Summary
What is known and objective
Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between ...general practitioners (GPs), pharmacists and patients) on medication‐related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes.
Methods
An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication‐related hospitalizations based on old age, use of five or more medicines, non‐adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow‐up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP. The primary outcome of the study was the frequency of hospital admissions related to medication within the study period of 12 months for each patient. Secondary outcomes were survival, quality of life and ADEs.
Results and discussion
364 intervention and 310 control patients were included. Less medication‐related hospital admissions were found in the intervention group (n = 6; 1·6%) than in the control group (n = 10; 3·2%) but the overall effect was not statistically significant (hazard ratio (HR) 0·50, 95% confidence interval (CI) 0·12–1·59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis showed that the effect of the intervention was statistically significant for patients with five diseases or more: five diseases, HR 0·28 (95% bootstrap CI: 0·056–0·73) and eight diseases, HR 0·11 (95% CI: 0·013–0·34).
What is new and conclusion
A multicomponent pharmaceutical care intervention does not prevent medication‐related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication‐related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials.
Impaired placental development is a major cause of fetal growth restriction (FGR) and early detection will therefore improve antenatal care and birth outcomes. Here we aim to investigate serial ...first-trimester ultrasound markers of utero-placental (vascular) development in association with embryonic and fetal growth.
In a prospective cohort, we periconceptionally included 214 pregnant women. Three-dimensional power Doppler ultrasonography at 7, 9 and 11 weeks gestational age (GA) was used to measure placental volumes (PV) and basal plate surface area by Virtual Organ Computer-aided AnaLysis™, and utero-placental vascular volume (uPVV), crown-rump length (CRL) and embryonic volume (EV) by a V-scope volume rendering application. Estimated fetal weight (EFW) was measured by ultrasound at 22 and 32 weeks GA and birth weight percentile (BW) was recorded. Linear mixed models and regression analyses were applied and appropriately adjusted. All analyses were stratified for fetal sex.
PV trajectories were positively associated with CRL (βadj = 0.416, 95%CI:0.255; 0.576, p < 0.001), EV (βadj = 0.220, 95%CI:0.058; 0.381, p = 0.008) and EFW (βadj = 0.182, 95%CI:0.012; 0.352, p = 0.037). uPVV trajectories were positively associated with CRL (βadj = 0.203, 95%CI 0.021; 0.384, p = 0.029). In girls, PV trajectories were positively associated with CRL (p < 0.001), EV (p = 0.018), EFW (p = 0.026), and uPVV trajectories were positively associated with BW (p = 0.040). In boys, positive associations were shown between PV trajectories and CRL (p = 0.002), and between uPVV trajectories and CRL (p = 0.046).
First-trimester utero-placental (vascular) development is associated with embryonic and fetal growth, with fetal sex specific modifications. This underlines the opportunity to monitor first-trimester placental development and supports the associations with embryonic and fetal growth.
•First-trimester PV1 and uPVV2 trajectories estimate utero-placental development.•PV and uPVV trajectories are positively associated with embryonic and fetal growth.•Fetal sex modifies associations between placental development and antenatal growth.•First-trimester PV and uPVV more closely reflect early than late fetal growth.
Objectives
Depression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and ...hypoglycaemia.
Methods
Based on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI).
Results
Overall, the use of antidepressants was associated with hyperglycaemia ROR 1.52 (95% CI: 1.20–1.93) and of hypoglycaemia ROR 1.84 (95% CI: 1.40–2.42). The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT
2c
receptor, histamine-
1
receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter.
Conclusion
The results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.
Summary
What is known and objective
It is often necessary to adjust drug therapy if renal function is impaired in elderly patients taking drugs for diabetes and/or cardiovascular disease that are ...cleared by the kidneys. Although clinical guidelines recommend regular monitoring of renal function in these patients, in practice adherence to these recommendations varies from 28% to 75%. To determine whether drug dosing is appropriate, pharmacists need have up‐to‐date information about patients' renal function. In this study, the feasibility of point‐of‐care creatinine testing (POCCT) in a community pharmacy was evaluated as part of monitoring the drug therapy of ambulatory elderly patients.
Methods
Elderly patients on maintenance therapy with renally excreted drugs for diabetes or cardiovascular disease were eligible for POCCT. After informed consent was obtained, POCCT was performed by trained personnel. A pharmacist assessed the clinical relevance of electronically generated drug alerts based on the patient's calculated renal function and the Dutch guidelines for adjusting drug dosage in patients with chronic kidney disease. If appropriate, the patient's general practitioner (GP) was consulted and adjustments to treatment were communicated to the patient. The feasibility of POCCT was evaluated by means of questionnaires completed by patients and healthcare professionals (GPs and pharmacists).
Results
Of 338 potentially eligible patients, 149 (44%) whose renal function was not known were asked, by letter, to participate in the study. Of these individuals, 46 (31%) gave their informed consent and underwent POCCT. Response rates for completing the patient and professional questionnaires were 87% and 100%, respectively. More than half of the patients who underwent POCCT had mild‐to‐moderate renal impairment. On the basis of information provided by patients and healthcare professionals, POCCT would appear to be feasible in community pharmacies.
What is new and conclusion
POCCT improves the management of drug therapy by community pharmacists and is feasible in daily practice.
The high prevalence of drug-related problems (DRPs) in the elderly, occurring as a result of multiple drug use combined with age-related changes in pharmacokinetics and pharmacodynamics, is a well ...known phenomenon. However, effective intervention strategies are uncommon.
A pharmacy-based controlled trial (SMOG Screening Medicatie Oudere Geneesmiddelgebruiker; Screening Medications in the Older Drug User) was performed to investigate whether a community pharmacist-led intervention reduces the number of potential DRPs in patients aged > or = 65 years using six or more drugs concomitantly.
This intervention study was conducted from June 2002 until June 2003 in 16 community pharmacies in the Netherlands. Medication assessment was undertaken in elderly patients aged > or = 65 years using six or more drugs concomitantly on the date of inclusion. Ten types of potential DRPs were determined and grouped into the following three categories: (i) patient-related potential DRPs: non-compliance; (ii) prescriber-related potential DRPs: expired indication, therapeutic duplication, inappropriate dosage (over- and under-dosage), off-label use, undertreatment, inconvenience of use; and (iii) drug-related potential DRPs: contraindications, drug-drug interactions, drug treatment of adverse drug reactions. A list of recommended changes in medication was compiled by the pharmacist for the patients in the intervention group. Recommendations for medication change were discussed with the general practitioner (GP). Four months after the date of inclusion, the medications of each patient were again reviewed and screened for potential DRPs. The primary outcome corresponded to the change in the number of potential DRPs; the secondary outcome was related to the change in number of used medications between the intervention group and the control group at baseline and 4 months later.
A total of 174 patients were analysed: 87 patients in the intervention arm and 87 patients in the usual care arm. After a 4-month period, we observed a significant reduction in the mean number of DRPs per patient (mean difference -16.3%; 95% CI -24.3, -8.3). The mean number of drugs per patient was not significantly reduced (mean difference -4.7%; 95% CI -9.6, 0.2).
This study showed a positive influence of the community pharmacist in reducing potential DRPs in the elderly. Future interventions should also focus on actual outcomes, including quality of life, morbidity and mortality.
Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the ...complexity of the genotype–phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases.
•This algorithm will guide the clinician through the diagnostic process of EOA.•We provide clear phenotypic descriptions to target genetic investigations.•The reader will obtain an overview of known genetic causes.
Abstract Purpose To study incidence of local recurrences, postoperative complications and survival, in patients with rectal carcinoma aged 75 years and older, treated with either surgery and ...pre-operative 5 × 5 Gy radiotherapy or surgery alone. Patients and methods A random sample of patients aged over 75 years with pT2-T3, N0-2, M0 rectal carcinoma diagnosed between 2002 and 2004 in the Netherlands was included, treated with surgery alone ( N = 296) or surgery in combination with pre-operative radiotherapy ( N = 346). Information on local recurrent disease, postoperative complications, ECOG-performance score and comorbidity was gathered from the medical files. Results Local recurrences developed less frequently in patients treated with pre-operative radiotherapy compared to surgery alone (2% vs 6%, p = 0.002). Postoperative complications developed more frequently in irradiated patients (58% vs 42%, p < 0.0001). Especially deep infections (anastomotic leakage, pelvic abscess) were significantly increased in this group (16% vs 10%, p = 0.02). 30-day mortality was equal in both groups (8%). A significant increase in postoperative complication rate and 30-day mortality was only seen in those with “severe comorbidity” compared to patients without comorbidity (respectively 58% and 10% vs 43% and 3%), COPD (59% and 12%), diabetes (60% and 11%) and cerebrovascular disease (62% and 14%). In multivariable analysis, postoperative complications predicted 5-year survival. Conclusion Elderly patients receiving pre-operative radiotherapy show a lower local recurrence rate. However, as incidence rates of local recurrent disease are low and incidence of postoperative complications is increased in irradiated patients, omitting preoperative RT may be suitable in elderly patients with additional risks for complications or early death.
Background and aim: Isolated polycystic liver disease (PCLD) is characterized by the presence of multiple cysts in the liver in the absence of polycystic kidneys. The clinical profile of PCLD is ...poorly defined and we set up a study for the clinical characteristics of PCLD.
Methods: We collected clinical data on 188 PCLD patients (defined as >10 liver cysts) from five tertiary referral centres, and 137 patients were selected for the purpose of this study. We performed molecular analysis of the PCLD associated genes PRKCSH and SEC63 in 91 patients.
Results: A total of 118 (86%) patients were female. The majority of patients (88%) had >20 cysts. The median age at diagnosis was 47 years (range 23–84). 37 (41%) patients carried a mutation. Clinical symptoms at presentation were present in 111 (84%) patients. γ‐glutamyl transferase was elevated to 1.4 times upper limit of normal (interquartile range 1.0–2.7). The presence of a mutation and female gender predicted a more severe course: female patients were 9 years younger at the time of diagnosis (47 years; range 23–84) and 91% had symptoms (P<0.01); likewise, mutation carriers were younger at presentation (39 years; range 35–48) and 95% of this cohort had symptoms (P<0.01). During follow‐up median 8.2 years (range 0–35), 10% of untreated and 51% of treated patients developed complications. Mortality in this cohort was 8%, but only 2% died of PCLD‐related causes. 58% of patients were treated a median of 2 years (range 0–25) after diagnosis.
Conclusion: Symptomatic PCLD patients are mainly females. Females and mutation carriers were younger at diagnosis and had a more severe course of disease.
Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.
In this multicenter retrospective cohort ...study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 6958-77years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.
In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio OR4.68, 95%confidence interval 4.02-5.45, OR0.680.59-0.79, respectively;both p< 0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.650.55-0.75, DM OR1.471.26-1.72, CKD OR1.611.32-1.97, COPD OR1.301.07-1.59). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.
Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.
CAPACITY-COVID ( NCT04325412 ).
Medication can be effective but can also be harmful and even cause hospital admissions. Medication review or pharmacotherapy review has often been proposed as a solution to prevent these admissions ...and to improve the effectiveness and safety of pharmacotherapy. However, most published randomised controlled trials on pharmacotherapy reviews showed no or little effect on morbidity and mortality. Therefore we designed the PHARM (Preventing Hospital Admissions by Reviewing Medication)-study with the objective to study the effect of the total pharmaceutical care process on medication related hospital admissions and on adverse drug events, survival and quality of life.
The PHARM-study is designed as a cluster randomised, controlled, multi-centre study in an integrated primary care setting. Patients with a high risk of a medication related hospital admission are included in the study with randomisation at GP (general practitioner) level. We aim to include 14200 patients, 7100 in each arm, from at least 142 pharmacy practices.The intervention consists of a patient-centred, structured, pharmaceutical care process. This process consists of several steps, is continuous and occurs over multiple encounters of patients and clinicians. The steps of this pharmaceutical care process are a pharmaceutical anamnesis, a review of the patient's pharmacotherapy, the formulation and execution of a pharmaceutical care plan combined with the monitoring and follow up evaluation of the care plan and pharmacotherapy. The patient's own pharmacist and GP carry out the intervention. The control group receives usual care.The primary outcome of the study is the frequency of hospital admissions related to medication within the study period of 12 months of each patient. The secondary outcomes are survival, quality of life, adverse drug events and severe adverse drug events. The outcomes will be analysed by using mixed-effects Cox models.
The PHARM-study is one of the largest controlled trials to study the effectiveness of the total pharmaceutical care process. The study should therefore provide evidence as to whether such a pharmaceutical care process should be implemented in the primary care setting.
NTR 2647.
PDF
