The impact of pharmaceutical care interventions for medication underuse in older people: a systematic review and meta-analysis

Aims

The aim of the present study was to conduct a meta-analysis of controlled trials assessing the impact of pharmaceutical care interventions (e.g. medication reviews) on medication underuse in older patients (≥65 years).

Methods

The databases MEDLINE and EMBASE were searched for controlled studies, and data on interventions, patient characteristics and exposure, and outcome assessment were extracted. Risk of bias was assessed using the Cochrane Collaboration’s ‘risk of bias’ table. Results from reported outcomes were synthesized in multivariate random effects meta-analysis, subgroup meta-analysis and meta-regression.

Results

From 954 identified articles, nine controlled studies, mainly comprising a medication review, were included (2542 patients). These interventions were associated with significant reductions in the mean number of omitted drugs per patient (estimate from six studies with 1469 patients: – 0.44; 95% confidence interval –0.61, –0.26) and the proportion of patients with ≥1 omitted drugs (odds ratio from eight studies with 1833 patients: 0.29; 95% confidence interval 0.13, 0.63). The only significant influential factor for improving success was the utilization of explicit screening instruments when conducting a medication review (P = 0.033).

Conclusion

Pharmaceutical care interventions, including medication reviews, can significantly reduce medication underuse in older people. The use of explicit screening instruments alone or in combination with implicit reasoning is strongly recommendable for clinical practice.     

Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas

OBJECTIVE  The human pituitary gland is affected selectively by conditions associated with iron deposition, but the mechanisms for this are unknown. In this study we have determined whether the transferrin receptor, which mediates iron uptake by cells, could be detected immunocytochemically in human pituitary adenomas in vitro .
PATIENTS  Data were derived from 35 patients undergoing transsphenoidal surgery and included 13 with clinically non-functioning adenomas, 15 with acromegaly, 4 prolactinomas, 2 patients with Cushing's disease and one patient with Nelson's syndrome.
MEASUREMENTS  Transferrin receptor immunopositivity was determined for each adenoma in dispersed cell culture using a specific monoclonal antibody.
RESULTS  Eight of 13 clinically functionless adenomas showed immunopositive transferrin receptor expression, whilst adenomas from 15 patients with acromegaly, 4 prolactinomas, 2 Cushing's syndrome and one patient with Nelson's syndrome were negative. The eight transferrin receptor positive tumours were gonadotrophinomas and accounted for eight of the nine tumours which secreted and immunostained for FSH; all eight also secreted and immunostained for LH.
CONCLUSIONS  These findings may reflect a special requirement for iron by gonadotrophin secreting cells in comparison to other pituitary cell types and this could underlie the reasons why in the normal pituitary these cells are especially susceptible to malfunction in iron overload syndromes such as genetic haemochromatosis and β-thalassaemia.     

Haematological reconstitution following high dose and supralethal chemo-radiotherapy using stored, non-cryopreserved autologous bone marrow

S ummary . Eighteen patients with small cell carcinoma of the lung received high dose cyclophosphamide (180–200 mg/kg) intensification following five pulses of 'CHOP' chemotherapy (cyclophosphamide 750 mg/m² i.v., adriamycin 50 mg/m² i.v., vincristine 1·4 mg/m² i.v., prednisolone 40 mg orally for 5 d). They received infusions of autologous bone marrow which had been stored at 4°C for 34 h. Pancytopenia was predictable in onset and its duration acceptable. Recovery of neutrophils to greater than 1·0 × 10⁹/l was achieved in 17·5 ± 0·9 d (mean ± SEM) and platelets to greater than 100 × 10⁹/l in 17·5 ± 0·8 d. Four patients with acute myeloid leukaemia in complete remission received intensification with the supralethal combination of cyclophosphamide and total body irradiation followed by infusion of autologous marrow which had been stored at 4°C for 54 h. Haematological reconstitution in these patients was acceptable but slower (greater than 1·0 × 10⁹/l neutrophils between days 26 and 40; greater than 20 × 10⁹/l platelets between days 23 and 77). Except in one case, normal peripheral counts were attained in all patients.
It is concluded that bone marrow stored at 4°C for up to 54 h is a simple and practical source of viable stem cells which have the capacity for acceptable haematological reconstitution.     

Insurance,employment, and psychosocial consequences of a diagnosis of hereditary hemochromatosis in subjects without end organ damage

OBJECTIVES: Asymptomatic individuals with hereditary hemochromatosis (HH) may experience difficulties in obtaining employment or insurance, despite their good health. The extent to which these difficulties occur is unclear. The aim of this study was to assess the insurance, employment, and psychosocial consequences of a diagnosis of HH in subjects with no end organ damage. METHODS: In three outpatient clinics specializing in the treatment of HH, we performed a survey of individuals diagnosed with HH who were without end organ damage secondary to iron overload, along with their unaffected siblings. A review of the medical records of subjects with HH was performed. Main outcomes were attaining and keeping employment; health, disability and life insurance; and scores on the SF-36, a quality of life measure, and the SCL-90-R, a measure of psychological well-being. RESULTS: Of 130 eligible subjects with HH, 126 (97%) responded. Of the 55 eligible controls, 46 (84%) responded. Of the 126 subjects with HH, 25 (20%) described 28 incidents of insurance denial or increased premium rates, which they attributed to their diagnosis HH. Of the 28 incidents, 16 (57%) involved life insurance, eight (29%) involved health insurance, and four (14%) involved disability insurance. One subject reported an employment refusal. Five of the 25 subjects (20%) reporting insurance denial or increased premiums had significant comorbid conditions. One of 46 sibling controls (2%) reported an increased rate for life insurance (p = 0.003). No differences were noted in either the SF-36 or the SCL-90-R scores between subjects with HH and unaffected siblings. Overall rates of active health, disability, and life insurance were similar between the groups. CONCLUSIONS: Insurance denial and increased premium rates are reported commonly among individuals with HH without end organ damage. However, the overall proportion of those with active insurance, the quality of life, and the psychological well-being of these subjects were similar to those of unaffected siblings.     

Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure

The present studies were designed to determine the action of neutral endopeptidase inhibition (NEP-I), an inhibitor of the degradation of atrial natriuretic factor (ANF), in congestive heart failure (CHF). Studies were conducted in two groups of anesthetized dogs with CHF induced by 8 days of rapid right ventricular pacing. Group 1 (n = 5) received a specific NEP-I (SQ 28,603) at two doses administered sequentially -30 mg/kg followed by a 60 mg/kg i.v. bolus. Group 2 (n = 5) received intravenous infusion of exogenous ANF (100 ng/kg/min) to achieve increases in plasma ANF concentration as observed in group 1. NEP-I resulted in a diuresis and natriuresis (p less than 0.05) with increases in the fractional excretion of sodium and fractional excretion of lithium, the latter a marker for proximal tubule sodium delivery. Such tubular actions occurred in the absence of increases in glomerular filtration rate or renal blood flow but were associated with significant increases in urinary ANF and urinary cyclic GMP. Plasma ANF increased after the 30 mg/kg NEP-I dose. In contrast, in group 2 with exogenous ANF and despite a marked increase in plasma ANF, no natriuresis was observed. Arterial pressure did not change in either group. These studies demonstrate for the first time in CHF that NEP-I may potentiate the natriuretic action of endogenous ANF by a mechanism that is independent of systemic or renal hemodynamics and does not parallel increases in plasma ANF. These studies support an important therapeutic role for NEP-I in CHF.     

The beta cell glucose stimulus-response curve in normal humans assessed by insulin and C-peptide secretion rates

Insulin and C-peptide secretion rates have been measured and compared in 12 nondiabetic subjects to characterize the glucose stimulus-response of B cell secretion in man. On three different days, glucose concentrations were clamped for 150 minutes at 7.5, 10, and 15 mmol/L, respectively. Plasma samples taken during the clamps were assayed for C-peptide and insulin. C-peptide secretion rates were estimated by the technique of deconvolution. Model-based estimation of insulin secretion rates from insulin concentrations yielded concordant results. In response to glucose, C-peptide concentrations rose less quickly than did insulin concentrations, but the estimated first- and second-phase secretion rates were similar when assessed from either the C-peptide or insulin concentrations. First-phase secretion peaks were larger than inspection of the plasma concentration data might suggest, with median values of 1.3, 2.0, and 2.9 nmol/min for C-peptide in response to 7.5, 10, and 15 mmol/L glucose clamp levels, respectively. The second-phase reached steady state by 90 to 120 minutes, with median C-peptide secretion rates of 0.31, 0.56, and 0.85 nmol/min after 120 minutes at 7.5, 10, and 15 mmol/L, respectively. The slopes of the curves of steady-state insulin and C-peptide secretion rates v the four glucose levels (basal plus the three clamp levels) were maximally steep between 7.5 and 10 mmol/L in the majority of subjects, consistent with in vitro sigmoidal responses. A characterization of the secretory response of the B cell of normal humans at different glucose concentrations has been obtained. With appropriate models, insulin secretion rates may be estimated from either plasma insulin or C-peptide concentration data.     

Lower rather than higher levels of B-type natriuretic peptides (NT-pro-BNP and BNP) predict short-term mortality in end-stage heart failure patients treated with nesiritide

Elevated plasma natriuretic peptides in heart failure (HF) usually indicate a poor outcome and low levels a compensated state. In advanced chronic HF, however, low levels may reflect an impaired neurohormonal response. To assess this hypothesis, this study analyzed whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and B-type natriuretic peptide (BNP) levels were related to mortality in 40 patients treated for decompensated chronic HF. Cardiovascular mortality during follow-up (10 +/- 1 months) was 40%. BNP levels were lower in patients who died (487 +/- 60 vs 836 +/- 99 pg/ml, p <0.02), as were NT-pro-BNP levels (9,507 +/- 1,178 vs 17,611 +/- 4,338 pg/ml, p <0.05). These data support the hypothesis that patients with end-stage HF and poor short-term survival have lower natriuretic peptide levels than those who survive. These findings suggest that the natriuretic peptide system can no longer contribute adequately to neurohormonal compensation and that paradoxically low peptide levels are an adverse prognostic marker in advanced HF.     

Assessing mental imagery in clinical psychology: A review of imagery measures and a guiding framework

Mental imagery is an under-explored field in clinical psychology research but presents a topic of potential interest and relevance across many clinical disorders, including social phobia, schizophrenia, depression, and post-traumatic stress disorder. There is currently a lack of a guiding framework from which clinicians may select the domains or associated measures most likely to be of appropriate use in mental imagery research. We adopt an interdisciplinary approach and present a review of studies across experimental psychology and clinical psychology in order to highlight the key domains and measures most likely to be of relevance. This includes a consideration of methods for experimentally assessing the generation, maintenance, inspection and transformation of mental images; as well as subjective measures of characteristics such as image vividness and clarity. We present a guiding framework in which we propose that cognitive, subjective and clinical aspects of imagery should be explored in future research. The guiding framework aims to assist researchers in the selection of measures for assessing those aspects of mental imagery that are of most relevance to clinical psychology. We propose that a greater understanding of the role of mental imagery in clinical disorders will help drive forward advances in both theory and treatment.     

Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.     

On the role of intrinsic and extrinsic forces in early cardiac S‐looping

Background: Looping is a crucial phase during heart development when the initially straight heart tube is transformed into a shape that more closely resembles the mature heart. Although the genetic and biochemical pathways of cardiac looping have been well studied, the biophysical mechanisms that actually effect the looping process remain poorly understood. Using a combined experimental (chick embryo) and computational (finite element modeling) approach, we study the forces driving early s‐looping when the primitive ventricle moves to its definitive position inferior to the common atrium. Results: New results from our study indicate that the primitive heart has no intrinsic ability to form an s‐loop and that extrinsic forces are necessary to effect early s‐looping. They support previous studies that established an important role for cervical flexure in causing early cardiac s‐looping. Our results also show that forces applied by the splanchnopleure cannot be ignored during early s‐looping and shed light on the role of cardiac jelly. Using available experimental data and computer modeling, we successfully developed and tested a hypothesis for the force mechanisms driving s‐loop formation. Conclusions: Forces external to the primitive heart tube are necessary in the later stages of cardiac looping. Experimental and model results support our proposed hypothesis for forces driving early s‐looping. Developmental Dynamics 242:801–816, 2013. © 2013 Wiley Periodicals, Inc.