Confidence and accuracy in identification of adverse drug reactions reported by outpatients

Background Patient reporting of adverse drug reactions (ADRs) could supplement the existing reporting system and contribute to early detection of ADRs. The confidence in ADR identification and their attribution of ADRs were limited to outpatients. Objective To determine the type and frequency of ADRs reported by outpatients, to evaluate confidence and accuracy in ADR identification as well as contributing factors. Setting University hospital in northeastern Thailand Method Cross-sectional study using questionnaires distributed to 500 outpatients who claimed to have experienced an ADR. Confidence in identifying ADRs was measured by visual analogue score (VAS), while accuracy of reported ADRs was determined using Naranjo algorithm and WHO criteria. Main outcome measure Number and type of ADRs, confidence rating and accuracy category. Results In total, 390 outpatients completed the questionnaire (response rate?=?78.0%). Rash (19.0%), nausea/vomiting (7.4%), and dizziness (5.8%) were the top three reported ADRs. Sixty-one percent of respondents rated their level of confidence in identifying ADRs as high (VAS 9.2?±?0.95), which was associated with having underlying diseases (OR 1.93), low number of reported symptoms (OR 0.38) and severe ADRs (OR 1.33). Causality assessment was classified as true ADRs in 90.0% and 88.9% of cases, using Naranjo algorithm and WHO criteria, respectively. Respondents with low number of reported symptoms (OR 0.27) and high level of confidence had greater accuracy in ADR identification (OR 1.11). Conclusion The outpatients reported a high proportion of potential ADRs with high confidence and accuracy. Patient reporting of ADRs has potential to support the pharmacovigilance system.     

Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance

Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥?18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient’s adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.     

Antihypertensive-related adverse drug reactions among older hospitalized adults

Background Antihypertensive medications are commonly used for a wide range of indications, yet it is unknown to what extent older adults are at risk of adverse drug reactions (ADRs) associated with their antihypertensive medication use. Objective The aim of this study was to determine the prevalence and characteristics of antihypertensive-related ADRs on hospital admission. Setting Metropolitan teaching hospital in Sydney, Australia. Method A retrospective cross-sectional audit of 503 older patients (≥ 65 years) admitted to hospital was conducted. Potential ADRS were identified from the medical record. Two independent clinical pharmacists reviewed each potential ADR using validated tools for causality, severity, preventability and contribution to hospitalization. Characteristics associated with an increased ADR risk among antihypertensive users were identified via logistic regression. Main outcome measure Antihypertensive related ADRs. Results Antihypertensives were used on admission by 68% of the cohort and the prevalence of ‘definite/probable’ antihypertensive-related ADRs among antihypertensive users was 16.4%. Antihypertensive medications were associated with a threefold ADR risk (OR = 3.09, 95% CI 1.85–5.16). Angiotensin II Receptor Blockers (ARB), impaired renal function, recent medication changes and previous history of allergy or ADR were all associated with an increased risk of experiencing an ADR. Conclusions ADRS associated with antihypertensive medicines were relatively common among older adults admitted to hospital. Increased awareness of those older persons who are most at risk of experiencing an antihypertensive-related ADR in the clinical setting may lead to early detection and minimization of ADR associated harms.     

Effects of e-mails containing ADR information and a current case report on ADR reporting rate and quality of reports

Background

Spontaneous reporting of adverse drug reactions (ADRs) is one approach to increasing our knowledge on the risks of drugs in clinical practice. Under-reporting is a shortcoming of this system.

Objectives

To evaluate if repeated e-mails with attachments on ADR information can affect (1) the reporting of ADRs and (2) the quality of the ADR reports.

Methods

All 117 heads of primary health care units in the region of Västra Götaland in Sweden were randomly allocated (1:1) to an intervention group or a control group. The intervention consisted of e-mails with attachments sent out to each of the 117 heads in January, May and September 2007. These e-mails included (1) the heading “Every ADR report is important”, (2) a current case report of an ADR and (3) instructions on how to report. The number of reports from each primary health care unit run by the same head was registered, as was the quality of the report. The quality was defined as high if the ADR was (1) serious, (2) unexpected or (3) related to the use of new drugs and not labeled as common in the summary of product characteristics. All other reports were regarded as low-quality reports.

Results

The total number of reports increased from 89 in 2006 to 111 in 2007 (P?=?0.037). No difference in the number of reports between intervention (n?=?56) and control (n?=?55) units could be detected. The proportion of high-quality reports before and after the intervention was 36 and 48%, respectively (intervention, P?=?0.11) and 40 and 36%, respectively (control, P?=?0.55).

Conclusions

No apparent effect of repeated ADR e-mails on the reporting of ADRs could be detected, although an increase in the reporting rate in general was noted.

     

Factors associated with adverse drug reactions in older inpatients in teaching hospital

Background Adverse drug reactions (ADRs) occur frequently during hospital stays and are an important public health problem, particularly in the care of the older. Objectives This study aimed to determine the prevalence of ADRs among older inpatients and the factors associated with their occurrence. Setting Brazilian teaching hospital. Methods This was a cross-sectional study with older inpatients in the internal medicine ward of a teaching hospital. The dependent variable was the occurrence of an ADR during hospitalization. The independent variables were gender, age, length of hospitalization, number of health problems, medications, and potentially inappropriate medications for the older. Logistic regression was performed to analyze the association between an ADR and the independent variables. Main outcome measure Factors associated with ADR in older inpatients. Results Among the 237 inpatients investigated, 50 (21.1%) developed at least one ADR. The total number of ADRs observed was 62 and the most frequent were acute kidney injury, hypotension, and cutaneous adverse reactions A multivariate analysis demonstrated a positive and independent association between the occurrence of an ADR and the presence of heart failure [odds ratio (OR) 2.4; 95% confidence interval (CI) 1.2–4.6], and with hospitalization time exceeding 12 days (OR 2.3; 95% CI 1.2–4.4). Conclusions The study showed a high prevalence of ADRs among the older and a positive association with hospitalization time and heart failure. Understanding the factors associated with the occurrence of ADRs among older inpatients provides elements for improving the safety of care and optimization of pharmacotherapy.     

Underreporting in pharmacovigilance: an intervention for Italian GPs (Emilia–Romagna region)

Purpose

Underreporting is a major limitation of spontaneous reporting systems for suspected adverse drug reactions (ADRs). Several interventions to increase the ADR reporting rate have been proposed, but their efficacy remains poorly investigated.

Methods

This was a questionnaire study aimed at assessing the knowledge, attitudes, and behavior of general practitioners (GPs) regarding ADR reporting and at evaluating whether a monthly e-mail-based newsletter on drug safety could affect the rate and the quality of the ADR reports submitted by these GPs. Three local health authorities (LHAs) of the Emilia–Romagna region were chosen on the basis of their ADR reporting rate during the period preceding the study: Rimini (high), Ferrara (average), and Piacenza (low reporting rate). All GPs (n?=?737) associated with these three LHAs were recruited. The pooled number of ADR reports sent by GPs in the remaining seven LHAs of the region was used as controls. The study covered a period of 3 years and was divided into: (1) identification of the reasons leading to underreporting through a questionnaire (Phase I); (2) the intervention, i.e., sending a newsletter for a 10-month period (Phase II); (3) evaluation of the intervention outcomes during the 10 months following the period in which the newsletter had been received (Phase III).

Results

Among GPs involved, 22.8 % returned the questionnaire. Over 94 % of the respondents considered the spontaneous reporting of suspected ADRs to be part of their professional obligations, but only 6.5 % had submitted at least one report in the previous 6 months. Following the completion of Phase II, the overall number of reports coming from the LHAs subjected to the intervention rose by 49.2 % compared to 2009, while the number of reports coming from the control LHAs increased by 8.8 %. Rimini and Piacenza showed a 200 % increase in the number of ADR reports submitted by GPs, while the number of ADR reported submitted by the control group decreased by 25.5 %. In 2011, the number of overall ADRs reports from the LHAs subjected to the intervention decreased by 6.8 %; this decrease reached 50.0 % of the GPs. Control HLAs showed an overall decline of 4.3 %, while the total number of ADRs from GPs increased by 63.3 %. Ferrara was excluded from the analysis due to confounding factors.

Conclusions

The periodic e-mail update on the safety of drugs represents an effective and inexpensive way to raise the awareness of GPs on the importance of spontaneous ADR reporting. Since the outcome of the intervention seemed to disappear after the intervention was stopped, there appears to be a need to adopt a policy of regular updates and educational strategies for health professionals.     

Pharmacovigilance in China: development and challenges

Background Rational drug use and drug safety are becoming increasingly important concerns in China with the increasing public access to drugs and the health-care system, and this has led to the development of pharmacovigilance in China. Aim of the review To provide a brief introduction about pharmacovigilance in China in terms of system development, utilization and challenges. Method Relevant studies on pharmacovigilance related to the study aim was undertaken through literature search to synthesize the extracted data. Results The creation and evolvement of China’s pharmacovigilance system spans across 30 years since 1989. The system consists of four progressing administrative layers: county, municipal, provincial and national levels. China has passed over 20 laws and regulations related to pharmacovigilance covering the processes of drug development, manufacture, distribution and use with the aim to guard drug safety. An online spontaneous self-reporting Adverse Drug Reaction (ADR) Monitoring System was established in 2003. ADRs are mainly reported by medical institutions, pharmaceutical manufacturers, and drug distributors. Currently there is no mandatory ADR reporting requirement for pharmaceutical manufacturers, and a proposed regulation under public comment will likely change this. China has started to build active pharmacovigilance surveillance programs in addition to the passive ADR reporting system. The China Food and Drug Administration has established the intensive Safety Monitoring Program and the National Adverse Drug Reaction Monitoring Sentinel Alliance Program based on electronic health records to further the efforts of ADR reporting, monitoring and analysis. Conclusion The practice of ADR monitoring and pharmacovigilance in China have made great progress. More efforts are needed both in system building, and creation of laws and regulations to strengthen the safe use of medicines.     

Factors that affect adverse drug reaction reporting among hospital pharmacists in Western China

Background Hospital pharmacists can make a considerable contribution to the spontaneous reporting system of adverse drug reactions. The factors that influence adverse drug reaction reporting among hospital pharmacists remain largely unknown in China. Objective This study aims to identify factors that affect hospital pharmacist-led adverse drug reaction reporting in Xi’an, and to obtain suggestions from pharmacists about how to improve the current adverse drug reaction reporting system. Setting Hospital settings throughout Xi’an, a region of Western China. Method A matched case–control study was conducted on a population of 2,814 hospital pharmacists in Xi’an during 2011. Cases included all pharmacists who had reported at least one adverse drug reaction between 2008 and 2010 and agreed to participate in the study (186/204; 91.2 %); controls (n = 372) were pharmacists who had not reported any adverse drug reaction during the same period. A self-administered questionnaire was distributed to the participants. Logistic regression was performed to evaluate the association between indicator variables and the outcome of having reported at least one adverse drug reaction. Main outcome measure Pharmacists’ knowledge, attitude and practice towards adverse drug reaction reporting and factors affecting reporting. Results Higher professional title (adjusted OR 1.44; 95 % CI 1.07–1.94; p = 0.018), having received training about adverse drug reaction reporting (1.64; 1.04–2.57; p = 0.032), better knowledge about reporting (1.53; 1.12–2.08; p = 0.007), “lack of access to adverse drug reaction reporting form” (0.29; 0.12–0.72; p = 0.008) was independently associated with adverse drug reaction reporting. Clinical pharmacists were more likely to report an adverse drug reaction than dispensary pharmacists (1/adjusted OR 5.26; p < 0.001), pharmacy administrators (5.00; p = 0.003), and other technicians (5.56; p = 0.001). Conclusions Higher professional title, having received training, mastering knowledge about reporting, and being a clinical pharmacist were positive predictors of pharmacist-led adverse drug reaction reporting. Lack of access to reporting forms was a negative predictor. Continuous training and establishing incentive mechanisms are needed to promote adverse drug reaction reporting among hospital pharmacists.     

Evaluation of adverse drug reactions in medical intensive care units

Purpose

Patterns of adverse drug reactions (ADRs) in the medical intensive care unit (MICU) were analysed, and signals for detecting ADRs were developed from the analysis.

Method

A retrospective study was conducted in MICU wards at a tertiary care teaching hospital in Seoul, Korea. The areas included one general MICU and one cancer centre MICU. Two pharmacists evaluated ADRs in terms of length of stay, causality, severity, preventability, types, related organs, and incidence. Differences in ADR perception rates between physicians and pharmacists were also evaluated. ADR cases detected through the evaluation were reviewed to develop specific alerting signals for ICU ADRs.

Results

The study group included 346 patients admitted to the ICU over 4 months. The overall incidence of ADRs was 32%. ICU length of stay is closely related to ADRs (p?=?0.014). Most ADR cases were mild, temporary, and harmful to the patient. Twenty percent of ADRs were preventable, and 74% were type A. Of the ADRs, 70% were noted by physicians; 80% required intervention. The most commonly implicated drug was amphotericin B, and the clinical presentation was a haematologic reaction. Data on the time required for pharmacists to identify ADRs indicated that they were not slower than physicians. Six signals for early detection of the ADRs were developed.

Conclusions

The overall ADR incidence in the MICU was about one-third, and the length of stay of the ADR group was longer than that of those without this experience. Automated signal generation was developed. It seemed to be a valuable tool for faster and more efficient patient management, and possibly prevention of ADRs. A future study should scientifically evaluate the clinical relevance of this tool.     

Exploring the impact of feedback on prescribing error rates: a pilot study

Background Prescribing errors are prevalent in hospital settings with feedback identified as one potential error reduction strategy. Hospital pharmacists work alongside prescribers at ward level and are credible facilitators of prescribing error feedback. A formalised programme of pharmacist-led prescribing error feedback was designed and implemented Objective To determine the impact of the feedback intervention on prescribing error rates. Method Prospective prescribing audits were undertaken at baseline for control (n = 11) and intervention group (n = 10) prescribers. The intervention group received pharmacist-led, individualised constructive feedback on their prescribing, whilst the control group continued with existing practice. Prescribing was re-audited following 3-months of the intervention. Data were analysed using chi-squared and independent t-tests. Results Error frequency (123/641 intervention and 121/649 control) was comparable between groups at baseline (p = 0.819) with significant differences (90/1677 intervention and 236/984 control) post intervention (p = <0.005). Prescribing error rates were lower in the intervention group (mean change of ?11.5%) and higher in the control group (mean change of +5.9%) following the intervention, with a mean significant difference of 17.4% (SD 4.7, 95% CI, ?27.3 to ?7.6), t = ?3.694, p < 0.05, between groups. Conclusion Pharmacist-led prescribing error feedback positively influences prescribing. This intervention shows promise for wider application in hospital settings to optimise patient safety.     

Improvement of time in therapeutic range with warfarin by pharmaceutical intervention

Background Anticoagulation therapy with warfarin is highly effective for prevention and treatment of thromboembolic disorders. Nevertheless, its management is challenging especially in developing countries, where the medical access is difficult and patient education is poor. Objective To determine the effect of pharmaceutical intervention (PI) on the time in therapeutic range (TTR) of a group of anticoagulated patients from our referral center. Method A group of consecutive outpatients previously treated by usual medical care underwent PI. The intervention consisted in the identification and avoidance of food and drug interactions, the confection of medication schedule charts and education to patients regarding side effects and drug monitoring. Mean TTR before and after PI was compared through the Wilcoxon test for repeated measures. Regression analyses were performed to assess the relationship between a TTR level under 65% and potential explanatory variables. Results Mean TTR before PI was 37.4 ± 23.5% and after PI it raised to 67.0 ± 24.9%. Mean change in TTR was +29.5% (95% CI 14.5–44.6; p < 0.001). Before PI only 4 patients had TTR values above 65%, in contrast to 18 patients after PI. Conclusion Our findings support the efficacy of PI to improve TTR values in patients treated with warfarin.     

Preventive effect of pre-warming,hot compress,and pH adjustment in oxaliplatin-induced venous pain

Background Venous pain induced by peripheral intravenous administration of oxaliplatin remains clinically unresolved. Objective The aim of this study was to determine the efficacy of comprehensive intervention care for venous pain in colorectal cancer patients receiving oxaliplatin. Setting A Japanese tertiary hospital. Method We treated all outpatients after April 2012 with comprehensive intervention care including pre-warming of the oxaliplatin solution, use of a hot compress, and pH adjustment by combination with dexamethasone. We retrospectively reviewed the electronic medical records from colorectal cancer patients who had received oxaliplatin via a peripheral vein between December 2009 and June 2014. Main outcome measures The primary endpoint of this study was the incidence of venous pain at the administration site during oxaliplatin infusion, according to injection site reaction grade ≥ 2. Results We evaluated 271 treatment courses in 59 patients. Venous pain occurred in 42 courses (15.5%) among 26 patients. Multivariate logistic regression analysis revealed that female gender and body mass index ≥ 25 kg/m² were significantly associated with an increased risk of venous pain during all courses (adjusted odds ratio [OR]: 3.18, 95% confidence interval [CI] 1.35–7.92; P < 0.01; and adjusted OR: 3.37, 95% CI 1.26–9.40; P = 0.02, respectively), whereas comprehensive intervention care were significantly associated with reduced risk of venous pain during all courses (adjusted OR: 0.10, 95% CI 0.02–0.44; P < 0.01). Conclusion Comprehensive intervention care is a clinical treatment option for oxaliplatin-induced peripheral venous pain in patients with colorectal cancer, especially females with obesity.     

Health care professionals’ and students’ attitude toward collaboration between pharmacists and physicians in Croatia

Background As traditional roles of pharmacists and physicians seem nowadays insufficient to ensure patient safety and therapy effectiveness, interprofessional collaboration has been suggested to improve health outcomes. Objective To assess and compare the attitudes of physicians and pharmacists, as well as medical and pharmacy students in Croatia, toward interprofessional collaboration in primary health care. Methods The study included 513 pharmacists and physicians, and 365 students of pharmacy and medicine from Croatia. The validated questionnaire, Scale of Attitudes Toward Physician–Pharmacist Collaboration, was translated in Croatian and completed, anonymously and voluntarily, by all participants. Results Pharmacists showed a more positive attitude toward collaboration than physicians (53.8 ± 4.8 vs. 50.7 ± 5.0). Pharmacy students expressed the most positive attitude (56.2 ± 4.9), while medical students showed the remarkably lowest attitude toward collaboration (44.6 ± 6.2). Conclusion Pharmacists and physicians in Croatia expressed a relatively positive attitude toward their collaboration, comparable with their colleges in the USA. On the other hand, medical students expressed a 21 % less positive attitude than pharmacy students which could have an effect on interprofessional collaboration in the future when those students start working as health care professionals. Future studies, focusing on the promotion of this collaboration, on both under-graduated and post-graduated level, are warranted.     

RETRACTED ARTICLE: Evaluation of pharmaceutical care in a diabetes ward from China: a pre-and post-intervention study

Objective To describe the development and implementation of pharmaceutical care services in a diabetes ward, and to examine the effectiveness of pharmacist interventions. Setting Tongde hospital of Zhejiang province, a 1,200-bed South China teaching hospital, serving the local community. Method A single-center, 2-phase (pre-/post-intervention phase) designs was performed in the diabetes ward of a general hospital. Patients in post-intervention phase (October 2012 to December 2012) received pharmaceutical care from a clinical pharmacist, while patients in the pre-intervention phase (January 2012 to March 2012) received routine medical care. The pre- and post-intervention phases were then compared to evaluate the outcomes of pharmacist interventions. Main outcome measure type and number of interventions, and medication errors assessed at the baseline and at the end of pharmaceutical care were the main outcome measures. Results During the 3-month study period, the clinical pharmacist made 240 interventions for 473 admitted patients; of these, 207 (86.3 %) were accepted by physicians or nurses, and dosage adjustment [n = 83, (34.6 %)] was the type of intervention implemented most often. In the group that received the participation of pharmacists, medication errors per patient decreased from 1.68 to 0.46 (p < 0.001); medication errors, of incorrect dose or dosing interval, were markedly improved (decreased from 0.87 to 0.14; p < 0.001), the drug cost per patient day decreased from $347.15 to $309.74 (p = 0.095), and the length of diabetes ward stay did not change significantly (16.14 vs. 15.93 days; p = 0.15). Conclusion The presence of the pharmacist in the diabetes ward resulted in significant reduction in medication errors and had potential drug-cost-saving effects.     

Standardising analgesic administration for nurses: a prospective intervention study

Background Uncontrolled pain reduces quality of life, delays recovery from surgery and can potentially contribute to the development of chronic pain. Strategies to improve pain management are desirable in view of these detrimental outcomes, yet frequently they are predominately medically based despite nurses playing key roles in pain assessment and analgesic administration. Objective To develop an algorithm-based guidance addressing nurses’ pain assessment and analgesic administration and investigating its impact on quality of pain management. Setting Two orthopaedic units in a university hospital. Method An interdisciplinary expert panel consisting of physicians, nurses and clinical pharmacists developed an algorithm-based guidance in analgesic administration for nurses. The guidance was based on current guidelines addressing the appropriate use of analgesics. In a prospective intervention study, clinical pharmacists acted as independent monitors who assessed nurses’ pain assessment and analgesic administration before (control period: usual care without any further support) and after implementation of the algorithm-based guidance (intervention period). We evaluated patient-nurse contacts for guideline adherence. We predefined guideline adherence (main outcome) as fulfilling all three of the following criteria: (A) nurses’ pain intensity assessment, (B) their assessment of the patients’ need for analgesics, and (C) analgesic administration depending on patients’ individual pain intensity (including choice of prescribed analgesics). Main outcome measure Adherence to pain management guidelines. Results We analysed 706 patient-nurse contacts with 162 patients in the control and 748 contacts with 168 patients in the intervention period. Without support, guidelines were followed in 6 % of the patient contacts. We achieved an increase to 54 % (p < 0.001) after guidance implementation (main outcome). Guideline adherence decreased with rising pain intensity (slope coefficient ?0.763, p < 0.001). Conclusion Especially in patients suffering from severe pain, current guidelines were not strictly followed by nurses when administering analgesics. Guideline adherence improved eightfold by implementing an algorithm-based guidance.     

Paediatric adverse drug reactions reported to the Spanish Pharmacovigilance System from 2004 to 2009

Purpose

This study was conducted to evaluate relevant new information about ADRs reported in the Spanish paediatric population over a 6-year period.

Methods

Adverse drug reactions (ADRs) for individuals aged 0–17?years reported to the Spanish Pharmacovigilance System from 2004 to 2009 were analysed with respect to time, age and sex, category of ADR [System Organ Class (SOC)], seriousness, suspected medicines [level 2 of the Anatomical Therapeutic Chemical (ATC) Classification System] and type of reporter.

Results

In total, 4,279 ADR reports corresponding to 8,196 ADRs were analysed, approximately two ADRs per report. The rate of paediatric ADR reports in 2009 was 165 per million, of which nearly half (46?%) were for children (age group 2–11?years). Similar total numbers of ADRs were reported for boys and girls. The most frequent ADRs reported were from the following SOCs: general disorders and administration site conditions (34?%); skin and subcutaneous tissue disorders (15?%); nervous system disorders (14?%). Reports encompassed medicines from various ATC groups: vaccines and anti-infectives for systemic use (67?%); nervous system (9?%); respiratory system (9?%). On average, 37?% of ADRs were classified as serious. There were 33 fatal ADRs, and 35?% of the paediatric population associated with the ADR notifications required hospitalization or extended hospital stay.

Conclusions

In Spain, ADR reporting rate in the paediatric population has increased since 2004. The proportion of suspected ADR reports related to vaccines was predominant, which highlights the important role played by nurses. ADR notification of congenital malformations in newborn infants highlights the need for joint action between the Spanish System of Pharmacovigilance of Medicines for Human Use (SEFV-H) and paediatricians, obstetricians and gynaecologists. The publication of safety reports by regulatory agencies is determinant for the increased number of ADR notifications.     

Regulation of the Human Fc-Neonatal Receptor alpha-Chain Gene <Emphasis Type="BoldItalic">FCGRT</Emphasis> by MicroRNA-3181

Purpose

FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs (hsa-miR-3181 and hsa-miR-3136-3p) acting on FCGRT.

Methods

The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells.

Results

Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P <?0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P <?0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P <?0.001). The mature form of hsa-miR-3181 was detected in samples of human liver.

Conclusions

These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.

     

Pharmaceutical care of elderly patients with poorly controlled type 2 diabetes mellitus: a randomized controlled trial

Background Care of the elderly with diabetes is more complicated than that for other age groups. The elderly and/or those with multiple comorbidities are often excluded from randomized controlled trials of treatments for diabetes. The heterogeneity of health status of the elderly also increases the difficulty in diabetes care; therefore, diabetes care for the elderly should be individualized. Motivated patients educated about diabetes benefit the most from collaborating with a multidisciplinary patient-care team. A pharmacist is an important team member by serving as an educator, coach, healthcare manager, and pharmaceutical care provider. Objective To evaluate the effects of pharmaceutical care on glycemic control of ambulatory elderly patients with type 2 diabetes. Setting A 421-bed district hospital in Nantou City, Taiwan. Method We conducted a randomized controlled clinical trial involving 100 patients with type 2 diabetes with poor glycemic control (HbA1c levels of ≥9.0 %) aged ≥65 years over 6 months. Participants were randomly assigned to a standard-care (control, n = 50) or pharmaceutical-care (intervention, n = 50) group. Pharmaceutical care was provided by a certified diabetes-educator pharmacist who identified and resolved drug-related problems and established a procedure for consultations pertaining to medication. The Mann–Whitney test was used to evaluate nonparametric quantitative data. Statistical significance was defined as P < 0.05. Main outcome measure The change in the mean HbA1c level from the baseline to the next level within 6 months after recruiting. Results Nonparametric data (Mann–Whitney test) showed that the mean HbA1c level significantly decreased (0.83 %) after 6 months for the intervention group compared with an increase of 0.43 % for the control group (P ≤ 0.001). Medical expenses between groups did not significantly differ (?624.06 vs. ?418.7, P = 0.767). There was no significant difference in hospitalization rates between groups. Conclusion The pharmacist intervention program provided pharmaceutical services that improved long-term, safe control of blood sugar levels for ambulatory elderly patients with diabetes and did not increase medical expenses.     

Safety of an injection with a mixture of extracts from <Emphasis Type="Italic">Herba Artemisiae annuae</Emphasis>, <Emphasis Type="Italic">Fructus Gardeniae</Emphasis> and <Emphasis Type="Italic">Flos Lonicerae</Emphasis>

Objective This study aimed to evaluate the safety for an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae and to determine the risk factors that may affect its adverse drug reactions. Methods A drug-oriented prospective observational study was performed. Physicians filled in clinical observation forms with detailed information of the patients including general information, drug information, therapeutic effects and adverse drug events. The adverse drug reaction factors were analyzed by both mono-factor and multiple-factor logistic regression methods. Results From April to July 2007, we collected 12,427 observation forms from 46 hospitals in Jiangsu Province of China. Among the 11,707 observation forms we analyzed, 8,074 patients were children younger than 14 years old (69%). Among 51 reported adverse drug events, 45 cases were adverse drug reactions. The total adverse drug reaction incidence of the injection was 0.38%. While most adverse drug reactions were previously known (e.g., rash, pruritus, vomiting and diarrhea), we observed three new ADR symptoms: shiver, phlebitis and anhelation. All the adverse drug reactions were controlled very well through the follow-up therapy, and none of them was life threatening. The mono-factor analysis showed that adverse drug reactions of the injection were significantly correlated with total medication dose (P = 0.0049) and combination medication (P = 0.0143), especially with antimicrobial drugs (P = 0.0079) and macrolides (P = 0.0017). The multiple factor analysis confirmed these results: medication dosage and combination medication had a crucial impact on adverse drug reactions of the injection; the risk was increased by 24.8% (the estimated value of relative risk was 1.248, 95% confidence interval: 1.054–1.479) and 89% (1.890, 1.001–3.566), respectively. Conclusion The total adverse drug reaction incidence of the injection was 0.38% and lower than we expected. Moreover, we observed three new adverse drug reactions, none of which was severe.