Multi-dose drug dispensing and inappropriate drug use: A nationwide register-based study of over 700,000 elderly

Objective

To investigate whether the use of multi-dose drug dispensing is associated with potentially inappropriate drug use (IDU).

Design

Cross-sectional nationwide register-based study.

Setting

Sweden.

Subjects

People aged ≥75 years registered in the Swedish Prescribed Drug Register during October–December 2005.

Main outcome measures

Potentially IDU, i.e. anticholinergic drugs, long-acting benzodiazepines, concurrent use of three or more psychotropic drugs, and combinations of drugs that may lead to potentially serious drug–drug interactions (DDIs).

Results

After adjustment for age and number of dispensed drugs, any IDU, anticholinergic drugs, and three or more psychotropic drugs were associated with multi-dose drug dispensing, whereas the opposite relationship prevailed for long-acting benzodiazepines among women and potentially serious DDIs in both men and women. Among the subjects aged 75–79 years, multi-dose drug dispensing was even more strongly associated with any IDU, anticholinergic drugs, three or more psychotropic drugs in both men and women, and long-acting benzodiazepines among men.

Conclusion

Our results indicate that multi-dose users may be more exposed to potential IDU. However, multi-dose users seem to have a lower probability of potentially serious DDIs. Future research on multi-dose drug dispensing is necessary to ensure a high quality of drug therapy within this system.     

盐酸氨基葡萄糖联合塞来昔布治疗膝骨性关节炎的随机对照

背景：盐酸氨基葡萄糖被认为具有治疗膝关节骨性关节炎的作用,但其是否对不同程度的骨性关节炎都有效,联合应用非类固醇类抗炎药与单用盐酸氨基葡萄糖是否存在疗效差别,尚需进一步临床研究。目的：采用前瞻性研究的方法对比单用盐酸氨基葡萄糖以及联合应用塞来昔布治疗不同程度膝关节骨性关节炎的临床疗效。方法：采用Lequesne评分将152例膝关节骨关节炎患者分为轻、中、重度,然后随机配比法均分为单用盐酸氨基葡萄糖组和盐酸氨基葡萄糖联合塞来昔布用药组,于用药后2,4,6周以及停药8,12周统计患者Lequesne评分,用药前后及组间进行对比并统计盐酸氨基葡萄糖的不良反应。结果与结论：在轻度骨性关节炎治疗组中,盐酸氨基葡萄糖组治疗4周、停药12周后Lequesne评分与治疗前比较,差异有显著性意义;而联合用药组治疗2周后评分即有改善,两组比较,评分在治疗2,4周差异有显著性意义,说明联合用药组效果改善更显著;中度骨性关节炎患者在治疗2,4,6周和停药8周时,联合用药患者Lequesne评分均低于单纯使用盐酸氨基葡萄糖患者,差异均有显著性意义(P<0.05),说明在中度骨性关节炎,盐酸氨基葡萄糖联合塞来昔布治疗效果好于单独用药;重度骨性关节炎中,两组治疗后Lequesne评分与治疗前比较,均无明显改善。结果说明对于轻度膝骨性关节炎,单用盐酸氨基葡萄糖口服即可明显改善患者临床症状,对于中度膝骨关节炎,建议联合非类固醇类抗炎药类用药,可以较好改善临床症状,而对于重度膝骨关节炎,两种方法均无效。     

Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems

Several non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with liver damage. The aim of this study was to compare proportions of hepatic adverse drug reaction reports associated with NSAIDs in France and Spain. Information from the Spanish and French pharmacovigilance databases were used from 1982 to 2001. To assess the risk of liver injury, the case/non-case methodology was applied, 'cases' being reports of liver damage and 'non-cases' or controls, all other reports. Exposure was considered as the presence of at least one NSAID. Liver injury risk was estimated for each drug in the two databases by calculation of reporting odds ratio in cases and non-cases, with its 95% confidence interval. Out of 62 456 reports from the Spanish database, 2114 (3.38%) were identified as liver injuries, whereas there were 27 372 liver injuries out of 200 046 (13.68%) in the French database. In Spain, there was a significant association between liver injuries and droxicam, sulindac, and nimesulide. The risk was also slightly above 1 for aceclofenac. In France, the risk was very high with clometacin, followed by sulindac, and was slightly above 1 for naproxen, diclofenac, piroxicam, and tenoxicam. This study shows that some NSAIDs are associated with reports of hepatic injuries when compared with other drugs, and most of those have been withdrawn from the market for this reason. However, the frequency of drug-related hepatic injuries reported differed in the French and Spanish databases, and some drugs did not show the same risk level in the two countries. These discrepancies could be explained in part not only by reporting rates, but also by difference in drug use patterns and/or by genetic or environmental factors.     

A randomized, double-blind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children

Summary— Two hundred and nineteen children (boys: 56%, girls: 44%) were included in a randomized, double-blind, multicentre (4 centres) controlled trial designed to assess the efficacy and safety of ibuprofen (IBU) in the treatment of 1 to 6 year-old children with otoscopically proven acute otitis media (AOM), either unilateral or bilateral. They randomly received 10 mg/kg IBU (n = 71), or acetaminophen (PARA) (n = 73) or placebo (PLA) (n = 75), orally, tid, for 48 hours. All received oral cefaclor (Alfatil®, Lilly, France) for seven days. They were evaluated before (D0) and at the end of treatment (D2). The main criterion of response was the aspect (landmarks and color) of the tympanic membrane assessed on a semi-quantitative scale from 0 to 6. Other criteria, assessed on semi-quantitative scales, included relief of pain (0 or 1), rectal temperature (0 to 2), and overall evaluation by parents of the improvement of quality of life on three items: appetite (0 to 2), sleep (0 to 2) and playing activity (0 to 2). The results at D2 were as follows: there was no significant difference between treatment groups as to the main criterion, but only a trend for IBU and PARA to do better than PLA but not for IBU to do better than PARA. From these data there is no argument to emphasize the utility of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating the inflammatory signs of the tympanic membrane in otitis. There was a statistically significant difference between treatment groups at D2 for pain, IBU being superior to PLA (P < 0.01): 7%, 10% and 25% of the children were still suffering at D2 in the IBU, PARA and PLA treatment groups, respectively. The difference between PARA and PLA for pain was not statistically significant. There was no significant difference between treatment groups for the other criteria. All treatments were well and equally tolerated. Although no significant difference was found between the treatment groups on the aspect of the tympanic membrane, the efficacy of IBU was evidenced on the relief of pain, the symptom that most disturbs the child.     

外用非甾体类消炎药治疗骨关节炎疗效的Meta分析

目的评价外用非甾体类消炎药治疗骨关节炎的疗效.方法计算机检索MEDLINE,EMBASE,SCI,CINAHL, Cochrane图书馆和中国生物医学文献数据库等.手工检索已发表和未发表的所有外用非甾体类消炎药随机对照试验,对其逐个进行质量评价,并合并数据进行Meta分析.检索时间截至2005年3月30日.结果共纳入13 篇随机对照试验 ,包括1 983例患者,均为高质量研究.对治疗有效率的Meta分析结果显示,外用非甾体类消炎药治疗骨关节炎引起的疼痛仅在第1、2周疗效优于安慰剂,疼痛减轻的效应量分别是0.41[95%CI (0.16,0.660)]和0.40[95%CI(0.15,0.65)],而第3、4周疗效与安慰剂比较差异无统计学意义.结论现仅有短期(<4周)的随机对照试验评价外用非甾体类消炎药治疗骨关节炎的疗效.外用非甾体类消炎药用于治疗骨关节炎的疗效仅在第1、2周优于安慰剂,2周后其疗效与安慰剂的差异无统计学意义.目前还没有足够的临床试验证明,使用非甾体类消炎药治疗骨关节炎超过2周仍然有效.     

Impact of nurse prescribing: a qualitative study

AIM: This paper is a report of an investigation of the impact of prescribing on a group of recently qualified nurse prescribers in the United Kingdom. BACKGROUND: The creation of advanced nursing roles, and specific skills such as nurse prescribing, has resulted in nurses taking on roles that have traditionally been associated with doctors. The non-doctor prescribing initiative is continually developing and many nurses are now able to prescribe independently from almost the same range of medicines as doctors. Despite the advantages that appear to stem from nurses prescribing, some nurse researchers have been cautious about the impact that prescribing may have on the nursing profession. METHOD: Interviews were conducted during 2005 and 2006 with 45 nurse prescribers. All nurses had successfully qualified and registered as prescribers. Interviews were analysed thematically in line with the principles of grounded theory. FINDINGS: Prescribing allows nurses to overcome difficulties in the healthcare system that previously delayed patients' access to medicines. Prescribing is viewed as more than an 'add on' to current roles, it complements many aspects of nursing and integrates previously diffuse aspects of the nursing role. This enables nurses to adopt a more holistic approach to patient care and prescribing. Prescribing has the potential to increase job satisfaction and autonomous working, with the result that nurses are more likely to involve patients in decision-making about their care. CONCLUSIONS: Prescribing enhances nurses' knowledge about medication and increases their confidence to engage in prescribing decisions across the healthcare team. Nurse prescribing has the potential to improve service-user care, enhance collaboration and widen discussions about medicines. However, team members need to be prepared for the impact nurse prescribing could have on the dynamics of the multidisciplinary team. Preparatory information about nurse prescribing should be provided to all team members by trainee nurse prescribers. Information could include details about the proposed scope of future prescribing roles, allowing team members to consider how their roles could develop.     

Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused placenta

Summary— Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as a racemic (rac) mixture of S -(+)- and R -(-)-isomers. Its inhibitory effect on prostaglandin biosynthesis resides virtually in the S -form. Interestingly, R -ketoprofen does not undergo substantial metabolic inversion in humans. Though contraindicated during the last trimester of pregnancy, NSAIDs, including ketoprofen, are used as tocolytic agents in some cases. The S/R plasma concentration ratio was reported to average 2.3 in premature neonates whose mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma. Thus, we investigated the placental transfer of rac-ketoprofen in vitro using Schneider's perfused human cotyledon model. Glucosed Earle solutions with and without human serum albumin (HSA) were used. Several maternal perfusates were tested with different rac-ketoprofen concentrations together with 20 mg L⁻¹ of antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a specific HPLC method with derivatization procedure. HSA concentrations in maternal perfusate influenced the placental transfer of ketoprofen enantiomers. In the absence of HSA in the maternal perfusate, the S -(+)/ R -(-) concentration ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged 1.44 after addition of HSA 10 g L⁻¹ on the maternal side. Similar results were found for dialysis experiments using an inert Spectrapor 2 membrane suggesting that the S -(+)-free concentration is superior to the R -(-)-free concentration in the presence of HSA. Direct measurements of the free concentrations by centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data observed in vivo may result, at least in part, from the stereoselective protein binding of ketoprofen.     

Socio-demographic differences in adherence to evidence-based drug therapy after hospital discharge from acute myocardial infarction: a population-based cohort study in Rome, Italy

What is known and Objective: Adherence to evidence‐based drug therapy after acute myocardial infarction has increased over the last decades, but is still unsatisfactory. Our objectives are to set out to analyse patterns of evidence‐based drug therapy after acute myocardial infarction (AMI), and evaluating socio‐demographic differences. Methods: A cohort of 3920 AMI patients discharged from hospital in Rome (2006–2007) was selected. Drugs claimed during the 12 months after discharge were retrieved. Drug utilization was defined as density of use (boxes claimed/individual follow‐up; chronic use = 6+ boxes/365 days) and therapeutic coverage, calculated through Defined Daily Doses (chronic use: ≥80% of individual follow‐up). Patterns of use of single drugs and their combination were described. The association between poly‐therapy and gender, age and socio‐economic position (small‐area composite index based on census data) was analysed through logistic regression, accounting for potential confounders. Results and Discussion: Most patients used single drugs: 90·5% platelet aggregation inhibitors (antiplatelets), 60·0%β‐blockers, 78·1% agents acting on the renin–angiotensin system (ACEIs/ARBs), 77·8% HMG CoA reductase inhibitors (statins). Percentages of patients with ≥80% of therapeutic coverage were 81·9% for antiplatelets, 17·8% for β‐blockers, 64·4% for ACEIs/ARBs and 76·1% for statins. The multivariate analysis showed gender and age differences in adherence to poly‐therapy (females: OR = 0·84; 95% CI 0·72–0·99; 71–80 years age‐group: OR = 0·82; 95% CI 0·68–0·99). No differences were observed with respect to socio‐economic position. What is new and Conclusion:  The availability of information systems offers the opportunity to monitor the quality of care and identify weaknesses in public health‐care systems. Our results identify specific factors contributing to non‐adherence and hence define areas for more targeted health‐care interventions. Our results suggest that efforts to improve adherence should focus on women and older patients.     

A Randomized, Double-Blind, Placebo-Controlled Study of Preemptively Administered Intravenous Parecoxib: Effect on Anxiety Levels and Procedural Pain During Epidural Catheter Placement for Surgical Operations or for Chronic Pain Therapy

Background: The effect of parecoxib, when used perioperatively or during interventional techniques, is well demonstrated in the literature. Little is known about its effects on anxiety levels before the analgesic technique application. The aim of this prospective, randomized, double‐blind, placebo‐controlled, clinical study is to investigate whether parecoxib, preemptively administrated, has an effect on anxiety levels reported prior to an epidural puncture, and if it influences the reported pain of the interventional technique itself. Material and Methods: The study protocol involved 110 patients, scheduled for epidural catheter placement for chronic pain therapy—Group I, as well as 112 patients scheduled for orthopedic operations under epidural anesthesia—Group II. Patients in each group were randomly allocated into two subgroups in relation to parecoxib/placebo administration before epidural catheter placement: Group Ia, parecoxib 40 mg i.v. (n = 54), Group Ib, placebo (n = 56), Group IIa, parecoxib 40 mg i.v. (n = 57), Group IIb, placebo (n = 55). Patients were given a self‐administered inventory to measure the anxiety level of the presurgical/preprocedural state (State‐Trait Spielberger Anxiety Inventory) and anxiety levels were recorded 1 hour before epidural puncture, 20 minutes postdosing, and 1 hour after epidural catheter placement. Anxiety levels were also measured and recorded using visual analog scale (VAS). One hour after epidural puncture, reported procedural pain was recorded (VAS). One hour and 6 hours postepidural, patients' satisfaction was also recorded, on a 4‐point scale. Results: All four subgroups were similar regarding demographic, operative/procedural data, and coexisting diseases. Preprocedural anxiety levels were significantly decreased with parecoxib administration in comparison with placebo in both groups (P < 0.05). Reported VAS regarding pain from epidural puncture was lower in Groups IA and Ib. Patients' satisfaction was greater with parecoxib in comparison with placebo. Conclusion: The levels of anxiety have been investigated in several medical procedures and early, in the study of pain. The higher the expectation of pain and the anxiety are, the higher the intensity of the pain. Parecoxib seems to exert positive influence on pain and anxiety levels of interventional procedure. Further studies are needed to elucidate the actual mechanisms that are involved.     

Balancing trust and power: a qualitative study of GPs perceptions and strategies for retaining patients in preventive health checks

Objective: Little is known about how strategies of retaining patients are acted out by general practitioners (GPs) in the clinical encounter. With this study, we apply Grimens’ (2009) analytical connection between trust and power to explore how trust and power appear in preventive health checks from the GPs’ perspectives, and in what way trust and power affect and/or challenge strategies towards retaining patients without formal education.

Design: Data in this study were obtained through semi-structured interviews with GPs participating in an intervention project, as well as observations of clinical encounters.

Results: From the empirical data, we identified three dimensions of respect: respect for the patient’s autonomy, respect for professional authority and respect as a mutual exchange. A balance of respect influenced trust in the relationship between GP and patients and the transfer of power in the encounter. The GPs articulated that a balance was needed in preventive health checks in order to establish trust and thus retain the patient in the clinic. One way this balance of respect was carried out was with the use of humour.

Conclusions: To retain patients without formal education in the clinical encounter, the GPs balanced trust and power executed through three dimensions of respect. In this study, retaining patients was equivalent to maintaining a trusting relationship. A strategic use of the three dimensions of respect was applied to balance trust and power and thus build or maintain a trusting relationship with patients.

• KEY POINTS

• Little is known about how strategies for retaining patients are acted out by GPs in preventive health checks.

• ?? Retaining patients requires a balance of trust and power, which is executed through three dimensions of respect by the GPs.

• ?? Challenges of recruiting and retaining patients in public health initiatives might be associated with the balance of respect.