The Italian neuromuscular registry: a coordinated platform where patient organizations and clinicians collaborate for data collection and multiple usage.

BACKGROUND: The worldwide landscape of patient registries in the neuromuscular disease (NMD) field has significantly changed in the last 10 years, with the international TREAT-NMD network acting as strong driver. At the same time, the European Medicines Agency and the large federations of rare disease patient organizations (POs), such as EURORDIS, contributed to a great cultural change, by promoting a paradigm shift from product-registries to patient-centred registries. In Italy, several NMD POs and Fondazione Telethon undertook the development of a TREAT-NMD linked patient registry in 2009, with the referring clinical network providing input and support to this initiative through the years. This article describes the outcome of this joint effort and shares the experience gained. METHODS: The Italian NMD registry is based on an informatics technology platform, structured according to the most rigorous legal national and European requirements for management of patient sensitive data. A user-friendly web interface allows both direct patients and clinicians' participation. The platform's design permits expansion to incorporate new modules and new registries, and is suitable of interoperability with other international efforts. RESULTS: When the Italian NMD Registry was initiated, an ad hoc legal entity (NMD Registry Association) was devised to manage registries' data. Currently, several disease-specific databases are hosted on the platform. They collect molecular and clinical details of individuals affected by Duchenne or Becker muscular dystrophy, Charcot-Marie-Tooth disease, transthyretin type-familial amyloidotic polyneuropathy, muscle glycogen storage disorders, spinal and bulbar muscular atrophy, and spinal muscular atrophy. These disease-specific registries are at different stage of development, and the NMD Registry itself has gone through several implementation steps to fulfil different technical and governance needs. The new governance model is based on the agreement between the NMD Registry Association and the professional societies representing the Italian NMD clinical network. Overall, up to now the NMD registry has collected data on more than 2000 individuals living with a NMD condition. CONCLUSIONS: The Italian NMD Registry is a flexible platform that manages several condition-specific databases and is suitable to upgrade. All stakeholders participate in its management, with clear roles and responsibilities. This governance model has been key to its success. In fact, it favored patient empowerment and their direct participation in research, while also engaging the expert clinicians of the Italian network in the collection of accurate clinical data according to the best clinical practices.

A Social Media-Based Acute Alcohol Consumption Behavior (NekNomination): Case Series in Italian Emergency Departments.

BACKGROUND: NekNomination, also known as NekNominate, Neck and Nominate, or Neck Nomination, is a social network-based drinking game which is thought to have originated in Australia and spread all over the world between 2013 and 2014. Individuals record videos of themselves while rapidly drinking excessive quantities of alcoholic drinks (necking) and then nominate friends to outdo them within 24 hours; the videos are then posted on social media such as Facebook or YouTube. The consequences of this drinking game have been very dangerous; at least 5 people under age 30 years have died after drinking deadly cocktails, and many others have suffered from alcohol intoxication. OBJECTIVE: The goal of the research is to evaluate data about clinically important acute alcohol intoxication among teenagers and young adults and inform and educate the general public, especially parents, teachers, and health workers, about the spreading craze of dangerous Internet-related behavior among today's teenagers and young people up to the age of 23 years. METHODS: Patients aged 15 to 23 years with acute alcohol intoxication who came to the emergency department (ED) of 2 major hospitals in Italy from January 1, 2011, to June 30, 2014, were included in this study. Data were retrieved from prehospital and intrahospital medical records and included personal information, methods of intoxication, triage color code, date and time of access to the ED, any relevant signs and symptoms, blood alcohol concentration, and diagnosis at discharge. RESULTS: A total of 450 young patients (male 277/450, 61.5%, female 173/450, 38.5%; age 15 to 16 years 15/450, 3.3%, age 17 to 18 years 184/450, 40.9%, age 19 to 23 years 251/450, 55.8%) were recruited. The causes of intoxication were happy hour, binge drinking, NekNominate, eyeballing, other alcoholic games, or a mix of them. Happy hour was found to be more common among the older patients, whereas NekNominate accounted for almost half of the youngest group of hospitalizations. Eyeballing occurred in 1.6% (7/450) of cases; binge drinking and other alcoholic games caused 23.3% (105/450) and 23.8% (107/450) of hospitalizations, respectively. On admission, 44.2% (199/450) of patients were assigned a red or yellow color code requiring immediate medical attention; about 14% of them required additional medical assistance (after being in the ED) or hospitalization, some in semi-intensive care units. CONCLUSIONS: Our study shows that the increased numbers of hospitalizations due to alcohol intoxication in the adolescent age group, as a consequence of NekNominate or other drinking games, is alarming and represents a serious public health issue. The potential markers of improper use of social networks must be clearly identified, including categories at risk of alcohol abuse, in order to develop intervention and prevention strategies in terms of education and awareness, which may help in averting potentially fatal episodes.

Mirtazapine fatal poisoning.

Mirtazapine is a noradrenergic and specific serotoninergic antidepressant agent that stimulates norepinephrine and serotonin release while also blocking serotonin receptors (5-HT2 and 5-HT3). Although the drug is used extensively, at present we do not know of any fatal cases due to mirtazapine alone. On the contrary, the published literature describes several fatal poisoning cases related to the intake of mirtazapine together with other drugs. Here we describe a fatal case of mirtazapine self-poisoning, since the other drug detected (lorazepam), was within the therapeutic range. Analyses were performed by LC-MS/MS on body fluids and a hair sample and mirtazapine concentration measured in blood was very high: 9.3mg/L. N-Desmethylmirtazapine was also quantitated. We then compared our results with those of previously published cases. In conclusion, even though mirtazapine can be considered a relatively safe drug, taking a large amount alone or in combination with other drugs, could lead to death.

Planking or the "Lying-Down Game:" Two Case Reports.

BACKGROUND: The monitoring and management of risks regarding children and young people admitted to the emergency department as a result of dangerous behaviors distributed via the Internet should be based on clinical reasoning and knowledge about these social media-related phenomena. Here we examine 2 cases of teenagers who reported severe injuries while performing the "planking" craze, a challenge that consists in lying face-down stiffly like a board on any kind of surface. OBJECTIVE: Our objective is to examine and describe the Internet craze called planking, also known as the "lying-down game," through 2 case reports from our experience, enriching this study with information gained through discussions with secondary school teenagers. METHODS: Details of the 2 case reports were taken from electronic medical records giving information on care support processes, care management, and the costs of traumatic episodes. Demographic data, hemoglobin and serum lactate values, and Injury Severity Scores were evaluated. The study took place in secondary schools of our city from 2013 to 2014 during medical education courses, with the aim of analyzing the influence of social media on teenagers' activities and behaviors. RESULTS: Both patients suffered multiple trauma injuries and needed high-level health assistance. The first patient underwent a splenectomy and the second one a nephrectomy; both of them required a long hospital stay (14 and 20 days, respectively), and the costs for their management have been estimated at US $27,000 and US $37,000, respectively. Their decision to perform the planking in dangerous locations was due to their ambition to gain peers' acclaim through shared videos and pictures. CONCLUSIONS: Reporting and understanding these cases may potentially help prevent future events occurring in similar circumstances: the scientific community cannot leave this problem unaddressed. There is also a role of education resources for health care professionals; for this, we must identify and follow up strange or misleading information found on websites. A key element of this research study was to report physicians' misperceptions concerning planking and, with these cases used for teaching purposes, improve knowledge of the clinical and forensic aspects of this emerging problem.

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study.

OBJECTIVES: Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. METHODS: 133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups. RESULTS: In the whole OAT group both warfarin and 3'-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3'-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3'-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3'-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3'-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles. CONCLUSION: Our results overall suggest that 3'-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.

The perils of dental vacation: possible anaesthetic and medicolegal consequences.

INTRODUCTION: The aim of this paper is to emphasize anaesthesiologists' difficulty in detecting poor dentition in cases of poorly applied prostheses and/or advanced periodontal disease, and to establish whether it is possible, and in which conditions, to calculate compensation in cases of dental damage postlaryngoscopy and/or intubation. The main complex problem here lies in trying to reconstruct exactly what the dental situation was before the teeth were damaged. For this reason the important preoperative factors (dental prostheses, crown fractures, parodontal disease, etc.) must be clearly shown before surgery on a dental chart. CLINICAL CASES: Two cases of interest, both to anaesthesiologists practising intubation and medicolegal physicians who have to deal with potential claims, are briefly reported. The first patient was a 55-year-old diabetic patient, who underwent emergency surgery for acute abdominal pathology. He had gone outside Italy for dental treatment three years previously and now presented with very poor pre-existing dentition, carefully noted on an anaesthetic chart. He now demanded compensation for dental damage due to intubation in Italy; the resulting dental treatment was very expensive because substantial remedial work was required. The second patient had received treatment outside Italy, work which involved cosmetic coating of the teeth. After surgery in Italy, she demanded compensation because one tooth, which had been coated and appeared to be healthy, was broken after emergency intubation. In both cases, the patients demanded very high compensation. COMMENT: Dental tourism alone accounts for more than 250,000 patients each year who combine a holiday with dental treatment in Eastern Europe. However, if prosthetic devices or conservative treatments are not applied correctly, it should be noted that durability may be poorer than expected, but iatrogenic damage may also be caused.

A fatal case of anaphylactic shock during paragliding.

The growth in popularity of flying ultralight aircraft and paragliding has been associated with an increased involvement of Emergency Medical Services because of various types of trauma suffered from both inexperienced and skilled individuals. This case presentation reports on a paraglider pilot, who was seen spinning "unusually" rapidly toward the ground, without visible attempts to regain control of the aircraft. Besides the bilateral mydriasis and the absence of any ECG activity, there was a significant swelling of face, lips, neck, and tongue. Upon opening the mouth, a dead bee was found over the tongue, underneath the palate. A fatal anaphylactic shock was the likely cause of death of the pilot while still "in mid-air." This case is certainly different from the commonly reported accidents during paragliding. An updated review of the medical literature shows no reported cases of fatal anaphylactic shock during the practice of paragliding.

Traumatic dental injuries during anaesthesia. Part II: medico-legal evaluation and liability.

INTRODUCTION: Claims for tooth damage following intubation are increasing. An anaesthetic chart (AC) has been proposed to describe patient's pre-existent dental diseases and any possible lesions caused during intubation and extubation. MATERIALS AND METHODS: We conducted a retrospective study of 235 cases of dental lesions reported in litigation files from January 2000 to June 2009. Based on preoperative oral inspection the anaesthetist decided whether or not to use a protective aid. Two different tooth protectors were applied: (i) a standard mouthguard and (ii) silicone impression putty. RESULTS: The study population consisted of 110 female (age 6-88 years) and 125 male patients (11-90 years) patients. In 66% of cases greater risk of perianesthetic dental injury was reported in the AC due to pre-existing poor dentition. In intubation procedures without protective devices dental subluxation/luxation occurred in 55% of patients, dental avulsion in 43%, exfoliation in 2%, and soft tissue damage in five patients. One patient suffered from transient facial nerve paralysis. The costs of treatments and of impression materials, as well as the total value of compensation for injuries are reported. DISCUSSION: Definition and demonstrability of damages on the AC is important in order to separate the cases worthy of compensation from the non-compensable ones, as to evaluate the possibility of solving the litigation by extrajudicial channels. There are cases in which, based on AC reporting and device adoption the damage resulted to be compensable, but the costs were defined on different estimates of lesions. The use of a protective device makes it possible to down-modulate the damage compensation. CONCLUSION: The analysis of litigation records and 'incident reports' has suggested that the choice of accurate proceeding and the use of protection aids could reduce the number of claims, insurance premiums and the costs of litigation process, thus improving physician-patient relationship.

Unusual Displacement of a Mobilised Dental Bridge during Orotracheal Intubation.

Dental trauma during tracheal intubation mostly happens in case of poor dentition, restricted mouth opening, and/or difficult laryngoscopy. 57-year-old man undergoing laparoscopic radiofrequency ablation of unresectable hepatocellular carcinoma had his dental work detached at induction of anesthesia. Oropharyngeal direct view, manual inspection, fibreoptic nosendoscopy, tracheobronchoscopy, and fiberoptic inspection of the esophagus and stomach were unsuccessful in locating the dislodged bridge. While other possible exams were considered, such as lateral and AP x-ray of head and neck, further meticulous manual "sweepings" of the mouth were performed, and by moving the first and second fingers below the soft palate deep towards the posterolateral wall of the pharynx, feeling consistent with a dental prosthesis was detected in the right pharyngeal recess. Only after pulling the palatopharyngeal arch upward was it possible to grasp it and extract it out with the aid of a Magill Catheter Forceps. Even though the preexisting root and bridge deficits were well reported by the consultant dentist, the patient was fully reimbursed. The lack of appropriate documentation of the advanced periodontal disease in the anesthesia records, no mention of potential risks on anesthesia consent, and insufficient protective measures during airway instrumentation reinforced the reimbursement claim.

Traumatic dental injuries during anaesthesia: part I: clinical evaluation.

UNLABELLED: Dental injuries represent the most common claims against the anaesthesiologist. Dental lesions are frequent complications of oro-tracheal intubation and major causal factors are (i) poor dentition, (ii) aggressive laryngoscopy, (iii) insufficient anaesthesia and curarization, (iv) emergency interventions and (v) lack of experience by the anaesthesiologist. MATERIALS AND METHODS: We conducted a retrospective analysis of 83 cases of dental lesions occurring during elective, emergent and urgent surgery requiring general anaesthesia with tracheal tube placement in the years between 2000 and 2008. Preoperative evaluation of dental status was obtained from the anaesthesiology chart, filled by an experienced anaesthesiologist during the preoperative visit. Anaesthesiological records were inspected by physicians of Legal Medicine Department with the aim to attribute responsibility for the damage and manage potential reimbursements. Costs related to the required dental repair were also noted. RESULTS: Eighty-three patients of a total of 60.000 surgical procedures (no day surgery) under general anaesthesia were affected by dental lesions (0.13%). Seventy-five per cent of lesions occurred during intubation manoeuvres for elective major surgery, 15% occurred at tracheal intubation for minor surgery and 10% were related to emergency surgery. Teeth avulsions accounted for 50% of lesions, followed by damage to crowns and bridges (14%), luxations and fractures (>15%). DISCUSSION: The overall incidence of dental injury in our retrospective study was 1.38 per 1000 anaesthetics, which is slightly higher than those reported by some and lower with respect to others. Avulsion of a permanent tooth occurred in patients who were affected by severe mobility of native teeth while undergoing surgery. Even though the majority of anaesthesiologists were trained enough in the use of airway devices and aware of the potential damage while using excessive forces, some unexpected difficulties may have led to lesions. It is known that damage to teeth can occur even in the absence of negligence.