[The nurses' strike in the United Kingdom: the reasons, the debate and the implications]. / Lo sciopero degli infermieri nel Regno Unito: le ragioni, il dibattito e le implicazioni.

. The nurses' strike in the United Kingdom: an overview of the reasons, debate and implications. INTRODUCTION: In the UK, where the National Health Service (NHS) was founded, one of the most important and long-lasting strikes in nursing is taking place. AIM: To understand the historical, professional, political/social reasons for the UK nurse's strike. METHOD: Historical, scientific literature and data from key informant interviews have been analysed. Data has been summarized narratively. RESULTS: On 15th December 2022, more than 100,000 NHS nurses went on strike in England, Northern Ireland, and Wales asking for an increased salary; on the 6th and 7th of February and 1st of March the protest has continued. By improving pay, nurses believe the attractiveness of the profession can increase and counteract the loss of nurses who are leaving the public for the private sector, and the lack of attractiveness of the profession towards young people. The strike is organized by the Royal College of Nursing in a structured form which gives nurses precise information on how it should be explained to patients: according to a survey, 79% of the population supports the nurses' strike. However, not all agree with this strike action. DISCUSSION: The media, social media and professional debate is passionate with some polarization between who is in favor and who is against. Nurses strike not only for better wages but also to increase patient safety. What we see in the UK today is the result of years of austerity, lack of investment and health priorities: a similar situation experienced in several countries as well.

A methodology to assess the population size and estimate the needed resources for new licensed medications by combining clinical and administrative databases: The example of glycated haemoglobin in type 2 diabetes.

PURPOSE: To develop and validate a model to estimate glycated haemoglobin (HbA1c) values in patients with type 2 diabetes mellitus (T2DM) using a clinical data source, with the aim to apply this equation to administrative databases. METHODS: Using a primary care and administrative Italian databases, namely the Health Search database (HSD) and the ReS (Ricerca e Salute) database, we selected all patients aged 18 years or older on 31 December 2018 being diagnosed with T2DM and without prior prescription of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We included patients prescribed with and adherent to metformin. HSD was used to develop and test (using 2019 data as well) the algorithm imputing HbA1c values ≥7% according to a series of covariates. The algorithm was gathered by combining beta-coefficients being estimated by logistic regression models using complete case (excluding missing values) and imputed (after multiple imputation) dataset. The final algorithm was applied to ReS database using the same covariates. RESULTS: The tested algorithms were able to explain 17%-18% variation in assessing HbA1c values. Good discrimination (70%) and calibration were obtained as well. The best algorithm (three) cut-offs, namely those providing correct classifications ranging 66%-70% was therefore calculated and applied to ReS database. By doing so, from 52 999 (27.9, 95% CI: 27.7%-28.1%) to 74 250 (40.1%, 95% CI: 38.9%-39.3%) patients were estimated with HbA1c ≥7%. CONCLUSION: Through this methodology, healthcare authorities should be able to quantify the population eligible to a new licensed medication, such as SGLT-2 inhibitors, and to simulate scenarios to assess reimbursement criteria according to precise estimates.

Estudo comparativo com microscópio a laser confocal da superfície do esmalte após a aplicação de diferentes técnicas de remoção do material de adesão dos bráquetes / Comparative study with confocal laser microscopy of the enamel surface after the application of different techniques for removing the adhesion material from the brackets

Resumo O objetivo desta pesquisa foi avaliar e quantificar a rugosidade do esmalte dentário após a remoção do adesivo residual ao retirar os bráquetes. Em 30 pré-molares humanos clinicamente saudáveis, foi realizada a colagem de bráquetes no centro da face vestibular. Após 24 horas, foram descolados e foi realizado o polimento do adesivo residual com três métodos diferentes: fresa multilaminada (12 lâminas) tronco-cônico com instrumentos rotativos em alta velocidade irrigada com água; fresa redonda com instrumentos rotativos em baixa velocidade (contra ângulo) sem irrigação e fresa de fibra de vidro com instrumentos rotativos em baixa velocidade (contra-ângulo) sem irrigação. Os elementos dentários foram observados com microscópio laser confocal antes da colagem dos bráquetes. Após a sua retirada e remoção do adesivo residual, a superfície do esmalte foi observada novamente com o microscópio laser confocal, e foi utilizado o software digital OLYMPUS OLS-4100 para realizar uma reconstrução tridimensional e medir a rugosidade deixada pelos diferentes métodos de polimento. Os resultados indicaram que a fresa multilaminada em alta velocidade irrigada com água é a que deixa a superfície com parâmetros de rugosidade mais baixos. Portanto, a fresa multilaminada seria o método mais indicado para eliminar a resina residual após a retirada dos bráquetes ao final de um tratamento ortodôntico (AU)

Abstract The aim of this research was to evaluate and quantify the roughness of the dental enamel after removing the residual adhesive when removing the brackets. In 30 clinically healthy human premolars, brackets were bonded in the center of the buccal face, which were detached in 24 hours, and the residual adhesive was polished with three different methods: multi-laminated bur (12 blades) conical trunk with rotary instruments in high speed irrigated with water, round milling cutter with low-speed rotary instruments (contra-angle) without irrigation, and glass milling (Fiber Glass) with low-speed rotary instruments (contra-angle) without irrigation. The dental elements were observed with a confocal laser microscope before bracket bonding. After its removal and removal of the residual adhesive, the enamel surface was observed again with the confocal laser microscope, and the OLYMPUS OLS-4100 digital software was used to perform a three-dimensional reconstruction and measure the roughness left by the different polishing methods. The results indicated that the multi-laminated cutter at high speed, irrigated with water, is the one that leaves the surface with lower roughness parameters. Therefore, the multilaminated bur would be the most suitable method to eliminate residual resin after removing brackets at the end of an orthodontic treatment. (AU)

Technical Note: RNA Extraction Alternative Method for SARS-CoV-2 Molecular Diagnosis.

The devastating COVID-19 outbreak posed serious challenges for the diagnostics laboratories, facing global shortage of reagents and equipment. This study aimed at evaluating an additional RNA extraction method respect to those already recommended by WHO and CDC. A new protocol for RNA extraction from nasopharyngeal swab was set up, adapting a Qiagen kit, and validated on a set of 96 clinical samples. The analysis showed a sensitivity of 94% and a specificity of 97%, but considering samples with Ct<36.5, the sensitivity and the specificity increased to 100%. The adapted method was also able to detect samples with very low viral load (Ct>38), indicating that the two approaches can be considered equivalent for the SARS-CoV-2 diagnostics. This extraction method can help in increasing the throughput for SARS-CoV-2 molecular test, even in a low automation setting.

Differential Analysis of Gly211Val and Gly286Val Mutations Affecting Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA1) in Congenital Pseudomyotonia Romagnola Cattle.

Congenital pseudomyotonia in cattle (PMT) is a rare skeletal muscle disorder, clinically characterized by stiffness and by delayed muscle relaxation after exercise. Muscle relaxation impairment is due to defective content of the Sarco(endo)plasmic Reticulum Ca2+ ATPase isoform 1 (SERCA1) protein, caused by missense mutations in the ATP2A1 gene. PMT represents the only mammalian model of human Brody myopathy. In the Romagnola breed, two missense variants occurring in the same allele were described, leading to Gly211Val and Gly286Val (G211V/G286V) substitutions. In this study, we analyzed the consequences of G211V and G286V mutations. Results support that the reduced amount of SERCA1 is a consequence of the G211V mutation, the G286V mutation almost being benign and the ubiquitin-proteasome system (UPS) being involved. After blocking the proteasome using a proteasome inhibitor, we found that the G211V mutant accumulates in cells at levels comparable to those of WT SERCA1. Our conclusion is that G211/286V mutations presumably originate in a folding-defective SERCA1 protein, recognized and diverted to degradation by UPS, although still catalytically functional, and that the main role is played by G211V mutation. Rescue of mutated SERCA1 to the sarcoplasmic reticulum membrane can re-establish resting cytosolic Ca2+ concentration and prevent the appearance of pathological signs, paving the way for a possible therapeutic approach against Brody disease.

Development and internal validation of a prognostic model for 15-year risk of Alzheimer dementia in primary care patients.

BACKGROUND: The exploitation of routinely collected clinical health information is warranted to optimize the case detection and diagnostic workout of Alzheimer's disease (AD). We aimed to derive an AD prediction score based on routinely collected primary care data. METHODS: We built a cohort selecting 199,978 primary care patients 60 + part of the Health Search Database between January 2002 and 2009, followed up until 2019 to detect incident AD cases. The cohort was randomly divided into a derivation and validation sub-cohort. To identify AD and non-AD cases, we applied a clinical algorithm that involved two clinicians. According to a nested case-control design, AD cases were matched with up to 10 controls based on age, sex, calendar period, and follow-up duration. Using the derivation sub-cohort, 32 potential AD predictors (sociodemographic, clinical, drug-related, etc.) were tested in a logistic regression and selected to build a prediction model. The predictive performance of this model was tested on the validation sub-cohort by mean of explained variation, calibration, and discrimination measurements. RESULTS: We identified 3223 AD cases. The presence of memory disorders, hallucinations, anxiety, and depression and the use of NSAIDs were associated with future AD. The combination of the predictors allowed the production of a predictive score that showed an explained variation (pseudo-R2) for AD occurrence of 13.4%, good calibration parameters, and an area under the curve of 0.73 (95% CI: 0.71-0.75). In accordance with this model, 7% of patients presented with a high-risk score for developing AD over 15 years. CONCLUSION: An automated risk score for AD based on routinely collected clinical data is a promising tool for the early case detection and timely management of patients by the general practitioners.

Patterns of oral corticosteroids use in primary care patients with severe asthma.

AIM: To assess the pattern of use of oral corticosteroids (OC) in primary care patients with severe asthma. METHODS: Data derived from the Health Search Database (HSD) gathering information on 700 Italian general practitioners. A cohort of severe asthma patients was identified between 2013 and 2017 and followed-up for one year. The association between candidate predictors and the incident escalation to OC was tested through a multivariate Cox regression model. RESULTS: Among patients with asthma (N = 55,075), 284 were diagnosed with severe asthma. Among them, the proportion of OC users decreased from 82.2% in 2013 to 75.3% in 2017. For what concerns the determinants of OC prescriptions, among 284 patients being defined at baseline (2013-2016) as those suffering from severe asthma, 216 (76.1%) were first-ever prescribed with OC at least once during one year of follow-up. The presence of gastroesophageal reflux disease (HR 1.37; 95% CI 1.02-1.85), osteoarthritis (HR 1.54; 95% CI 1.12-2.12) and moderate asthma exacerbations (HR 1.72; 95% CI 1-02-2.93) was significantly associated with the outcome. CONCLUSIONS: The optimization of asthma treatment and the management of comorbidities may be potential leverages to reduce the inappropriate use of OC in patients with severe asthma.

Adherence to COPD free triple inhaled therapy in the real world: a primary care based study.

INTRODUCTION: The development of new pharmacological treatments for chronic obstructive pulmonary disease (COPD) has improved health-related quality of life of patients. However, suboptimal adherence may limit its potential. OBJECTIVE: The aim of the present study was to assess the adherence to free triple inhaled therapy and to investigate poor adherence determinants among primary care patients. METHODS: Data were derived from a primary care database in Italy. Patients aged 40+ affected by COPD and prescribed with inhaled corticosteroids, long-acting beta agonists and long-acting muscarinic antagonists (N = 3177) were enrolled. Low adherence was defined as a proportion of days covered (PDC) by medications prescription lower than 80%. Predictors of low adherence were tested using logistic regression models. RESULTS AND CONCLUSIONS: The 85% of enrolled patients showed poor adherence to free triple inhaled therapy. Comorbidities, such as heart failure (OR 1.78, 95%CI 1.19-2.75), depression (OR 1.41, 95%CI 1.06-1.88) and peripheral vascular disease (OR 1.32, 95%CI 1.01-1.74) were associated with poor adherence. Former (OR 0.52, 95%CI 0.34-0.78) or current smokers (OR 0.61, 95%CI 0.41-0.93) and patients with more severe airways obstruction or history of severe exacerbations (OR 0.64, 95%CI 0.52-0.79) were less likely to exhibit poor adherence. Real-world adherence to triple inhaled therapy with different inhalers is generally low. Higher GOLD airways obstruction stage and current or former smoking status are associated with increased adherence to treatment. Reduced perceived benefit on symptoms control is probably linked to poorer adherence to free triple therapy.

Triple inhaled therapy in COPD patients: determinants of prescription in primary care.

OBJECTIVE: To assess the incidence and determinants of the triple inhaled therapy in chronic obstructive pulmonary disease (COPD) primary care patients. METHODS: Data derived from the Health Search Database (HSD) gathering information on 700 Italian general practitioners. A cohort of COPD patients, prescribed for the first time with inhaled treatments, was followed-up between January 2002 and December 2014. The outcome was the first incident prescription of a triple inhaled therapy, namely the combination of inhaled corticosteroids (ICS), long-acting beta agonists (LABA), and long-acting muscarinic antagonists (LAMA). Cox regressions were used to test the association (hazard ratios, HR) between candidate determinants and the outcome. RESULTS: Out of 17589 patients (mean age 71.1 ±â€¯11.3 years; 37.4% females), 3693 (21%) were prescribed with a triple inhaled therapy during follow-up. Older age (HR = 1.79 to 2.61), current and former smoking habit (HR = 1.72 and 1.66), higher GOLD stage (HR = 1.45 to 2.79), the number of moderate and severe COPD exacerbations (HR = 1.10 to 2.63), and heart failure (HR = 1.17) resulted statistically significantly associated with an increased incident prescription of the triple inhaled therapy. Female sex (HR = 0.80) and some comorbidities (HR = 0.21 to 0.87) resulted negatively associated with the outcome. Furthermore, patients initially treated with LAMA (HR = 1.5) and LABA/ICS (HR = 1.23) were more likely to escalate to the triple therapy, than those on LABA. Conversely, patients initially treated with ICS presented a negative hazard (HR = 0.72). CONCLUSIONS: The knowledge of demographic and clinical determinants of the escalation to the triple inhaled therapy in real-world COPD patients may help clinicians to better personalize respiratory pharmacological treatments of their patients, and inform international societies that issue clinical guidelines.

Methadone Dose Adjustments, Plasma R-Methadone Levels and Therapeutic Outcome of Heroin Users: A Randomized Clinical Trial.

AIMS: We aimed to improve the retention in treatment and therapeutic outcome of methadone maintenance treatment (MMT) patients by adjusting the oral methadone dose in order to reach a "target" plasma R-methadone level (80-250 ng/mL). METHODS: A multicenter randomized controlled trial was organized. RESULTS: The intention-to-treat statistical analysis showed that repeated dose adjustments performed in order to obtain therapeutic plasma R-methadone levels did not improve retention in treatment of heroin-dependent patients. However, patients having plasma methadone levels in the "target range" at the beginning of the study had a better retention in treatment than controls. Furthermore, patients succeeding in keeping plasma R-methadone target levels (per protocol analysis) remained in treatment and improved their social scores better than controls. -Conclusion: Although the primary endpoint of this study was not demonstrated, a post hoc and a per protocol analysis suggested that patients in MMT with plasma R-methadone concentrations in the target range have a better therapeutic outcome than controls.

Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for limb-girdle muscular dystrophy 2D.

Limb-girdle muscular dystrophy type 2D (LGMD2D) is a rare autosomal-recessive disease, affecting striated muscle, due to mutation of SGCA, the gene coding for α-sarcoglycan. Nowadays, more than 50 different SGCA missense mutations have been reported. They are supposed to impact folding and trafficking of α-sarcoglycan because the defective polypeptide, although potentially functional, is recognized and disposed of by the quality control of the cell. The secondary reduction of α-sarcoglycan partners, ß-, γ- and δ-sarcoglycan, disrupts a key membrane complex that, associated to dystrophin, contributes to assure sarcolemma stability during muscle contraction. The complex deficiency is responsible for muscle wasting and the development of a severe form of dystrophy. Here, we show that the application of small molecules developed to rescue ΔF508-CFTR trafficking, and known as CFTR correctors, also improved the maturation of several α-sarcoglycan mutants that were consequently rescued at the plasma membrane. Remarkably, in myotubes from a patient with LGMD2D, treatment with CFTR correctors induced the proper re-localization of the whole sarcoglycan complex, with a consequent reduction of sarcolemma fragility. Although the mechanism of action of CFTR correctors on defective α-sarcoglycan needs further investigation, this is the first report showing a quantitative and functional recovery of the sarcoglycan-complex in human pathologic samples, upon small molecule treatment. It represents the proof of principle of a pharmacological strategy that acts on the sarcoglycan maturation process and we believe it has a great potential to develop as a cure for most of the patients with LGMD2D.

Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care.

PURPOSE: Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug-drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations. METHODS: By using the Italian general practice Health Search Database (HSD), we retrospectively selected adult patients with at least one LT4 prescription from 2012 to 2015 and at least 1 year of clinical history recorded. The incident prescription of interacting medications (e.g., proton pump inhibitors, calcium or iron salts) was the index date. Analysis was carried out using a self-controlled study design. RESULTS: Overall, 3965 users of LT4 formed the study cohort (84.1% women, mean age 56 ± 16.5 years). TSH variability on the entry date was greater among liquid LT4 users than in those prescribed with tablets as shown by the difference between 75th and 25th centile, which were 3.01 and 3.8, respectively. The incidence rate ratio (IRR) for TSH variability did not differ between groups, before and during exposure to DDIs. In contrast, PDDs less likely increased during the exposure to DDI with oral liquid LT4 compared with tablets (IRR = 0.84; 95% CI: 0.77-0.92), especially in patients with post-surgical hypothyroidism (IRR = 0.75; 95% CI: 0.64-0.85). CONCLUSIONS: In clinical practice, the use of oral liquid LT4 is not associated with increased PDDs, compared with tablets formulation, during exposure to DDIs. These results support the need for individualizing LT4 formulation to prescribe, especially in patients with various comorbidities and complex therapeutic regimens.

Poor adherence to chronic obstructive pulmonary disease medications in primary care: Role of age, disease burden and polypharmacy.

AIM: The aim of the present study was to assess the occurrence and determinants of poor adherence to pharmacological treatment in a cohort of primary care patients with chronic obstructive pulmonary disease (COPD), paying special attention to the role of age, comorbidity and polypharmacy. METHODS: We identified a cohort of COPD patients using the primary care Italian Health Search - IMS Longitudinal Patient Database. We assessed 1-year adherence to COPD maintenance pharmacotherapy (encompassing inhaled corticosteroids, long-acting beta agonists and long-acting anticholinergics). Poor adherence was defined as <80% of proportion of days covered by pharmacological treatment over a 1-year period. RESULTS: Of 22 505 patients (mean age 67.3 ± 13.2; 41.3% women) entering the study, 17 486 (77.7%) were poorly adherent. According to multivariate analysis, poor adherence is less likely in older adults (OR 0.51, 95% CI 0.40-0.66), in non-smokers (OR 0.77, 95% CI 0.69-0.86) and in those with a history of alcohol abuse (OR 0.74, 95% CI 0.58-0.94). Higher comorbidity (OR 1.43, 95% CI 1.13-1.80) was positively associated with poor adherence. Polypharmacy was associated with poor adherence only in patients aged ≥65 years (OR 1.34, 95% CI 1.13-1.59). Finally, COPD severity was associated with a reduced likelihood of poor adherence (OR 0.20, 95% CI 0.07-0.61 for stage IV). CONCLUSIONS: The present findings show that poor medication adherence is common in patients with COPD receiving long-term treatment. The interaction between age and polypharmacy, and the role of comorbidity suggest a pivotal role of biological age as a steering determinant of poor adherence. Geriatr Gerontol Int 2017; 17: 2500-2506.

Variability of adverse events in the public health-care service of the Tuscany region.

The objective of the study is to analyze the variation of adverse events (AEs) according to the different structure of hospitals. The study is a multicenter, retrospective study. It involves 4 teaching hospitals (THs) and 32 community hospitals, distributed in 12 local trusts (LTs), of the Tuscany Regional Healthcare Service (RHS). A random sample of the clinical records of patients admitted in LTs and THs in 2008 was selected from the database of the hospital discharge records of the centers. Among 11,293 clinical records included, a total of 354 adverse events were identified. There was a significant higher incidence of AEs in the male and elderly (>65 years) population, and the incidence of AEs was more relevant in the THs (5.3, 95% CI 4.7-6.1) than in the LTs (1.8, 95% CI 1.5-2.2). AEs related to falls were significantly more preventable in THs (OR 19.22, 95% CI 2.45-151.02), while in LTs, AEs related to infections were the most preventable (OR 6.22, 95% CI 1.35-28.67). Concerning the consequence of AE, death is significantly more probable for AEs related to unexpected cardiac arrest in LTs, while disability and prolongation of the stay are significantly more probable consequences associated with re-admission in THs, and to transfer to ICU or HDU in LTs. Re-interventions, surgical complications and falls are the factors more correlated with AEs. In conclusion, the study shows a higher risk of incurring adverse events for the THs compared to the LTs, presumably connected with a major complexity of the clinical cases. Furthermore, the preventability of AEs is higher in the LTs (56.1 vs 42.2%), and this might be associated with lower expertise in managing complications in these settings. Concerning specialties, there are no significant differences in AEs distribution.

Type 2 Diabetes Mellitus Treatment Patterns Across Europe: A Population-based Multi-database Study.

PURPOSE: The aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. METHODS: Prescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns. FINDINGS: A total of 253,530 patients initiating T2DM treatment during the study period were included; 52% to 55% were male, and the mean age ranged from 62 to 67 years. Metformin was the most common initial treatment in all countries. After initial therapy, most patients in the Netherlands, Spain, and the United Kingdom switched to a combination of metformin + a sulfonylurea derivative (SU). In Italy, metformin in combination with an SU was outnumbered by "other treatment," mainly because of repaglinide use. In France, treatments including dipeptidyl peptidase-4 inhibitors were most frequent as second- and fourth-line treatment. Metformin monotherapy was again most commonly observed as the third line of treatment in all countries. Fourth treatment was a combination of metformin + an SU in the Netherlands and Spain; in the United Kingdom and France, dipeptidyl peptidase-4 inhibitors were the most frequently used fourth line of treatment. IMPLICATIONS: This study provides a comprehensive overview of T2DM treatment patterns among patients initiating T2DM treatment in 5 European countries. There were differences, especially regarding the uptake of newer incretin-based treatments, which are usually prescribed as a second and/or third treatment in agreement with local guidelines. These variations reflect the differences between the national guidelines of these countries.

Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners' electronic medical records: a validation study.

OBJECTIVES: The Italian project MATRICE aimed to assess how well cases of type 2 diabetes (T2DM), hypertension, ischaemic heart disease (IHD) and heart failure (HF) and their levels of severity can be automatically extracted from the Health Search/CSD Longitudinal Patient Database (HSD). From the medical records of the general practitioners (GP) who volunteered to participate, cases were extracted by algorithms based on diagnosis codes, keywords, drug prescriptions and results of diagnostic tests. A random sample of identified cases was validated by interviewing their GPs. SETTING: HSD is a database of primary care medical records. A panel of 12 GPs participated in this validation study. PARTICIPANTS: 300 patients were sampled for each disease, except for HF, where 243 patients were assessed. OUTCOME MEASURES: The positive predictive value (PPV) was assessed for the presence/absence of each condition against the GP's response to the questionnaire, and Cohen's κ was calculated for agreement on the severity level. RESULTS: The PPV was 100% (99% to 100%) for T2DM and hypertension, 98% (96% to 100%) for IHD and 55% (49% to 61%) for HF. Cohen's kappa for agreement on the severity level was 0.70 for T2DM and 0.69 for hypertension and IHD. CONCLUSIONS: This study shows that individuals with T2DM, hypertension or IHD can be validly identified in HSD by automated identification algorithms. Automatic queries for levels of severity of the same diseases compare well with the corresponding clinical definitions, but some misclassification occurs. For HF, further research is needed to refine the current algorithm.

[Correction: Adverse events and preventable consequences: retrospective study in five large Italian hospitals]. / Correzione: Eventi avversi e conseguenze prevenibili: studio retrospettivo in cinque grandi ospedali italiani.

[This corrects the Table 4 of the article: pmid: 22828228].

Development and Validation of a Score for Adjusting Health Care Costs in General Practice.

OBJECTIVE: To develop and validate the Italian Health Search Morbidity (HSM) Index to adjust health care costs in general practice. METHODS: The study population comprised 1,076,311 patients registered in the Health Search CSD Longitudinal Patient Database between January 1, 2008, and December 31, 2010. We randomly selected 538,254 and 538,057 patients to form the development and validation cohorts, respectively. To ensure model convergence, 5% of the aforementioned cohorts were selected randomly to create development and validation samples. The outcome was the total direct health care costs covered by the national health system. Interaction between age and sex, chronic diseases, and acute diseases were entered in a multilevel generalized linear latent mixed model with random intercepts (province of residence and general practitioner) to identify determinants associated with increased or decreased costs. The estimated coefficients were linearly combined to create the HSM Index for individual patients. The score was applied to the validation sample, and measures of predictive accuracy, explained variance, and the observed/predicted ratio were computed to evaluate the model's accuracy. RESULTS: The mean yearly cost was €414.57 per patient, and the HSM Index had a median value of 5.08 (25th-75th range 4.44-5.98). The HSM Index explained 50.17% of the variation in costs. Concerning calibration, in 80% of the population, the margin of error in the estimation of costs was around 10%. CONCLUSIONS: The HSM Index is a reliable case-mix system that could be implemented in general practice for costs adjustment. This tool should ensure fairer scrutiny of resource use and allocation of budgets among general practitioners.

Drug interactions with levothyroxine therapy in patients with hypothyroidism: observational study in general practice.

BACKGROUND AND OBJECTIVES: Several drugs may interact with levothyroxine and reduce its bioavailability. The aim of this study was to analyse the Italian general practice patients with hypothyroidism from 2002-2011, in terms of variation of thyroid-stimulating hormone (TSH) levels, number of levothyroxine prescriptions and dose of levothyroxine before and during potential drug-drug interactions (DDIs). METHODS: Data were extracted from the Italian general practice Health Search CSD Longitudinal Patient Database (HSD). Analysis was limited to individuals aged 18 years and older with at least one levothyroxine prescription from 2002 to 2011 and at least one year of clinical history recorded in HSD. A quasi-experimental pre-post analysis was carried out using a self-controlled study design, on an intention-to-treat basis. RESULTS: Overall, 5,426 levothyroxine users (7.5 % of population in HSD) were included in the study. The incidence rate ratio comparing the TSH trend before and during the period of exposure to potential DDI showed a significant increase of TSH levels during initial exposure to potential DDI, which decreased over time. The number of prescriptions and dose of levothyroxine decreased before the potential DDI and increased symmetrically during the period of exposure to potential DDI. CONCLUSIONS: The co-prescription of levothyroxine and potentially interacting drugs results in an increased use of levothyroxine. Clinicians should carefully consider adjusting levothyroxine therapy in presence of concomitant drugs, such as proton-pump inhibitors, which may reduce levothyroxine bioavailability.