Alessandro Dell'Erba

Unlicensed and off-label use of medicines at a neonatology clinic in Italy

ObjectiveMany drugs used for children are not licensed or are used off-label. An increased risk of medication errors and unexpected adverse drug reactions (ADR) associated with off-label and unlicensed drug prescription has been reported. This risk increases in the newborn, who are more likely to be predisposed to an ADR due to their physiological immaturity. The objective of this study was to describe the use of unlicensed or off-label drugs in a Neonatal Intensive Care Unit (NICU).MethodsAll drugs prescribed to newborn admitted to the Neonatology Unit of Bari University Hospital, from July 1st to August 31st in 2004 were recorded.Main outcome measuresAll the drugs prescribed were analysed with regard to their license status, then the licensed drugs were compared to the indications, dose, route of administration, duration of treatment, contraindications and warnings specified in the summary of product characteristics of the marketing authorization.ResultsData were collected on 176 prescriptions for 61 different drugs given to 34 newborns. Drugs were licensed in 88% and unlicensed in 12% of cases. About the licensed drugs, in 37.5% medicines were used following the terms of the marketing authorization, in 22.7% of cases medicines were used in an off-label manner as they contained no information for paediatric use in the marketing authorization and in 27.8% of cases medicines were licensed for paediatric use, but they were used off-label with regard to age, dose, route of administration and duration of treatment.ConclusionsDespite European and American initiatives aiming to promote greater awareness and research in the paediatric population, these data demonstrate that there is still a high percentage of unlicensed or off-label drugs use in neonatology, underlining the need to stimulate scientific data collection by means of experimental studies or outcome research.

Sudden cardiac death and myocardial ischemia indicators: a comparative study of four immunohistochemical markers.

The postmortem diagnosis of acute myocardial infarction represents a current challenge for forensic pathologists, particularly when death occurs within minutes to a few hours after the ischemic insult. Among the adult population the single most important cause of sudden cardiac death (SCD) is the well-known atherosclerotic coronary artery disease, commonly asymptomatic or unrecognized. The recognition of early myocardial damage using routine hematoxylin and eosin (H&E) staining is possible only if death has occurred at least 6 hours after the onset of the ischemic injury. The usefulness of immunohistochemical markers to the diagnosis of early myocardial damage has been recently suggested because most of them can be visible even serologically as early as few minutes after the beginning of the symptoms. To evaluate the usefulness of plasma and cellular antigens, their distribution patterns have been studied among a group of 18 SCD cases in which a myocardial ischemia was strongly suspected. For the present study, 4 markers have been selected on the basis of their different diagnostic potential as follows: among the plasma markers the C5b-9 and fibronectin, among the cellular markers the myoglobin and cardiac troponin. The results show that only the study of multiple markers such as those selected can provide enough evidence of myocardial ischemia and/or necrosis, supporting the final diagnosis of SCD. No single immunohistochemical staining is ideal for diagnosing early myocardial ischemia but a set of markers can improve the ability of forensic pathologists to detect ischemic areas when no macroscopic or microscopic evidence of necrosis is available. However, the interpretation of data obtained in each individual cannot be isolated from the overall assessment of the factors (cardiopulmonary resuscitation and/or agonal artifacts) that can affect the expression of each marker.

Off-label and unlicensed drug use among neonatal intensive care units in Southern Italy

Many drugs used for neonates are unlicensed or off‐label. An increased risk of medication errors and unexpected adverse drug reactions is associated with their use. This risk is even higher in preterm newborns, because of their physiological immaturity and the exposure to many different medicines. The objective of this study was to evaluate the use of unlicensed or off‐label drugs in eight tertiary‐level neonatal intensive care units (NICU) from two different southern Italian regions.

Craniofacial Identification by Comparison of Antemortem and Postmortem Radiographs Two Case Reports Dealing With Burnt Bodies

Two cases of positive identification of burnt bodies by radiographic comparison are reported. They emphasize that antemortem radiographs of the head are an important but sometimes overlooked source of information which can frequently provide useful objective data for comparison purposes. A positive identification can easily be achieved by medical examiners through visual comparison of the antemortem with the postmortem cranial and facial structures, even of bodies severely damaged by fire. In these bodies the radiographs of the skull can graphically depict structures which are often unique to the individual, such as the frontal sinus pattern and the morphology of dental restorations. However, the process of identification through radiographs is appropriate only in burnt bodies in which antemortem radiographs of the alleged deceased are available for comparison and unique craniofacial structures are still present on the body in a well-preserved state or at least not completely destroyed by fire, depending on the extent of the burn injury. Matching of corresponding features seems preferable to other methods of personal identification such as skull-photo superimposition, morphometric analysis, and/or other computer-aided methods since these techniques need trained personnel, as well as expensive equipment which is not invariably available in the medical examiners office or department of anthropology.

Laboratory request appropriateness in emergency: impact on hospital organization

Abstract Within the activities of the Risk Management Unit of the Bari Polyclinic Hospital Corporation, an anomalous trend was found, with excessive requests for urgent laboratory tests being made in the time period between 05:00 and 07:45h. In addition to slowing down laboratory operations, this anomaly suggested the possibility of inappropriate testing, at least in terms of the request mode, if not in absolute terms. An audit was implemented within the facility to check the grounds of this suspicion and to identify any errors and/or critical points. The results gathered are extremely interesting, as they show deficiencies at both the organizational and clinical level. The final objective of the investigation is to draft a common corporate procedure.

Undetected patricide: Inaccuracy of cause of death determination without an autopsy

Patricide (killing the father) is uncommon form of homicide. Usually the assaults occur at home in the absence of witnesses and adult sons are frequently involved. Homicides in a domestic context usually do not tend to recurrence, because the motivation for the crime ends with the death of the parent. However, this is not what was observed in the present case study dealing with the death of a 70 years old white man originally misclassified as accident and discovered three years later only after an additional homicide in a family context of a 60 years old white lady. Multiple stab wounds to the neck and thorax were misinterpreted at the external male body examination as blunt trauma falling down stairs. No forensic autopsy was requested and no comparison of medical findings with the results from the death scene, such as a bloodstain analysis was performed by the police officers nor required by the judicial authority. This was quite surprising because an additional but preliminary post-mortem external examination performed by a general practitioner on the male body already raised the suspicion that the external lesions were stab wounds thus requiring a forensic autopsy. Only the exhumation of the elderly body, performed years later, confirmed the diagnostic hypothesis raised by the first physician. The present case is quite representative of a death investigation not run professionally and performed by individuals with no specific training where most of the medico-legal investigations (especially for traumatic and violent deaths) are restricted to an external body examination without subsequent autopsy. Although misinterpretation of external lesions is inevitable and significant discrepancies between external body examination and forensic autopsy are not rare, in the case of contradictory results of post-mortem external examination or unclear/suspicious cause and manner of death, investigation should proceed necessarily with a forensic autopsy.

Unusual Death of a Transvestite: Identification of Crime Weapon and Survival Time*

Abstract:  The authors report a case of a transvestite found murdered near his automobile with several lacerated contused wounds to the face and cranial fractures. Autopsy revealed that the cause of death was a serious head trauma with subdural and subarachnoidal hemorrhages. In order to identify the crime weapon, a scanning electron microscopy (SEM) was used which revealed metallic residue on the skin fragments with the same molecular composition of the car paint. As for survival time, antibody anti‐beta‐amyloid precursor protein (APP) was applied to brain fragments and brainstem tissue, allowing for axonal varicosities (which form 2 to 3 h following death) to be observed under the optic microscope. So, by using SEM we understood that the fatal cranial‐encephalic lesions were the result of the victim’s head being repeatedly struck against the car door while anti‐betaAPP led to the understanding that the time elapsed between injury and death was less than 2 to 3 h.

Handover checklist: testing a standardization process in an Italian hospital

Objectives This study aimed to standardize and rationalize the handover, a critical and essential moment in common health care practices, through the realization of an efficient and standardized checklist, which could be used daily to ensure complete, thorough and effective handover. The principal purpose of the implementation of the handover is to reduce errors due to superficial and insufficient communication. Methods The “operative group” defined the phases to the realization of the delineated aims: at first, the direct observation and the consequent realization of a handover checklist model and then, the experimental phases (trials). The handover checklist model was used for a month and it was daily and duly completed by the doctors who took part in the trial. To prove the success of the study, three questionnaires were distributed on different occasions. Results Analyzing the answers to the questionnaires, the importance of the handover has come to light and that for the most part, the doctors consider it an essential and irreplaceable moment in daily health care work. Moreover, it became obvious that the use of the handover checklist guaranteed a considerable improvement in the traditional handover in terms of security, completeness, care continuity and clarity. The handover checklist was completely appreciated by the majority of the participant doctors who agree with the definitive introduction of it in their unit. Conclusions Our study indicated the consistency of the handover checklist as an instrument to implement the handover and, indirectly, to improve the quality of the care.