-control study within the Dutch PHARMO-RLS database was conducted. Cases (n = 6763) were adult patients with a first hip/femur fracture during enrolment. Each case was matched to four controls by age, gender and region. RESULTS: The risk of hip/femur fracture increased with current use of inhaled GCs (crude OR 1.30, 95% CI:1.16-1.47) and with current use of oral GCs (crude OR 1.66, 95% CI: 1.46-1.90). After adjustment for disease severity, the risk of hip/femur fracture was no longer statistically significantly increased in inhaled GC users (adjusted OR 1.08, 95% CI: 0.91-1.27), whilst it remained elevated in oral GC users (adjusted OR 1.43, 95% CI: 1.22-1.67). Patients using inhaled GCs without any exposure to oral GCs had no increased risk of fracture (adjusted OR 0.98, 95% CI: 0.79-1.22). CONCLUSION: Inhaled GC users had no increased risk of femur/hip fracture after adjustment for underlying disease severity. Our data suggest that, even at higher dosages, inhaled GC use is not an independent risk factor for fracture. In contrast, oral GC use was associated with an increased risk of fracture, which was not fully explained by the underlying disease severity