What drives inhaler prescription for asthma patients? Results from a real-life retrospective analysis.

BACKGROUND: The choice of inhaler device for asthma patients depends upon multiple attributes. We investigated factors that may drive general practitioners (GPs) and respiratory specialists in the prescription of inhaler devices for asthma patients who initiated inhalation therapy. METHODS: We retrospectively analysed prescriptions by GPs and respiratory specialists to asthma patients commencing inhaled corticosteroid/long-acting ß2-agonist combination therapy available as both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Patient characteristics were compared by device and multivariate analysis was used to model the likelihood of receiving a pMDI as opposed to a DPI in order to identify drivers for prescription. A sample of the respiratory specialists completed an ad-hoc survey of their perceived success in achieving asthma control in their patients and barriers to attaining full control. RESULTS: Prescription of a particular inhaler device was unrelated to the characteristics of the patients. Multivariate analysis revealed that the main driver for the choice of inhaler device was the medication (Odds Ratio and 95% Confidence Interval, respectively for GPs and specialists: 0.19 [0.16-0.23]; 0.17 [0.08-0.37]). Specialists perceived asthma as being inadequately controlled in 41% of their patients, and considered patients' difficulties in using DPIs and pMDIs as instrumental in this, citing a need for a novel, more effective inhaler technology. CONCLUSION: Physicians choose inhaler devices according to the prescribed drugs and not to the characteristics of the individual patient. This may reflect a lack of confidence in existing inhaler devices and underlines the need for technologies, which are more reliable and easier to use by patients.

Medication and breastfeeding.

It is well accepted that the best feeding method for infants is breastfeeding, due to its numerous biological and clinical effects on child and maternal health. The use of medication by the nursing mother and the physician's advice to stop nursing are the most common reasons for the cessation of breastfeeding. The physician plays an extremely delicate role and should be able to assess risks and benefits for both mother and child. The main factors that must be taken into account include pharmacokinetics, the duration of maternal therapy, the age of the infant and the general health of the infant. All physicians should have access to reliable and updated information on medication safety during breastfeeding (reference books, online medical literature). Few drugs have been demonstrated to be absolutely contraindicated during breastfeeding. Nevertheless clear, safe and reliable information is still lacking for most drugs and it would be desirable to improve the knowledge about mechanisms and consequences of infant exposure to drug present in milk.

Hyperbilirubinemia and management of breastfeeding.

Hyperbilirubinemia and jaundice are natural, physiological phenomena which are only to be expected in the neonatal period, within certain limits. The highest percentage of jaundice in breastfed newborns should be evaluated in connection with inadequate management of breastfeeding rather than a direct effect of breast milk. Breastfeeding is also linked to visible jaundice persisting beyond the first two weeks of life (“breast milk jaundice”), but the appearance of skin jaundice is not a reason for interrupting breastfeeding which can and should continue without any interruption in most cases. There have been numerous contributions to the literature which have rescaled the direct role of breast milk both in early jaundice and in the more severe cases of late jaundice. The reviewed guidelines for detection and management of hyperbilirubinemia underline how prevention of badly managed breastfeeding and early support for the couple mother-child are effective prevention measures against severe early-onset jaundice; furthermore, the breastfeeding interruption is no longer recommended as a diagnostic procedure to identify breast milk jaundice because of its low specificity and the risk to disregarding the detection of a potentially dangerous disease.

Is breastfeeding duration influenced by maternal attitude and knowledge? A longitudinal study during the first year of life.

OBJECTIVE: To discuss the duration and types of breastfeeding and to identify the factors associated with the early introduction of formula milk. MATERIALS AND METHODS: This longitudinal study was conducted in the largest birthing centre of Turin. 562 mother-infant pairs were selected randomly and enrolled from among all the births that occurred in our Hospital from January to December 2009. Data was collected by means of a questionnaire filled out by the researcher during a face-to-face interview at mother's bed side during her hospital stay. This questionnaire included data regarding maternal socio-demographic, biomedical and hospital-related characteristics and some questions regarding family support, maternal attitude and current knowledge on breastfeeding. Mothers were interviewed by telephone at 1, 3, 6 and 12 months postpartum using the 24-h recall technique and definitions recommended by the WHO to investigate the type of breastfeeding adopted. RESULTS: At the age of 6 months only 8.9% of the infants involved were still exclusively breastfed and 44.3% had discontinued breastfeeding. By the age of 12 months 25.3% of infants were still receiving some breast milk. The main factors that had a negative impact on the duration of breastfeeding included maternal smoking habits, early pacifier introduction and the maternal infant feeding attitude. CONCLUSIONS: The rate of initiation and overall duration of breastfeeding reached the WHO objectives, but exclusive breastfeeding duration has still not reached satisfactory levels at 6 months. Given that the maternal infant feeding attitude is the only factor independently related to breastfeeding duration for the whole first year of life, reliable measures of maternal attitude could be used as a first step in targeting and assessing interventions that promote and sustain breastfeeding.

Drugs and breastfeeding: instructions for use.

It's universally well known that breastfeeding, due to its numerous beneficial effects on child and maternal health, is the best feeding method for infants. The use of medication by the nursing mother and the physician's advice to stop nursing are the most common reasons for the cessation of breastfeeding. The physician plays an extremely delicate role and should be able to assess risks and benefits for both mother and child. The issue of which drugs are safe to take during lactation is quite complicated. Three main factors must be taken into account: pharmacokinetics, assessment of the risk to the infant and to the lactation. Excellent sources of reliable information are the reference books. For the most up-to-date information it would be useful to consult the online medical literature. Few drugs have been demonstrated to be absolutely contraindicated during breastfeeding. Clear, safe and reliable information is still lacking for most drugs. It would be desirable to see an improvement in knowledge about mechanisms for transfer of drugs into milk, to analyze the biotransformation process for a given drug and to study the clinical consequences of infant exposure to drugs present in milk.

Anti-tumor necrosis factor alpha therapy normalizes fibrinolysis impairment in patients with active rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk and involvement of inflammation, coagulation and fibrinolysis. Treatment with infliximab, a tumour necrosis factor-alpha (TNF-alpha) blocking chimeric monoclonal antibody, induces a long-term reduction of inflammation and coagulation, but its effect on fibrinolysis is still unknown. We carried out an observational study investigating plasma biomarkers of inflammation and fibrinolysis in RA patients before and after 14 weeks of infliximab treatment given according to the therapeutic guidelines for RA. METHODS: We studied 20 selected patients with active RA and without any other atherosclerosis risk factor as well as 40 healthy controls. Patients, treated with a stable dose of methotrexate, received infliximab (3 mg/kg) at week 0, 2, 6 and 14. At week 0 and 14, we assessed clinical, inflammatory and fibrinolyitic parameters. RESULTS: At baseline, plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity and tissue-type plasminogen activator (t-PA) antigen were significantly higher in RA patients than in controls (p=0.01, p=0.001 and p=0.0001 respectively). After 14 weeks of infliximab treatment, the levels of PAI-1 antigen, PAI-1 activity and t-PA antigen significantly decreased till normalization (p=0.0001). Plasma levels of C reactive protein (CRP) and interleukin-6 (IL-6) were directly correlated with levels of PAI-1 antigen (p=0.011 and p=0.0001), PAI-1 activity (p=0.013 and p=0.027) and t-PA antigen (p=0.017 and p=0.040). CONCLUSIONS: This study provides evidence that TNF-alpha blockade by infliximab not only decreases inflammation, but also reduces the inhibition of fibrinolysis. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.

[Nailfold capillaroscopic report: qualitative and quantitative methods]. / La refertazione dell'esame capillaroscopico: metodi di valutazione qualitativi e quantitativi.

Nailfold capillaroscopy (NVC) is a simple and non-invasive method used for the assessment of patients with Raynaud's phenomenon (RP) and in the differential diagnosis of various connective tissue diseases. The scleroderma pattern abnormalities (giant capillaries, haemorrages and/or avascular areas) have a positive predictive value for the development of scleroderma spectrum disorders. Thus, an analytical approach to nailfold capillaroscopy can be useful in quantitatively and reproducibly recording various parameters. We developed a new method to assess patients with RP that is capable of predicting the 5-year transition from isolated RP to RP secondary to scleroderma spectrum disorders. This model is a weighted combination of different capillaroscopic parameters (giant capillaries, microhaemorrages, number of capillaries) that allows physicians to stratify RP patients easily using a relatively simple diagram to deduce prognosis.

Primary antiphospholipid syndrome associated with small aorta syndrome: a case report.

It has been widely accepted that the antiphospholipid syndrome (APS) is an autoimmune hypercoagulability syndrome in which a variety of venous and arterial thrombotic events may occur. Peripheral obliterating arterial disease characterized by aortoiliac steno-occlusion occurring in young women, is reported in the literature under the name of Small Aorta Syndrome (SAS). Although it remains unclear whether SAS represents a separate entity, the small size of the distal aorta increases the risk for aortoiliac occlusive disease. A 41-year old white woman was admitted with acute digital ischemia of the left foot. She had positive lupus anticoagulant and IgG anti-cardiolipin antibodies (61 UI/mL), but antinuclear antibodies and anti-ds-DNA antibodies were negative. She previously had two deep venous thromboses of the legs and, despite the oral anticoagulant therapy, pulmonary embolism occurred. Shortly thereafter, abdominal angio-magnetic resonance imaging suggested that the infra-renal aorta was narrowed more than 50%, without thrombotic occlusion of the terminal aorta and common iliac arteries. These findings were compatible with the features of SAS. There were no atherosclerotic changes in the artery wall and no other prediposing risk factors such as smoking, oral contraceptive or hyperlipidemia. After adequate anticoagulation and intravenous prostacyclin treatment the patient's symptoms and the ischemic lesions improved markedly. To our knowledge this is the first report of the association of SAS and primary APS. The occurrence of SAS in patients with APS may dramatically increase the risk of trombothic events.

[Cost-of-illness in systemic sclerosis: a retrospective study of an Italian cohort of 106 patients]. / Analisi dei costi nella sclerosi sistemica. Studio retrospettivo in una casistica di 106 pazienti.

AIMS: It is increasingly important to determine the economic consequences of diseases considering the policy of limited health-care budgets. In this study we evaluated the annual direct and indirect costs of Systemic Sclerosis (SSc) and we tried also to identify any cost predictors. METHODS: We studied 106 patients (103 female, 3 male), 57 affected by Limited Systemic Sclerosis (LSSc) and 49 affected by Diffuse Systemic Sclerosis (DSSc). Mean age was 57 years (SD +/- 13.8) and mean disease duration was 8,9 years (SD +/- 7.2). Direct Costs: data were calculated referring to DRG (Disease Related Group) expenses for the in-patients. We referred to national pharmacopoeia to calculate the pharmaceutical cost for the out-patients. Indirect costs: we estimated the expense comparing our cases to literature data. Intangible costs: these are attributable to pain and psychological suffering. It is very difficult to express the intangible costs in monetary terms and they are often conveyed as disability and poorer quality-of-life. We used the Health Assessment Questionnaire "HAQ" and the Short Form-36 "SF-36" to evaluate this issues. RESULTS: Our study confirms, the extremely high costs caused by Systemic Sclerosis (total cost's 2001 year is 1,173,842.93 Euro, and average yearly patient cost is 11,073.99 Euro). Considering an estimated prevalence of 375 cases/106, the total yearly economic impact of SSc in Italy should be 249 million euro. Intangible costs were calculated as modifications of the health status. Average value of the HAQ was significantly higher than the control population (0.94 +/- 0.72), average values in the SF-36 were significantly lower than the control population (49.99 +/- 19.16 for physical dimension and 58.42 +/- 27.71 for mental dimension). The diffuse form of SSc, anti-Scl 70 antibodies, high skin score and a poor health status (HAQ and SF-36) were found to be cost predictors. CONCLUSIONS: As reported in the literature, our study confirms, the extremely high costs for total and single patients caused by Systemic Sclerosis. The DSSc are more expensive than the LSSc approximately 11% (p=0.0067). The direct costs are 30% higher in the DSSc than the LSSc (p < 0.001). The indirect and intangible costs are not significantly different. Moreover, our study shows also the possibility of identifying different cost predictors.

[Evaluation of quality of life in patients with systemic sclerosis by administering the SF-36 questionnaire]. / Valutazione della qualità della vita in pazienti affetti da sclerosi sistemica mediante somministrazione del questionario SF-36.

AIMS: To evaluate the quality of life of patients affected by systemic sclerosis (SSc) through the application of the Medical Outcome Survey Short-Form 36 (SF-36) questionnaire and to correlate the results with the disability index of the health assessment questionnaire (HAQ-DI) and the systemic involvement. METHODS: We studied 95 (3 M, 91 F) patients affected by SSc (mean age 60 years, range 39-83, mean duration of disease 6 years, range 1-34). The organ system involvement was evaluated by skin score, chest High Resolution Computed Tomography (HRCT), electrocardiography according to Holter, Doppler-echocardiography and esophagogram. RESULTS: Considering the values of the 8 question groups of the SF-36 the most different between the patients and the control population are the values relevant to the physical dimension. The general health values estimating the physical and social dimension are significantly lower in the patients than in the control population (t=9,324; p<0,0001). A very good correlation was found between the DI (r = -0,7903; p <0.0001) and all the scores of SF-36. The skin involvement showed a statistically significant correlation with the DI (r=0.3709; p=0.0002) and the PA score of the SF- 36 (r =0.2853; p=0.0051). No other statistically significant correlation was found between any of the SF-36 dimensions and involvement of a specific organ. CONCLUSION: SF-36 showed to be a valid instrument to evaluate the quality of life and the disability of patients with SSc and it seems to correlate with extent of skin involvement.

Dynamical relativistic effects in quasielastic 1p-shell proton knockout from 16O

We have measured the cross section for quasielastic 1p-shell proton knockout in the 16O(e,e(')p) reaction at omega = 0.439 GeV and Q2 = 0.8 (GeV/c)(2) for missing momentum P(miss)

[CRIB score: mortality, morbidity, and long-term neurologic development]. / CRIB score: mortalità, morbilità e sviluppo neurologico a distanza.

The purpose of this study is to assess the possibility of predicting mortality, major pathology and long-term neurodevelopmental impairment in very low birth weight VLBW infant using Clinical Risk Index for Babies (CRIB). We studied a cohort of 251 VLBW infants, whose CRIB could be calculated, born from 1995 to 1998 in our Unit. We analyzed the mortality before discharge, the incidence of chronic lung disease (CLD) and of retinopathy of prematurity (ROP), the length of stay before discharge and the neurodevelopmental impairment at one and two years of corrected age using the Griffiths developmental scales (impairment was defined by a general quotient of 85 or below). The CRIB score was divided into three risk groups: 0-5, 6-10 and > 10. Mortality rate raises with the CRIB's increase (respectively 5.6% in the first group, 32.4% in the second and 93.8% in the third group); besides the incidence of severe ROP and of CLD, calculated in infants survived > 28 days, is higher (18.4% and 40.7% respectively) in the second group than in the first (1.9% and 7.4% respectively). In the end, the incidence of neurodevelopment impairment at one and two years of corrected age is respectively 6.8% and 6.0% for children with CRIB 0-5 and 29.4% and 21.4% for children with CRIB 6-10. CRIB score is strongly associated with mortality and there is an increasing risk for severe ROP, CLD and neurodevelopment impairment from class 0-5 to class 6-10; no statement can be made for these diseases in class > 10 because there is only one survivor in this class.

[Early protected discharge of the mother and the neonate: case-control study]. / Dimissione precoce protetta della madre e del neonato: studio caso-controllo.

Aim of this study is to compare traditional post-partum hospital stay to hospitalization associated with early protected discharge: a case-control study has been performed to evaluate outcome as mother's appreciation of the experience as well as breastfeeding. The study included 50 healthy-term newborns and their mothers, discharged within 24 and 48 hours of life, and 44 controls, who had traditional "rooming-in" stay, delivered at the Department of Neonatology--University of Turin. The protocol included a midwife daily home visits and a neonatologist and nurse visit within 4th to 5th day of life, to evaluate mother's and baby's health status and to perform metabolic screenings. An ambulatorial follow-up visit at 1 month of life and 2 telephone interviews, at 3rd and 6th month, were also planned. During the first week of life 45 (90%) early discharged newborns had complete nursing (breastfeeding + water or other fluids), 4 (8%) had complementary nursing (breastfeeding + formula) and 1 (2%) received formula. Among controls, 46 (92%) babies received complete nursing, 2 had complementary nursing and 2 had artificial nursing. At 6 months of life breastfeeding was complete for 2% of cases and 6% of controls; in 44% of cases and 56% of controls nursing was complementary. Readmissions to our Birth Center were 2 among early discharged newborns, 1 in the control group. About project's appreciation, 96% of early discharged and 98% of control group mothers declared their availability to repeat the experience. Caring and supporting were judged adequate in 94% of both group. By adequate supporting of mother and newborn, short and traditional hospitalization are both pleasant and don't seem to present significant differences in type and length of nursing.

Neonatal drug addiction.

In the twenty years since the first case of neonatal drug addiction (resulting from the mother's use during pregnancy of morphine, heroin, methadone, cocaine) was referred to our attention, there has been a steady increase in the number of cases per year. Heroin alone or in association with methadone now represents the drug used by approximately 80% of addicted mothers. Over the past few years the mean age of mothers has increased; the number of drug users who do not appear to be addicts has also increased and a number of cases have lately been discovered only on the basis of neonatal symptoms, without any previous anamnestic indication. Neonatal abstinence syndrome (NAS) is the most striking effect of fetal exposure to drugs. Symptoms are easily recognised; pharmacological treatment can consist of either sedatives or replacement drugs whose dosage depends on the severity of withdrawal symptoms evaluated using a score system. NAS symptoms are usually resolved within a few days although some signs, especially irritability and tremors, may persist until 3 months of age. The main concern at present regards the future of these neonates. The most severe risk to which they are exposed, after HIV infection, is social; during the past few years in over 50% of cases parental authority has been suspended by the juvenile court. No long-term neurologic or cognitive deficits are directly associated with heroin or methadone use during pregnancy.

[Correlations between gastric erosions and duodenal ulcer. Endoscopic study]. / Correlazioni fra erosioni gastriche e ulcera duodenale. Studio endoscopico.

123 varioliform, 105 aphthous and 48 haemorrhagic flat erosions were noted in 2618 gastroduodenoscopies. A high incidence of erosions were associated with duodenal ulcer (43% of duodenal ulcers), especially in varioliform types and antrally. It is suggested that antral varioliform erosions form an integrating part or even the sole expression of an ulcer, and thus be seen as "sentinels" of an existing, potential or prior duodenal ulcer. Based on statistics, this view is supported by the maximum stimulus acidograms, which show that the PAO in antral varioliform erosions form an integrating part or even the sole expression of an ulcer, and thus be seen as "sentinels" of an existing, potential or prior duodenal ulcer. Based on statistics, this view is supported by the maximum stimulus acidograms, which show that the PAO in antral varioliform erosggested that antral varioliform erosions form an integrating part or even the sole expression of an ulcer, and thus be seen as "sentinels" of an existing, potential or prior duodenal ulcer. Based on statistics, this view is supported by the maximum stimulus acidograms, which show that the PAO in antral varioliform erosion without duodenal ulcer is within the range for duodenal patients. The employment of PAO is thus proposed in all cases of isolated antral varioliform gastric erosion, particularly in the absence of other possible causes.

Pharmacopoeia as quality codex for the manufacturers.

Three are the basic features of a medicine legally introduced on the market: efficacy, safety and quality. With regarding to drugs listed in a national or international pharmacopoeia, the ratio between efficacy and safety, within the range of dosage established by the codex, must be considered as official by the industry. As far as quality is concerned, the pharmacopoeia plays a fundamental role in establishing methods of analysis and technical control intended as official reference in case of controversy. The quality of drugs, pharmaceutical adjuvants or preparations listed in a modern pharmacopoeia must be considered by the industry as the minimum level of the acceptable standard for medical use, to ensure efficacy under proper storage conditions. In fact, the specifications are largely based upon suggestions made by manufacturers. Pharmaceutical specialties, being registered by Health Authorities following suitable documentation, do not have to be subjected to the standards established by the pharmacopoeia for new drugs or formulation adjuvants. The constant effort of the manufacturers to minimize risks leads to optimum quality levels, considering that samples used for control by the Health Authorities are usually picked from commercial packages containing a small number of units. To ensure statistical compliance of every sample with official pharmacopoeial standards, manufacturers are forced to exercise the highest care in every process of production and packaging. There cannot possibly be a guarantee that every single unit at the consumer's disposal will actually comply with the quality level established by a modern pharmacopoeia. Optimum quality level in every package of medical products can be achieved by following the "Good Manufacturing Practice" sponsored by the WHO; this goal requires skilled people and sophisticated equipment. The practice of quality control as an essential part of the manufacturing process in a wide range of pharmaceuticals, provides an excellent experience that may be useful to the pharmacopoeial commissions. Therefore a closer co-operation between health officials and industry's experts must be considered the best way to improve the specifications, to speed-up the revision of monographs and to collect reports on stability tests. The part of a modern pharmacopoeia, devoted to tests and standards appears today as the most important for the pharmaceutical industry because, when a controversy arises about drugs, the official methods established by the pharmacopoeia play a fundamental role in the enforcement of law. The task of compiling each new edition of a modern pharmacopoeia is becoming increasingly difficult; to speed revision any time a problem arises, the revision committees may seek advice from the numerous experts of the pharmaceutical industry thus achieving a most profitable collaboration.