Impact of rosiglitazone safety alerts on oral antidiabetic sales trends: a countrywide study in Portugal

Pharmacovigilance systems are important to monitor the safety of on‐market drugs after approval. The aim of this study was to assess the impact of rosiglitazone safety alerts on trends in the sale of rosiglitazone and other oral antidiabetic drugs. An ecological study was conducted, using temporally aggregated data and linking safety alerts to countrywide sales of all oral antidiabetic drugs in Portugal from January 2002 to December 2012. Sales figures for oral antidiabetic drugs marketed in Portugal were supplied by IMS Health Portugal with a breakdown by active substance and fixed combinations. The number of defined daily doses per 1000 inhabitants per day (DIDs) of each oral antidiabetic drug sold to the estimated diabetic population using oral antidiabetic drugs in Portugal was calculated. Particular attention was paid to the case of rosiglitazone, with the results being adjusted for changes in rosiglitazone reimbursement policies. A total of four safety alerts were issued about rosiglitazone. Rosiglitazone sales registered an increase of 32.9% (0.202 DIDs; P < 0.001) after the first alert (risk of macular oedema or worsening of pre‐existent macular oedema) in January 2006. After subsequent alerts about cardiovascular risks, this trend was not, however, repeated and sales fell. Following the January 2006 and January 2008 safety alerts, rosiglitazone sales described a long‐term downward trend, with decreases of 3.75% (?0023 DIDs; P > 0.05) and 0.24% (?0.001 DIDs; P > 0.05), respectively. It is important to promote the dissemination and publication of drug safety alerts.     

Impact of sibling death on children's behavior

Abstract

Research has indicated that siblings of deceased children demonstrate a variety of behavioral problems as a result of the death. The purpose of this study was to determine the relationship of selected factors and children's behavior during the first year following the siblings' deaths.

The sample included 33 boys and 32 girls ages 4 to 16 years who were the siblings of deceased children. Data on their behavior was obtained by an interview with the mothers using a standardized tool, the Child Behavior Checklist. Results showed that the bereaved children displayed significantly more behavior problems in comparison to standardized norms. The variables of age, place of death, family size, ill child's diagnosis, sex and age of deceased child, and funeral attendance were related to behavior problems in the surviving children.     

Suicide by non-pharmaceutical poisons in San Diego County

Background. In 2010, 6,599 poisoning suicides were reported in the United States (US). While medications remain the primary substances involved in completed poisoning suicides, successful fatal poisonings with non-pharmaceutical substances occur with some regularity. The goal of this study was to identify successful suicides caused by non-pharmaceutical self-poisoning in a large US county over the last 12 years. Methods. A large US-county medical-examiner's database was queried for all suicides in which exposure to non-pharmaceuticals was listed as the cause of death from 2000 to 2012. Substances were categorized by specific toxin when available and by product type when unavailable. Decedent age, sex, and circumstances surrounding each case were also reviewed. Results. Ages ranged from 18 to 95 (median 48) years. There were 159 (77%) males and 48 females. A total of 11 poisons were utilized. Discussion. Worldwide, intentional CO inhalation is a common method for committing suicide and intentional CO inhalation was the most common method of non-pharmaceutical self-poisoning suicide in our data. Other relatively common poisons including ethylene glycol and cyanide were employed in a relatively constant manner over time as well. Surprisingly, there have been an increasing number of helium-inhalation deaths in recent years. Conclusion. Inhaled toxins are the most popular (81%) in non-pharmaceutical suicides, likely due to their rapidity of death. Although much less frequently, individuals successfully employ a broad spectrum of other toxins to commit suicide.     

Methadone-related Deaths in Montpellier and Region,from 2000 to 2010

Purpose. The objectives of this analysis were to assess the role of methadone and related substances in death occuring, discussing methadone blood concentrations and the contribution of the autopsy to the accountability of methadone in the death process. Method. We retrospectively analyzed all forensic cases positive for methadone from January 2000 to December 2010, in Montpellier and the region served by our laboratory. Results. During the study period, 64 cases of deaths (11 women, 53 men) with methadone detection were recorded. A progressive increase between 2001 (2 cases) and 2010 (8 cases) was observed. The median age was 33 years old. An autopsy was available in 56.3% of cases. The most frequent finding at the autopsy was non-specific asphyxia death signs (67.6%). Tolerance to opioids was documented in 21 cases. The methadone blood concentrations ranged from 1 to 2 800 ng/mL (59 cases, median value 330 ng/mL). Most of the cases (88%) were polydrug intoxications. The most commonly associated drugs were benzodiazepines (61%), cannabinoids (28%), opioids (19%) and cocaine (12.5%). Conclusion. During a 11-year period, toxicological analyses related to 1991 death cases were performed at the Toxicology Laboratory of Montpellier University Hospital. Of these patients, 64 deaths were possibly related to methadone. Several relevant elements (biological analysis and autopsy) were used to attribute the deaths to the sole methadone (12 cases) or to methadone and associated substances (8 cases).     

Recreational drug use at a major music festival: trend analysis of anonymised pooled urine

Objective: The spread of new psychoactive substances (NPS) has expanded rapidly in the last decade. The complexity of the pharmacological effects of NPS challenges the traditional treatment guidelines, and information of the emergence of new arrivals is valuable. Our knowledge on the actual range of recreational drugs used and NPS available in Denmark is limited as identification is possible only when consumers become patients in the healthcare system or through drug seizures. We aimed to detect classical recreational drugs and NPS in the urine of music festival attendees and evaluate if the use of NPS could have been predicted by comparing study data with drug seizure data from the previous year published by European and Danish health authorities.

Methods: In a cross-sectional study, 44 urine samples were collected from three urinals at Roskilde Festival 2016—the largest Danish music festival. Two urinals were placed at music stages with late-night concerts, and one urinal was placed at a camp site. Samples were prepared using enzymatic hydrolysis followed by cationic and anionic solid phase extraction, and analysed using ultra performance liquid chromatography-high-resolution time-of-flight mass spectrometry (UPLC-HR-TOF-MS). Data were processed using an in-house library of 467 target substances, including legal and illegal drugs and metabolites. Urine drug-screening immunoassays were also evaluated and results were compared to UPLC-HR-TOF-MS results.

Results: In total, 77 drugs, including metabolites, were qualitatively identified in the 44 urine samples. The recreational drugs identified were amphetamine (n?=?30), cocaine (n?=?44), MDA (n?=?40), MDMA (n?=?44), THC-COOH (n?=?19) and ketamine (n?=?17). No NPS were identified. Sample testing using the urine drug-screening immunoassays showed presence of cocaine (n?=?27), methamphetamine/MDMA (n?=?4), THC (n?=?7), “Spice” (n?=?7) and methylphenidate (n?=?1). These discrepancies might be caused by differences in cut-off values between the analytical methods, limited specificity or cross-reactivity of the urine drug-screening immunoassays compared to UPLC-HR-TOFMS results.

Conclusion: Widespread uses of classical recreational drugs were identified in pooled urine samples. The prevalence of NPS was not as comprehensive as expected based on the European and Danish health authorities reports on illegal drugs. Urine drug-screening immunoassays results are advised to be confirmed by chromatographic bioanalysis.     

Medical management of deliberate drug overdose: A neglected area for suicide prevention?

Objectives: Overdoses account for a quarter of all suicides in England. The number of people who survive the immediate effects of their overdose long enough to reach medical attention, but who subsequently die in hospital is unknown. The aim of this study was to determine the proportion of overdose suicides dying in hospital and describe their sociodemographic characteristics.

Method: Cross sectional analysis of routinely collected Hospital Episode Statistics data for England (1997 to 1999) to identify hospital admissions for overdose among people aged 12+ and the outcome of these admissions.

Results: Between 1997 and 1999 there were 233 756 hospital admissions for overdose, 1149 (0.5%) of these ended in the death of the patient such deaths accounted for 29% of all overdose suicides and 7% of total suicides. The median time between admission and death was three days (interquartile range one to nine days). The most commonly identified drugs taken in fatal overdose were paracetamol compounds, benzodiazepines, and tricyclic/tetracyclic antidepressants.

Conclusion: Around a quarter of all overdose suicide deaths occur subsequent to hospital admission. Further more detailed research is required to discover if better pre-admission and inhospital medical management of those taking serious overdoses may prevent some of these deaths.

     

The use of palliative care services associated with better dying circumstances. Results from an epidemiological population-based study in the brussels metropolitan region

Context

There is some consensus that a “good death” is one which occurs at home, in the presence of loved ones, and is free of distress. Involvement of palliative care services is assumed to improve these circumstances.

Objectives

This population-based study describes characteristics of the end of life of patients dying in Brussels and examines their associations with the involvement of palliative care services.

Methods

In 2007, an anonymous large-scale mortality follow-back survey was conducted in Brussels by mailing questionnaires regarding end-of-life care and characteristics to the attending physicians of a representative sample of 1961 deaths.

Results

Response rate was 41% (n = 701). Of all deaths, 59% were nonsudden. Of these, 12% took place at home. For 27%, the attending physician was informed about the patient’s preferred place of death. When the preference to die at home was known, 66% died at home. At the moment of death, in 47% of nonsudden deaths, loved ones were present. In a quarter of deaths, palliative care services were involved. Involvement with palliative care services was more likely for cancer patients than noncancer patients and was associated with the attending physicians more often being informed about the preferred place of death, with patients more often dying at home, with loved ones more often being present, and with a better feeling of well-being on the last day.

Conclusion

Overall, circumstances at the very end of life are suboptimal in Brussels. This study provides a case for stronger involvement of palliative care as a focal point for policies to improve end-of-life circumstances in a metropolitan area such as Brussels.     

How do cancer patients receiving palliative care at home die? A descriptive study

Context

Data regarding the circumstances of the process of death of terminally ill patients followed at home are lacking.

Objectives

The aim of this study was to describe the characteristics and assess the circumstances of the process of death of terminally ill patients followed at home.

Methods

This was a prospective survey to assess the dying process of advanced cancer patients followed at home. Within a week after death, the principal caregiver was interviewed. Information from the palliative home care team and the caregiver about expectation of death, time of death, professional and nonprofessional people present at time of death, emergency admission to hospital, and administration of drugs to resuscitate was gathered. The principal clinical issues in the last two hours also were recorded.

Results

In total, 181 of 222 caregivers provided information. Most deaths were expected. Palliative home care team physicians and nurses visited the patient on the day of death but were occasionally present at the moment of death. More than three people were generally present at time of death. More than two-thirds of patients died peacefully, without apparent suffering, and 35.7% of them received palliative sedation before dying. In the last two hours, the most frequent clinical issues were ranked as death rattle, dyspnea, and agitation. In 10 cases, emergency drugs for resuscitation were administered.

Conclusion

This study has shown how advanced cancer patients die at home and that palliative home care may be helpful in allowing a death at home, particularly when relatives are actively involved.     

The impact of drug-related death on staff who have experienced it as part of their caseload: An exploratory study

Background: Previous research into drug-related death (DRD) has targeted specific groups such as the deceased themselves, witnesses, or families of victims. There has been no research on staff working in the substance misuse field and the impact that DRD has had on them.

Method: A postal questionnaire survey was conducted across a Scottish health authority area and quantitatively measured the impact that this event had on the work, health, and social life.

Results: Sixty-five staff persons were identified as having experiencing at least one DRD on their caseload. These 65 reported a range of grief-related reactions, with the majority (88%) identifying at least one reaction. The most common feelings identified were sadness (83%), guilt (40%), and anger (37%) about the death of their client. Female staff, those with access to more sources of support, those who had a larger caseload, those with greater career experience of DRD on their caseload, and those who felt close to their client all reported significantly greater prevalence of grief-related reactions. The length of time since the DRD had occurred was also associated.

Conclusions: When a DRD occurs, staff involved in the care and treatment of the deceased need to be considered in the aftermath.     

Most head injury related motorcycle crash deaths are related to poor riding practices

Objective: To report the characteristics of head injury related motorcycle crash deaths. Methods: Motorcycle crash deaths with head injury (Abbreviated Injury Severity score ≥ 2) between 1 January 1998 and 31 December 1999 were identified from the Western Australia State Coronial Database. Demographics, incident and death locations, type of incident and role of unsafe riding behaviour were examined. Results: There were 39 deaths analysed (35 motorcycle riders and four pillion passengers). The median age was 29 years (range 9–64 years), with 22 deaths (56.4%) in the range 15–29 years and 92.3% of those killed being male. Twenty‐one motorcycle crashes were single‐vehicle crashes (53.8%). There were 25 deaths at scene (64.1%). Ethanol was implicated in 12 cases (30.8%) and other drugs were implicated in 11 cases (28.2%). Speeding was implicated in 12 cases (30.8%) and a lack of appropriate safety equipment was implicated in five cases (12.8%). One or more of the unsafe practices above was identified in 23 cases (59%). Overall, there was no difference in the rate of unsafe practices in single‐vehicle incidents compared with incidents involving another vehicle (P = 0.342). Ethanol was associated with 10 single motorcycle incidents (47.6%) compared with two (11.1%) involving another vehicle (P = 0.018). Unsafe practices were involved in 76% of at‐scene deaths, compared with 28.6% in those surviving to hospital (P = 0.007). Conclusion: A large proportion of head injury related motorcycle crash deaths are related to the unsafe behaviour of motorcyclists. A preventative campaign focusing on young male motorcycle riders and unsafe driving behaviour may reduce this death toll.     

Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations

BackgroundPoisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication.MethodsBlood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x²) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05).ResultsOf the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 μg/mL ± 0.45 and 0.38 μg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic.ConclusionThe application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.     

Personal communications

Abstract

We conducted 14 interviews representing 9 families and 10 child deaths to examine a dilemma common to bereaved parents-the definition of the family after the death of a child. Although the deceased child continued to be defined as a member of the family to the parents, the degree to which this definition of the family was presented to outsiders varied. The work of Boss (psychological presence/physical absence and boundary ambiguity) and Goffman front-stage performance / backstage reality) facilitates an understanding of this dilemma. Implications for grief counseling are discussed.     

Holding a Place: Parents' Lives Following Removal of Infant Life Support

There are 34 000 neonatal deaths occurring annually in the United States, many of which occur after removal of life support. The purposes of this grounded theory study were to explore and describe parents' experiences with making the decision to discontinue life support for their critically ill infant and to identify the process that allows them to then move forward with their lives after the infant's death. Data were generated by face-to-face and telephone interviews with a theoretical sample of 15 parents. Three thematic concepts with subthemes emerged: Facing the Decision (No Real Choice, Time with the Infant), Life Goes On (Listen to Your Heart, An Abiding Loss, Not Left Out), and Lives Forever Changed (New Perspectives, Preparing to Meet Again). The substantive theory, The Process of Holding a Place, describes the basic social process parents used to carry their deceased infant forward with them in their daily lives.     

Testing Positive for Methadone and Either a Tricyclic Antidepressant or a Benzodiazepine Is Associated with an Accidental Overdose Death: Analysis of Medical Examiner Data

Objectives: Patients in emergency departments who use methadone frequently use tricyclic antidepressants (TCAs) and/or benzodiazepines (BZDs). This is a potentially dangerous drug combination. The authors hypothesized that the presence of methadone and a TCA, a BZD, or both is associated with an “accidental” overdose (AOD) death more often than a death from any other cause. Methods: A retrospective chart review of New York City Office of Chief Medical Examiner data for 2003 was performed. Decedents who tested positive for methadone that were classified as an AOD death, as determined by the medical examiner, were compared with deaths from all other causes for the presence of a TCA, a BZD, or both. A logistical regression was performed to develop a multivariate model identifying additional variables associated with a methadone‐positive AOD death. A p‐value of <0.05 was considered significant, and 95% confidence intervals (CIs) were calculated. Results: In 2003, there were 5,817 medical examiner cases, of which 500 (8.6%) were methadone positive. Of the methadone‐positive cases, 493 were available for analysis; 95 (19.3%) were TCA positive and 158 (32.0%) were BZD positive. The odds of having an AOD death in methadone‐positive decedents testing TCA positive, BZD positive, or both were 2.11 (95% CI = 1.32 to 3.37; p < 0.01) for TCAs, 1.66 (95% CI = 1.12 to 2.45; p < 0.02) for BZDs, and 4.34 (95% CI = 1.97 to 9.56; p < 0.001) for both. The multivariate logistic regression of analytes revealed the following covariates associated with an AOD death as well: amitriptyline, cocaine, morphine, or opiates. Conclusions: Among the methadone‐positive cases, testing positive for a TCA, a BZD, or both was associated with an AOD death.     

Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review

ObjectiveBenzodiazepines are often recommended first-line for management of cocaine and amphetamine toxicity while antipsychotic treatment is discouraged due to the potential for lowering seizure threshold, prolonging the QT interval, and decreasing heat dissipation. We performed a systematic review including animal and human studies to elucidate the efficacy and safety of antipsychotics in managing sympathomimetic toxicity specifically evaluating the effect of treatment on mortality, seizures, hyperthermia, and cardiovascular effects.MethodsWe searched MEDLINE, Embase, BIOSIS Previews, Web of Science, Scopus, CENTRAL and gray literature from inception to 31 May 2017 to answer: Can antipsychotics be used safely and effectively to treat cocaine or amphetamine toxicity? Citations were screened by title and abstract. Additional citations were identified with citation tracking. Data were extracted from full-texts.Results6539 citations were identified; 250 full-text articles were assessed. Citation tracking identified 2336 citations; 155 full texts were reviewed. Seventy-three papers were included in this review. In 96 subjects with cocaine toxicity treated with an antipsychotic, there were three deaths, two cardiac arrests, two seizures, and one episode of hyperthermia. In 330 subjects with amphetamine toxicity treated with an antipsychotic, there were two episodes of coma and QT prolongation and one episode of each: hypotension, NMS, cardiac arrest, and death.ConclusionThis systematic review represents an exhaustive compilation of the available evidence. There is neither a clear benefit of antipsychotics over benzodiazepines nor a definitive signal of harm noted. We encourage clinicians to adapt treatment based on specific circumstances and characteristics of their individual patients.