Randomised evaluation of the Italian medicines use review provided by community pharmacists using asthma as a model (RE I-MUR)

Background The Italian Ministry of Health decided to introduce community professional services in 2010. This trial provides an opportunity to evaluate the outcomes of a new professional pharmacy service: Italian Medicines Use Review (I-MUR) aimed at reducing the severity of asthma and its associated costs. Methods/Design This is a cluster randomised controlled trial of the I-MUR service. Data will be collected over time before, during and after pharmacists’ intervention. Fifteen Italian regions will be involved and it is aimed to recruit 360 community pharmacists and 1800 patients. Each pharmacist will receive training in medicines use review, recruit five patients, administer the Asthma Control Test and provide the I-MUR service. Pharmacists will be allocated to different groups, one group will be trained in and provide the I-MUR service immediately after completion of the baseline ACT score, the other group will receive training in the I-MUR and provide this service three months later. Group allocation will be random, after stratification by region of Italy. The I-MUR service will involve gathering data following each patient consultation including demographic details, patients regular medications, including those used for asthma, their attitude towards their medications and self-reported adherence to treatments. In addition, pharmacists will identify and record pharmaceutical care issues and any advice given to patients during the I-MUR, or recommendations given to doctors. Pharmacists will upload trial data onto a web platform for analysis. The primary outcome measure is the severity of asthma before, during and after the I-MUR assessed using the Asthma Control Test score. Secondary measures: number of all active ingredients used by patients during and after the I-MUR, number of pharmaceutical care issues identified during the I-MUR, patients’ self-reported adherence to asthma medication during and after the I-MUR, healthcare costs based on the severity of asthma, before, during and after the I-MUR service provision. Discussion This study has been developed because of the need for a new way of working for pharmacists and pharmacies; it is the first trial of any community pharmacy-based pharmaceutical care intervention in Italy. The results will inform future policy and practice in Italian community pharmacy. Trial registration number ISRCTN72438848. Keywords Asthma – Medicines use review – Cluster randomised controlled trial (RCT) – Community pharmac

Signs of oral dryness in relation to salivary flow rate, pH, buffering capacity and dry mouth complaints

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the signs of oral dryness in relation to different salivary variables and to correlate subjective complaints of oral dryness with salivary flow rate.</p> <p>Methods</p> <p>312 unmedicated healthy individuals belonging to three age groups, (6–11, 12–17, and 18–40 years) were examined clinically for signs of oral dryness. Resting and stimulated saliva were collected to determine flow rate, pH and buffering capacity. A questionnaire was used to obtain information on subjective sensation of dry mouth.</p> <p>Results</p> <p>Dry lip and dry mucosa were present in 37.5% and 3.2% of the sample respectively. The proportion of subjects who complained of oral dryness (19%) showed a stimulated salivary flow rate significantly lower than non complainers. Dry lip was significantly related to low resting flow rate but pH and buffering capacity did not show any significant relation to dry lip. Dry mucosa was not related to any of the above mentioned parameters.</p> <p>Conclusion</p> <p>The finding that the stimulated salivary flow rate was reduced in subjects complaining of dry mouth is of great clinical relevance, since the reduction is expected to be reflected in compromising various salivary functions.</p

A cluster randomised control trial to evaluate the effectiveness and cost-effectiveness of the Italian medicines use review (I-MUR) for asthma patients

Background The economic burden of asthma, which relates to the degree of control, is €5 billion annually in Italy. Pharmacists could help improve asthma control, reducing this burden. This study aimed to evaluate the effectiveness and cost-effectiveness of Medicines Use Reviews provided by community pharmacists in asthma. Methods This cluster randomised, multi-centre, controlled trial in adult patients with asthma was conducted in 15 of the 20 regions of Italy between September 2014 and July 2015. After stratification by region, community pharmacists were randomly allocated to group A (trained in and delivered the intervention at baseline) or B (training and delivery 3 months later), using computerised random number generation in blocks of 10. Each recruited up to five patients, with both groups followed for 9 months. The intervention consisted of a systematic, structured face-to-face consultation with a pharmacist, covering asthma symptoms, medicines used, attitude towards medicines and adherence, recording pharmacist-identified pharmaceutical care issues (PCIs). The primary outcome was asthma control, assessed using the Asthma-Control-Test (ACT) score (ACT ≥ 20 represents good control). Secondary outcomes were: number of active ingredients, adherence, cost-effectiveness compared with usual care. Although blinding was not possible for either pharmacists or patients, assessment of outcomes was conducted by researchers blind to group allocation. Results Numbers of pharmacists and patients enrolled were 283 (A = 136; B = 147) and 1263 (A = 600; B = 663), numbers completing were 201 (A = 97; B = 104) and 816 (A = 400; B = 416), respectively. Patients were similar in age and gender and 56.13% (458/816) had poor/partial asthma control. Pharmacists identified 1256 PCIs (mean 1.54/patient), mostly need for education, monitoring and potentially ineffective therapy. Median ACT score at baseline differed between groups (A = 19, B = 18; p < 0.01). Odds ratio for improved asthma control was 1.76 (95% CI 1.33–2.33) and number needed to treat 10 (95% CI 6–28). Number of active ingredients reduced by 7.9% post-intervention (p < 0.01). Adherence improved by 35.4% 3 months post-intervention and 40.0% at 6 months (p < 0.01). The probability of the intervention being more cost-effective than usual care was 100% at 9 months. Conclusions This community pharmacist-based intervention demonstrated both effectiveness and cost-effectiveness. It has since been implemented as the first community pharmacy cognitive service in Italy

Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation

Background: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. Results: All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Conclusions: Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication

Biology of human hair: Know your hair to control it

Hair can be engineered at different levels—its structure and surface—through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization

Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

We describe the concept of magnetic particle-scanning for on-chip detection of biomolecules: a magnetic particle, carrying a low number of antigens (Ag's) (down to a single molecule), is transported by hydrodynamic forces and is subjected to successive stochastic reorientations in an engineered magnetic energy landscape. The latter consists of a pattern of substrate-bound small magnetic particles that are functionalized with antibodies (Ab's). Subsequationuent counting of the captured Ag-carrying particles provides the detection signal. The magnetic particle-scanning principle is investigated in a custom-built magneto-microfluidic chip and theoretically described by a random walk-based model, in which the trajectory of the contact point between an Ag-carrying particle and the small magnetic particle pattern is described by stochastic moves over the surface of the mobile particle, until this point coincides with the position of an Ag, resulting in the binding of the particle. This model explains the particular behavior of previously reported experimental dose-response curves obtained for two different ligand-receptor systems (biotin/streptavidin and TNF-alpha) over a wide range of concentrations. Our model shows that magnetic particle-scanning results in a very high probability of irrununocomplex formation for very low Ag concentrations, leading to an extremely low limit of detection, down to the single molecule-per-particle level. When compared to other types of magnetic particle-based surface coverage assays, our strategy was found to offer a wider dynamic range (>8 orders of magnitude), as the system does not saturate for concentrations as high as 10(11) Ag molecules in a 5 mu L drop. Furthermore, by emphasizing the importance of maximizing the encounter probability between the Ag and the Ab to improve sensitivity, our model also contributes to explaining the behavior of other particle-based heterogeneous immunoassays