Psychological outcomes of evening and night closed-loop insulin delivery under free living conditions in people with Type 1 diabetes: a 2-month randomized crossover trial.

AIM: To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system. METHODS: In a randomized crossover trial patient-related outcomes associated with an evening-and-night artificial pancreas and sensor-augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0-36, higher scores better) were completed by 32 participants. Semi-structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated-measures anova model or paired t-test when appropriate. RESULTS: The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor-augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were 'positive effects at work', 'improved blood glucose', 'fewer worries about blood glucose', but also 'frequent alarms', 'technological issues' and 'demand for an all-in-one device'. CONCLUSIONS: The psychological outcomes of artificial pancreas and sensor-augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems.

Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes.

AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.

Drug dose as mediator of treatment effect in antidepressant drug trials: the case of fluoxetine.

OBJECTIVE: This study aimed at investigating whether dose is a mediator of treatment effect in fluoxetine-randomized trials. Specifically, we investigated whether dose was higher in trials in which the aim was to demonstrate fluoxetine efficacy in comparison with older antidepressants and lower in trials in which the aim was to demonstrate a new drug's efficacy against fluoxetine. METHOD: We applied the model developed by Baron and Kenny to investigate the mediational role of drug dose on treatment effect. We included all randomized controlled trials comparing fluoxetine with other antidepressants as monotherapy in the acute-phase treatment of unipolar major depression. RESULTS: A total of 173 studies were included. In 76 comparisons (44%), fluoxetine was the experimental antidepressant. A metaregression analysis indicated that after adjusting for possible confounders, studies where fluoxetine was the experimental agent were associated with a significant advantage for fluoxetine. However, the Baron and Kenny model revealed no mediational role of drug dose in influencing treatment effect. CONCLUSION: The outcome of fluoxetine-randomized trials changed according to whether this drug was used as a new compound or as a reference. This finding cannot be attributed to antidepressants dose, as dose failed to emerge as mediator of treatment effect in the Baron and Kenny approach.

Psychopharmacological treatment in borderline personality disorder: A pilot observational study in a real-world setting.

Psychotherapy is the cornerstone of treatment for borderline personality disorder (BPD) while pharmacotherapy should be considered only as an adjunctive intervention. In clinical practice, however, most of BPD patients only receive medication. The aim of the study is to first describe pharmacological treatment in BPD patients in Italy and secondly to evaluate if comorbidity or illness severity are associated with the prescription of different class compounds. Data on pharmacological treatment and clinical evaluation of 75 BPD patients were collected in 5 clinical settings. The association between comorbidity and medication was assessed. Moreover, we evaluated the association between pharmacotherapy and severity, defined by a cluster analysis aimed at detecting different groups of patients. Most of the participants (82.7%) were characterized by polypharmacy, with a mean of 2.4 medications per person. Interestingly, the prescription didn't seem to depend on/be based on the severity of the disorder and was only partially determined by the presence of comorbidity. In conclusion, our findings are similar to what described in other clinical studies, supporting the idea that medication management for BPD is only partially coherent with international guidelines. This pilot study confirms the need for more rigorous studies to gain greater understanding of this topic and diminish the gap between guidelines and the real clinical world.

Parental evaluation of a telemonitoring service for children with Type 1 Diabetes.

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. The service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents' perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents' perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children's diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents' suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0-100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value = 0.0001). The analysis of free text comments highlighted an improvement in mood, and parents' commitment was also proved by their willingness to pay for the service (median = 200 euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family's own peace of mind.

Risk of perioperative seizures in patients undergoing craniotomy with intraoperative brain mapping.

BACKGROUND: The identification of risk factors associated with perioperative seizures would be of great benefit to the anesthesiologist in managing brain tumor patients undergoing craniotomy with intraoperative brain mapping. METHODS: A series of 316 supratentorial craniotomies for tumor resection, in which intraoperative brain mapping was used, were analyzed. From January 2005 to December 2010 the occurrence of intraoperative and immediate postoperative clinical seizures was prospectively recorded into a database. Demographic data, tumor characteristics, preoperative seizure control, intraoperative events and anesthetic management were evaluated as risk factors for intraoperative clinical seizures. Additionally, the association between intraoperative clinical seizures and immediate postoperative seizures was evaluated. In order to determine the best predictors of intraoperative and immediate postoperative clinical seizures, a multivariable analysis by logistic regression was performed. RESULTS: Younger age, location of the tumor in the frontal and parietal lobe, brain mapping conducted under general anesthesia and non physiologic values of arterial carbon dioxide (PaCO2) during brain mapping were independent positive risk factors for the development of intraoperative clinical seizures. Location of tumor in the frontal lobe, antiepileptic polytherapy, intraoperative seizures requiring pharmacologic treatment during brain mapping, and blood on postoperative CT scan were independent positive risk factors for the development of immediate postoperative seizures. CONCLUSION: Clinical seizures are common intraoperative and postoperative complications of supratentorial craniotomies with intraoperative brain mapping. The identification of those patients at higher risk of seizures may guide intraoperative and postoperative medical management.

Abnormalities in cortical gray matter density in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients' affective, cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC). METHODS: Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38 ± 11; females: 16, 61%). RESULTS: BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (P<0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing. CONCLUSIONS: BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data.

Streptococcal pharyngitis in Italian children: epidemiology and treatment with miocamycin.

A prospective multicentre study of Italian children with acute pharyngotonsillitis was carried out to determine the incidence of beta-haemolytic streptococcal infection and its epidemiological characteristics and to evaluate the effectiveness of a recently marketed macrolide, miocamycin. From February 1988 to March 1989, 865 children (aged 5 months to 14 years) were enrolled in 11 paediatric departments. Of these 31.9% had a positive throat culture for beta-haemolytic streptococci (26.6% group A streptococci, 5.3% group B, C, D or F). In 68.1% of the patients the throat culture did not yield any pathogen and the disease was considered to be probably viral. No epidemiological (age, season of occurrence, sex) or clinical characteristics (fever, pharyngeal hyperaemia, exudate etc.) could differentiate children with streptococcal pharyngotonsillitis from those with a probably viral one. Breese's score correctly identified only 19.1% of the cases with group A streptococcal infection. Miocamycin was given 50 mg/kg/day in 2 divided doses for 10 days in 225 children with streptococcal pharyngitis. The drug exhibited good clinical efficacy (resolution or improvement of acute signs and symptoms) in 96.3% of the children and a microbiological efficacy (eradication of the causative bacteria) in 85.3%.

Absorption of phenoxymethylpenicillin from mixtures and tablets in healthy volunteers.

The absorption of the potassium, calcium and benzathine salts of phenoxymethylpenicillin, given as mixtures, was investigated in twelve healthy volunteers. The potassium salt gave the fastest and highest serum peak levels. Also the relative bioavailability of the potassium salt was greatest, as indicated by the areas under the serum concentration/time curves (AUC). In a second study with twelve other volunteers, the absorption of the mixtures and tablets of the potassium salt was studied. The peak serum levels and AUC were comparable after these preparations. The results in our two studies indicate that, from a pharmacokinetic point of view, the potassium salt of phenoxymethylpenicillin in mixtures should be preferred in clinical practice. It also appears that the absorption of phenoxymethylpenicillin from the tablets and mixtures of the potassium salt is comparable, giving the same relative bioavailability.

[Cystic dysplasia of the testis: report of a case and review of the literature]. / Displasia cistica del testicolo: descrizione di un caso e revisione della letteratura.

Cystic dysplasia of the testis (CDT) is a rare, benign and congenital lesion causing scrotal mass in pediatric population that can mimic testicular cancer. This lesion consists of cystic dilation of the rete testis and it is frequently associated with renal or genitourinary tract anomalies as renal agenesis and multicystic dysplasia of the kidney. This frequent presentation suggests that testicular cystic dysplasia is associated with a defect of the metamesonephric system in particular with a defect in the connection between the efferent ducts derived from the mesonephros and the rete testis tubules derived from the gonadoblastoma. The role of ultrasound is of primary importance for clinical diagnosis and follow-up of untreated forms. The sonographic appearance of CDT consists of multiple cysts in the mediastinum testis. The cysts range in size from microscopic to several millimetres and may involve the whole testicular parenchyma or have a focal aspect. If the cysts are tiny, the ultrasound must be able to distinguish between CDT and testicular microlithiasis, a potential premalignant condition. Today it is possible thanks to high frequency 7.5 to 10 mHz probes. In the past orchiectomy has been considered as the treatment of the choice for CDT. Today, non operative management of CDT represents an effective alternative option in these patients and the primary benefit of this approach is the preservation of endocrine function and spermiogenic activity. However, the natural history of untreated CDT and its effect on normal testicular tissue are still unknown, therefore long-term follow-up is recommended.

[The beta-hemolytic Streptococcus group A carrier state]. / Stato di portatore di Streptococco beta emolitico gruppo A.

In this study we describe the group A streptococcal upper respiratory tract carrier state, following a clinical method based on two main elements: the presence or the absence of symptoms and the result of throat swab. Through this method we are able to decide how to face each individual clinical case.

[Evaluation of the compliance of thalassemic patients at a structured ambulatory day hospital]. / Valutazione della compliance in pazienti talassemici afferenti ad un ambulatorio D.H. strutturato.

The institution of a self-constructed Ambulatory where both pediatric and adult patient can be assisted with Day-Hospital, gains novelty and new characteristics when four different physicians (Medical, Pediatrician, Hematologist and Psychologist) structured part-time, contribute to functionality with equal participation. Compliance was investigated through a computerized way.

[Therapy of Helicobacter pylori infections in children]. / La terapia dell'infezione da Helicobacter pylori in età pediatrica.

We consider Helicobacter pylori treatment in children, giving some indications about the necessity of the treatment, the drugs to use, the duration and the results of therapy. We give importance to the choice of some specific drugs and to the follow-up.

[Polythelia as a sign of other congenital malformations: a clinical example]. / La politelia come spia di altre malformazioni congenite: un esempio clinico.

The authors describe the clinical history of a girl with severe chronic constipation due to anterior ectopic anus, associated with supernumerary nipples. The authors underline the importance of possible associations between supernumerary nipples and other congenital anomalies.

[Screening of cholesterol levels in middle school students at the Community of Lainate (Milan)]. / Studio osservazionale sui livelli di colesterolo in alunni frequentanti le Scuole medie del Comune di Lainate (Milano).

An example of good integration of territorial sanitary services with hospital services. An observational study that pointed out cholesterol disorders in a pre-adolescent population of a little city next to Milan.

[Longitudinal study of a group of 56 infants with a birth weight of less than 1500 gms: mortality and neurological sequelae in relation to progress in intensive care technics]. / Studio longitudinale di un gruppo di 56 bambini con peso alla nascita less than or equal to 1500 grammi: mortalità e sequele neurologiche in relazione ai progressi nelle tecniche di terapia intensiva.

56 very low-birth-weight (less than or equal to 1500 gm) infants were admitted in our Neonatal Intensive Care Unit between january 1978 and december 1981. Mortality of these infants in the first year of life decreased from 50% in 1978 to 32% in 1981. Our study confirms that mortality is significantly higher in transported infants. As to those born in our Hospital, mortality is markedly higher for breech delivery than for cephalic delivery or caesarian section. The amelioration of intensive care techniques, i.e. continuous transcutaneous PaO2 monitoring, orotracheal intubation at birth and improved respiratory care, markedly reduced the percentage of children with neuromotor pathology (from 43% in 1978 to 0% in 1981 in 16 survivors). Neurological follow-up was performed by serial controls until at least 2 years of age; Apgar scores and blood gas values are reported along with follow-up results to evaluate prognostic significance. Duration of orotracheal intubation, isolette requirement and feeding schedules are briefly discussed.

[Risk of bronchopulmonary dysplasia: the importance of diuresis]. / Rischio di displasia broncopolmonare: importanza della diuresi.

13 preterm infants (gestational age 34 weeks or below; birth weight under 1500 g.) with severe respiratory distress, were admitted for intensive care in our Unit between 1980 and 1981. Factors affecting the onset of BPD (bronchopulmonary dysplasia) in these subjects are evaluated by retrospective studies. Diuresis in the third day of life, expressed as a percentage of administered fluids appeared particularly significant. It resulted significantly lower in subjects developing BPD than in non-affected controls. Therefore, along with a PDA and a high fluid input favouring interstitial oedem, the inability of preterm infants to remove fluid overload must be considered. A reduced clearance of interstitial fluid in the lung enhances circulatory status and ventilatory damage and increases the risk of BPD.

[Cough and vomiting association in an infant: where does the vicious circle start?]. / Associazione tosse/vomito in un lattante: dove inizia il circolo vizioso?

The Authors describe the clinical history and diagnostical problems of a premature twin with the three classical symptoms cough-vomiting-growth retardation in the first year of life. Is the diagnostic route required to stabilize whether this condition is primarily gastroenterological or pulmonary?

[Multiple sclerosis and acute disseminated encephalomyelitis in children: a difficult diagnostic differentiation. Report of a young boy with early onset of the disease]. / Sclerosi multipla ed encefalomielite acuta disseminata: una diagnosi differenziale difficile. In merito ad un caso clinico con esordio molto precoce.

We report the case of an eight year old boy who developed suddenly acute left-sided hemiparesis syndrome. Brain magnetic resonance imaging (MRI) showed multiple white matter lesions. Therefore we considered in the differential diagnosis multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). The patient received intravenous immunoglobulin (IVIG), 1 g/kg/d over 2 days with complete regression of clinical symptoms. No relapses occurred within six months, although brain magnetic resonance imaging studies found new white matter lesions, suggesting multiple sclerosis with very early onset.

[Urokinase in a premature infant: its use in a case of right atrial thrombosis secondary to catheterization of the umbilical vein]. / Urochinasi nel prematuro: utilizzo in un caso di trombosi atrial destra secondaria a cateterizzazione della vena ombelicale.

Newborns with vascular catheters must be investigated by echocardiogram for intracardiac thrombosis. We report the use of urokinase to treat an asymptomatic right atrial thrombus in a 31 weeks' gestation newborn; the thrombosis occurred after placement of a catheter in the umbilical vein. We obtained a safe and successful thrombolysis using urokinase 4000 U/kg/h in continuous infusion.