Common Mode Of Death Research Articles

Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study.

Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16 years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54 months (interquartile range 28-111), 25 (28%) patients had 53 appropriate therapies [ICD shock n = 45, anti-tachycardia pacing (ATP) n = 8], incidence rate 4.7 per 100 patient years (95% CI 2.9-7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n = 4, ATP n = 4), incidence rate 1.1/100 patient years (95% CI 0.4-2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n = 15) and infection (n = 10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication. In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

Clinical outcomes and programming strategies of implantable cardioverter defibrillator (ICD) devices during childhood in hypertrophic cardiomyopathy: a UK national cohort study

Abstract Background Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). ICDs have been shown to be effective at terminating malignant ventricular arrhythmias but at the expense of a high incidence of complications. The optimal device and programming strategies to reduce complications in this patient group are unknown. Purpose To describe the programming strategies and clinical outcomes of ICD implantation in childhood HCM. Methods Anonymised, non-invasive clinical data were collected from a retrospective, longitudinal multi-centre cohort of children (&amp;lt;16 years) with HCM (n=687) and an ICD in-situ from the United Kingdom. Results 96 patients (61 male (64%), 6 non-sarcomeric (6%)) underwent ICD implantation at a median age 14yr (IQR 11–16, range 3–16) and weight 52.3 kg (IQR 34.8–63.1). Indication for ICD was primary prevention in 72 (75%). 82 (85%) had an endovascular system, 3 (3%) epicardial and 11 (12%) subcutaneous system. 61 patients (74%) were receiving one or more cardioactive medications at implantation [B blockers n=66, 70%, disopyramide n=14, 15%, amiodarone n=7, 7%, calcium channel blocker n=7, 9%, other n=5, 6%]. Programming practices varied: all had VF therapies activated (median 220bpm, IQR 212–230); 70 (73%) had a VT zone programmed (median rate 187 bpm, SD 20.9), of which 26 (27%) had therapies activated. 50 patients (61%) had antitachycardia pacing (ATP) activated. Over a median follow up of 53.6 months (IQR 27.3,108.4), 4 patients (4.2%) died following arrhythmic events despite a functioning device. 25 patients had 53 appropriate therapies (ICD shock n=47, ATP n=8), incidence rate 5.22 (95% CI 3.5–7.8). On univariable analysis, secondary prevention indication for ICD implantation was the only predictor of therapy [16 (64%) vs 8 (11.3%), p value &amp;lt;0.001]. 8 (8.3%) patients had 9 inappropriate therapies (ICD shock n=4, ATP n=5), incidence rate 1.37 (95% CI 0.65–2.8), caused by T wave oversensing (n=2), lead migration (n=1), supraventricular tachycardia (n=1). Device complications were seen in 30 patients (31%), including lead complications (n=16) and infection (n=10). No clinical characteristics predicted time to inappropriate therapy or lead complication. Conclusions In a contemporary cohort of children with HCM, the incidence of inappropriate therapies is lower than previously reported, yet complication rates remain higher than reported in adult patients. No clinical, device or programming strategies were associated with inappropriate therapies or lead complications. Funding Acknowledgement Type of funding source: Other. Main funding source(s): British Heart Foundation

The relationship between left ventricular outflow tract gradient and sudden cardiac death in childhood hypertrophic cardiomyopathy

Abstract Background The most common mode of death in childhood hypertrophic cardiomyopathy (HCM) is sudden cardiac death (SCD). Left ventricular outflow tract obstruction (LVOTO) is an established risk factor for SCD in adults with the disease. In contrast, the prognostic implications of LVOTO in childhood disease is unclear, with recent studies suggesting that it may have an inverse relationship with the risk of SCD. Purpose The aim of this study was to explore the role of LVOTO and the risk of SCD in childhood HCM. Methods A multi-centre, retrospective, longitudinal cohort of 871 children (diagnosed with HCM &amp;lt;16 years of age) was used to explore the relationship between SCD and LVOTO (LVOT gradient ≥30mmHg). Results 189 patients (23%) had LVOTO, which was mild (30–50mmHg), moderate (50–100mmHg) or severe (&amp;gt;100mmHg) in 58 (6.7%), 98 (11.3%) and 33 (3.8%), respectively. The risk of SCD showed an inverse relation to LVOT gradient severity compared to those with no obstruction: mild HR 1.75 (95% CI 0.89–3.44), moderate HR 1.04 (95% 0.55–1.98), and severe HR 0.7 (0.36–1.35) [figure].On univariable analysis [table] LVOTO was associated with heart failure symptoms (NYHA&amp;gt;1) [p &amp;lt;0.001], maximal wall thickness (MWT) [p &amp;lt;0.001], left atrial (LA) diameter [p &amp;lt;0.001], and future myectomy occurring during follow up [p &amp;lt;0.001]. The inverse relationship observed was not altered by the presence or absence of other traditional risk factors. Conclusions LVOTO appears to have a complex relationship with the risk of SCD in childhood HCM, with multiple contributing factors. The pathophysiological mechanisms behind this observation need further exploration, which may be limited by low patient numbers Cummulative incidence of SCD by LVOTO Funding Acknowledgement Type of funding source: Other. Main funding source(s): British Heart Foundation

Rodenticide Poisoning: Critical Appraisal of Patients at a Tertiary Care Center.

ABSTRACTImportanceRodenticide poisoning is a common occurrence in India. Of the different classes of rodenticides available, yellow phosphorus is considered highly toxic. There are scarce epidemiological data regarding the ingestion of yellow phosphorus in the subcontinent.ObjectivesThis study aimed to identify the clinical profile of rodenticide-poisoned patients and delineate mortality predictors.DesignProspective observational study.Setting and participantsStudy was conducted at the Department of Internal Medicine, Government Villupuram Medical College and Hospital. All adult inpatients with a history of rodenticide poison exposure were eligible participants. A total of 99 patients completed the study protocol.Main outcomeSurvival with or without morbidity and death.ResultsIn all, 90.91% of patients consumed the paste formulation of rodenticide [yellow phosphorus (67.2%) and yellow phosphorus + zinc phosphide (24%)].The time to resuscitation showed significance to mortality. Survival rate among patients instituted gastric decontamination within 2 hours of exposure (97.87%) was significantly higher than those who were not (84.62%) (p = 0.033). The clinical picture revealed conspicuous absence of signs and symptoms during the first 24 hours. In all, 72.73% (n = 72) manifested with toxidrome after a lag period of 24–36 hours (range 18–72 hours). The dominant clinical manifestations included abdominal pain (52.53%), jaundice (22.21%), coagulopathy (15.15%), encephalopathy (10.10%), shock (10.10%), acute kidney injury (AKI; 7.08%), and multi-organ failure (17.17%). Laboratory data showed elevated aspartate transaminase (AST; 48.47%), alanine aminotransferase (ALT; 49.50%), bilirubin levels (22.21%), metabolic acidosis (10.12%), serum creatinine (7.08%), prothrombin time prolongation (PT/INR; 15.15%), and activated partial thromboplastin time (aPTT) (3.30%). The mortality was 9.1% (n = 9) of which 77.78% (n = 7) died of fulminant hepatic failure. The mean time for death was 4.22 days since exposure (range 2–8 days).ConclusionRodenticide poisoning in Southern India is dominated by yellow phosphorus. In this study, we identified delayed resuscitation, jaundice, hepatic encephalopathy, elevation of AST and ALT to >1000 IU/L, metabolic acidosis, and refractory shock as reliable predictors of bad outcome in this patient population. The common mode of death was fulminant hepatic failure.RelevanceRodenticide poisoning ranks second in mortality hierarchy at our institute, and systematic analysis of this patient population is an urgent need.How to cite this articleGopalakrishnan S, Kandasamy S, Iyyadurai R. Rodenticide Poisoning: Critical Appraisal of Patients at a Tertiary Care Center. Indian J Crit Care Med 2020;24(5):295–298.

227A novel risk prediction model for sudden cardiac death in childhood hypertrophic cardiomyopathy (HCM Risk-Kids)

Abstract Background Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM) but there is no validated algorithm to identify those at highest risk. This study sought to develop and validate a SCD risk prediction model that provides individualized risk estimates. Methods A prognostic model was derived from an international, retrospective, multi-center longitudinal cohort study of 1024 consecutively evaluated patients aged ≤16 years. The model was developed using pre-selected predictor variables [unexplained syncope, maximal left ventricular (LV) wall thickness (MWT), left atrial diameter (LAD), LV outflow tract (LVOT) gradient and non-sustained ventricular tachycardia (NSVT)] identified from the literature and internally validated using bootstrapping. Results Over a median follow up of 5.3 years (IQR 2.6, 8.2, total patient years 5984), 89 (8.7%) patients died suddenly or had an equivalent event [annual event rate 1.49 (95% CI 1.15–1.92)]. The pediatric model was developed using pre-selected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; C-statistic was 0.69 (95% CI 0.66–0.72) and the calibration slope was 0.98 (95% CI 0.58–1.38). For every 10 ICDs implanted in patients with ≥6% 5-year SCD risk, potentially 1 patient will be saved from SCD at 5 years. Conclusions This new validated risk stratification model for SCD in childhood HCM provides accurate individualized estimates of risk at 5 years using readily obtained clinical risk factors. Acknowledgement/Funding British Heart Foundation

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids)

Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. To develop and validate an SCD risk prediction model that provides individualized risk estimates. A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Heart Failure with Preserved Ejection Fraction is a Highly Arrhythmogenic Disease

Background Sudden cardiac death (SCD) is a relatively common mode of death in patients with heart failure preserved ejection fraction (HFpEF). However, the spectrum and burden of cardiac arrhythmias, particularly those of ventricular arrhythmias, has not well established in these patients. Methods We performed routine arrhythmia surveillance using a 14-day adhesive patch ambulatory ECG recorder (ZioPatch) in patients with HFpEF, enrolled in a subspecialty heart failure clinic. Cardiac electrophysiologists interpreted the ECG recordings. We extracted the clinical data from electronic medical records. Results A total of 40 patients (mean age 71.1±9.9 years, 53% women) with HFpEF underwent routine Ziopatch monitoring. Mean ejection fraction was 59.4±4.4% and 44% had history of coronary artery disease. Of the 40 patients, 32.5% had episodes of non-sustained ventricular tachycardia (VT) (mean 5±5.2 episodes), 15.0% had paroxysmal atrial fibrillation and 80.0% had episodes of supraventricular tachycardia during the monitored period. All patients had premature ventricular complexes (PVC) with 7.5% having a PVC burden that exceeded 5%. Patients with non-sustained VT had a relatively lower EF, higher NT-proBNP level and were more likely to be obese (Table). Conclusion Patients with HFpEF have a high, and possibly underappreciated, burden of cardiac arrhythmias. The frequent episodes of non-sustained VT in these patients may provide insight into the mechanism of SCD in HFpEF.

Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction

BackgroundAlthough heart failure with preserved ejection fraction (HFpEF) is considered a disease of the elderly, younger patients are not spared from this syndrome. ObjectivesThis study therefore investigated the associations among age, clinical characteristics, and outcomes in patients with HFpEF. MethodsUsing data on patients with left ventricular ejection fraction ≥45% from 3 large HFpEF trials (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function], I-PRESERVE [Irbesartan in Heart Failure With Preserved Systolic Function], and CHARM Preserved [Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity]), patients were categorized according to age: ≤55 years (n = 522), 56 to 64 years (n = 1,679), 65 to 74 years (n = 3,405), 75 to 84 years (n = 2,464), and ≥85 years (n = 398). This study compared clinical and echocardiographic characteristics, as well as mortality and hospitalization rates, mode of death, and quality of life across age categories. ResultsYounger patients (age ≤55 years) with HFpEF were more often obese, nonwhite men, whereas older patients with HFpEF were more often white women with a higher prevalence of atrial fibrillation, hypertension, and chronic kidney disease (eGFR <60 ml/min/1.73 m2). Despite fewer comorbidities, younger patients had worse quality of life compared with older patients (age ≥85 years). Compared with patients age ≤55 years, patients age ≥85 years had higher mortality (hazard ratio: 6.9; 95% confidence interval: 4.2 to 11.4). However, among patients who died, sudden death was, proportionally, the most common mode of death (p < 0.001) in patients age ≤55 years. In contrast, older patients (age ≥85 years) died more often from noncardiovascular causes (34% vs. 20% in patients age ≤55 years; p < 0.001). ConclusionsCompared with the elderly, younger patients with HFpEF were less likely to be white, were more frequently obese men, and died more often of cardiovascular causes, particularly sudden death. In contrast, elderly patients with HFpEF had more comorbidities and died more often from noncardiovascular causes. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302; Irbesartan in Heart Failure With Preserved Systolic Function [I-PRESERVE]; NCT00095238; Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712)

Modes of death and clinical outcomes in adult patients with hypertrophic cardiomyopathy in Thailand

BackgroundThere are limited data about modes of death and major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM) in South East Asian population. The aim of the study was to examine modes of death and clinical outcomes in Thai patients with HCM.MethodsBetween January 1, 2009 and December 31, 2013, 166 consecutive patients with HCM diagnosed in our institution were evaluated. Five patients were excluded because of non-Thai ethnic groups (n = 3) and diagnosis of myocardial infarction at initial presentation documented by coronary angiography (n = 2). The final study population consisted of 161 patients with HCM. HCM-related deaths included: (1) sudden cardiac death (SCD) – death due to sudden cardiac arrest or unexpected sudden death; (2) heart failure – death due to refractory heart failure; or (3) stroke - death due to embolic stroke associated with atrial fibrillation. MACEs included: (1) SCD, sudden unexpected aborted cardiac arrest, fatal, or nonfatal ventricular arrhythmia (ventricular fibrillation or sustained ventricular tachycardia); (2) heart failure (fatal or non-fatal), or heart transplantation; or (3) stroke - fatal or non-fatal embolic stroke associated with atrial fibrillation.ResultsOne hundred and sixty-one Thai patients with HCM (age 66 ± 16 years, 58% female) were enrolled. Forty-two patients (26%) died over a median follow-up period of 6.8 years including 25 patients (16%) with HCM-related deaths (2%/year). The HCM-related deaths included: heart failure (52% of HCM-related deaths; n = 13), SCD (44% of HCM-related deaths; n = 11), and stroke (4% of HCM-related deaths, n = 1). The SCDs occurred in 6.8% of patients (1%/year). Eighty-four major MACEs occurred in 65 patients (41, 5%/year). The MACEs included: 40 heart failures in which 2 patients underwent heart transplants; 22 SCDs and nonfatal ventricular arrhythmias; and 22 fatal or nonfatal strokes.ConclusionsThe most common mode of death in adult patients with HCM in Thailand was heart failure followed by SCD. About one-third of the patients experiencing heart failure died during the 6.8 years of follow-up. SCDs occurred in 7% of patients (1%/year), predominantly in the fourth decade or later.

PC-FACS

PC-FACS

Epidemiology of Cause of Death in Pediatric Acute Respiratory Distress Syndrome.

Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia. Retrospective, decedent-only analysis. Two large, academic PICUs. Nonsurvivors with pediatric acute respiratory distress syndrome. None. Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3-13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a neurologic cause, including brain death. Patients dying greater than or equal to 7 days after pediatric acute respiratory distress syndrome onset were more commonly immunocompromised. Multisystem organ failure predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was the most common mode of death at all timepoints, accounting for 66% of all deaths. Organ dysfunction was common at time of death, irrespective of cause of death. Refractory hypoxemia accounted for only a minority of pediatric acute respiratory distress syndrome deaths (20%). In pediatric acute respiratory distress syndrome, early deaths were due primarily to neurologic failure, whereas later deaths were more commonly due to multisystem organ failure. Deaths from neurologic causes accounted for a substantial portion of nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our study highlights limitations associated with using death as an endpoint in therapeutic pediatric acute respiratory distress syndrome trials.

Low serum chloride in patients with chronic heart failure: clinical associations and prognostic significance.

Low serum chloride is common in patients with chronic heart failure (CHF) and is associated with worse outcomes. We investigated the clinical and prognostic associations, including cause of death associations, of low serum chloride in patients referred to a secondary care clinic with suspected heart failure. Patients with echocardiogram and serum chloride were evaluated (n = 5613). CHF was defined as signs and symptoms of the disease and either left ventricular systolic dysfunction (LVSD) worse than mild [heart failure with reduced ejection fraction (HFrEF)] or LVSD mild or better and raised amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L) [heart failure with preserved ejection fraction (HFpEF)]. Hypochloraemia was defined as greater than two standard deviations below the mean in the local normal distribution (<96 mmol/L). Of the 5613 patients referred, 908 patients did not have CHF, 1988 had HFrEF, and 2717 had HFpEF. Compared to patients in the fourth quartile (median chloride 106 mmol/L), patients in the first quartile (median chloride 96 mmol/L) had more severe symptoms (38% New York Heart Association class III or IV vs. 25%, P < 0.001) and were more likely to take loop diuretics (79% vs. 55%, P < 0.001). The annual mortality rate for patients with CHF was 11%. Hypochloraemia was associated with an increased risk of death independent of NT-proBNP. Patients in the first quartile had a two-fold increased risk of death compared to patients in the fourth quartile (P < 0.001). Sudden death was a common mode of death amongst patients with hypochloraemia. Hypochloraemia is strongly related to an adverse prognosis and may be a therapeutic target in patients with CHF.

A one-year retrospective study on the pattern of death found at autopsy at Forensic Pathology Department, Menelik II Hospital in Addis Ababa, Ethiopia

Background: The main objectives of this study were to determine the magnitude, manner and modalities of natural and unnatural deaths among deaths brought to the Forensic Pathology Department. Menelik II Hospital, for post mortem examination and secondary to find the remedial measures that may have influence on the incidence of preventable deaths. Methods: This retrospective study was conducted in the Department of Forensic Pathology at Menelik II Hospital, Addis Ababa, Ethiopia. From January 1 st , 2014 to December 31 st , 2014. The Study material was collected from Forensic Pathology Department of Menelik II Hospital, postmortem reports. A total of 4206 cases of deaths were done postmortem examination during the one-year study period. All these cases were grouped according to age, gender, manners and modalities of natural and unnatural deaths. The data collected was analyzed. Results: Out of total 4206 cases, the male to female ratio 3:1. The age group most commonly involved was 16-30 years (41,5%) followed by 31-55 years (38,3%). Only 7.8% were in the under 15years age group. The commonest mode of death in all age groups put together was accident in 1615 (38.4%) followed by natural death in 1156 (27.5%), homicidal deaths accounted for 698 (16.6%) followed by suicide in 508 (12%). In 229 (5.4%) of the cases the manner of death remained undetermined. Among 698 homicidal deaths, blunt weapon injury accounted for 61.4% and bullet injury were in 15.4%. Among the accidental deaths, road traffic injuries were 1092 (67.6%), followed by fall accident in 170 (10.5%). Hanging was the preferred modality of suicide (88.4%), followed by poisoning 51 (10%). Natural death accounted for 1190 (27.5%) and cardiac disease was the most predominant 453 (38%), followed by respiratory disease 240 (20.2%). Conclusion: Our study concludes that unnatural deaths exceeded enormously the natural deaths. Accident was the most dominant manner of death among the unnatural deaths. Road Traffic Accident was the commonest modality among accidental deaths. Fatalities caused by blunt weapon injuries were the commonest mode of homicide; whereas hanging was the preferred modality of suicide. Cardiovascular diseases were the leading causes of natural deaths. Most deaths are preventable, so concerned bodies are expected to take action of prevention and increase the public awareness of the real situation and the causes of both natural and unnatural deaths and subsequently make an impact in the decrement of death rate in our societies.

Reference values of lithium in postmortem femoral blood

IntroductionThe main recipients of lithium, people diagnosed with bipolar disorder, show an increased mortality in both natural and unnatural causes of death. Based on international data persons diagnosed with bipolar disorder comprise 2.3–9.6% of all suicidal deaths. In cases of suicide among those suffering from bipolar disorder, 17–53% are due to fatal intoxications. Diagnosing fatal intoxications is often challenging, particularly when the reference information needed to interpret the concentration of a drug is lacking or scarce. AimThe aim of this study was to establish postmortem femoral blood reference concentrations of lithium, providing both fatal and “normal” postmortem concentrations, as well as to investigate the impact of the mode of intoxication and to study the co-detection of lithium and antidepressant drugs in intoxications and controls. MethodIn Sweden, forensic autopsies are performed in unnatural and obscure deaths. This study included all autopsies in which lithium was found during the study period (1992–2010). Lithium was not included in the regular drug screen, but analysed upon request using flame photometry, ion-selective electrode detection or atomic absorption spectrophotometry. Each case was evaluated according to an established strategy, with strict inclusion and exclusion criteria followed by a multi-observer manual review (Fig. 1, Table 1). The cases included were classified as single intoxications (group A), multi-drug intoxications (group B) or controls (group C). The control group only included cases where death by intoxication and antemortem incapacitation by drugs could be ruled out. Results and discussionDuring the study period, lithium was found in 124 cases. After application of inclusion and exclusion criteria and the subsequent manual review, 21 cases were classified as group A (n=4), group B, (n=7) and group C (n=10). The femoral blood lithium concentrations in group A (median 2.69mmol/l) and group B (median 2.10mmol/l) were significantly different (p=0.01) compared to group C (median 0.2mmol/l). There were however no statistically significant difference between the concentrations in groups A and B. The most common mode of death in intoxications was acute-on-chronic (n=10), but the impact of chronic use on the fatal blood concentrations could not be evaluated since there was just one case without previous use. There was no difference in the proportion of co-detections of lithium and antidepressants between intoxication cases and controls.

MiR-19b Regulates Ventricular Action Potential Duration in Zebrafish.

Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome.

Gag Deadens but doesn't Mute the Crime: a Case Series of Homicidal Gagging

Background : Asphyxia is the commonest mode of death in various violent homicidal deaths and in majority of such cases, there may not be any evidence of external injury except the general features of asphyxia being the only proof to rely upon. Under such circumstances, even an experienced medicolegal expert may not go further than to declare the death to be due to asphyxia; the exact mode adopted being left unexplained. Case Report: We present here a case report of three family members who were killed by means of gagging with the motive of taking over the property. Conclusion: Deaths due to gagging is rare but most of the times homicidal. This case was peculiar as there were multiple individuals who were gagged simultaneously and their bodies were stuffed into trunk.

Eclapmsia: The Major Cause of Maternal Mortality in Eastern India.

Eclampsia is a very serious complication of pregnancy which is responsible for high maternal and perinatal mortality. Worldwide, it accounts for 50,000 maternal deaths annually. In spite of several global and regional interventions and initiatives from governments and other concerned agencies, maternal mortality is still very high in India, with eclampsia as a major cause. This study was conducted to determine the mode of deaths and incidence of maternal mortality associated with eclampsia and to assess how socio-demographic and clinical characteristics of the women influence the deaths. This is a retrospective study of 111 eclampsia related maternal deaths over a period of 5 years from January 2008 to December 2012. Data pertaining to their age, parity, booking status, gestational age at delivery, and time interval from admission to death were also obtained from the records for analysis. Eclampsia accounted for 43.35% of total maternal deaths, with case fatality of 4.960%. The commonest mode of death in eclampsia is pulmonary oedema. Death due to eclampsia commonly occurs in younger age group of 19-24 years and in primi gravid. Eclampsia related deaths were mostly seen in illiterate and unbooked cases. Maternal deaths were also very common in lower socio economic status. Eclampsia still remains the major cause of maternal mortality in this region resulting from unsupervised pregnancies and deliveries. There is a need to educate and encourage the general public for antenatal care and hospital delivery by which we can defeat this powerful enemy.

Autopsy study of febrile deaths during monsoon at a tertiary care institute in India: Is malaria still a challenge?

Background:To utilise an autopsy-based approach to study the febrile deaths and deaths due to malaria during monsoon period of three years at a tertiary care teaching hospital in Mumbai, India.Materials and Methods:All autopsies done at the hospital during monsoon period from 2005 to 2007 when fever was the main presenting symptom were included in the study. Monsoon period was defined from June to September. A study on the duration of hospital stay of malaria deaths was also attempted.Results:There were 202 autopsies of febrile illness during the study period. Malaria resulted in 20.8% of the deaths besides other causes. A majority of deaths had intrapulmonary haemorrhages as the only pathological finding. Incidence of malaria deaths was more during monsoon period than the non-monsoon period. Plasmodium falciparum was the most common species responsible for malaria deaths while cerebral malaria was the most common mode of death. In 27% of the cases, post-mortem examination helped to arrive at the correct final diagnosis. In 88.1% of the cases, malaria deaths occurred within the first 24 hours of admission to the hospital.Conclusion:The study reiterates the fact that malaria remains a preventable but major cause of death in India, predominantly during the monsoon period. The study also emphasises the importance of developing treatment protocols for malaria during such crucial times besides reinforcing the existing preventive measures.

Comprehensive Study of Unnatural Deaths in Females of Age Group 15–45 years in Allahabad

A significant number of unnatural deaths of females occur in the age group of 15–45 years because this is the age when young girls or women have to go through the important changes of their lives such as education, marriage, job, family responsibility etc. A prospective cross-sectional study was carried out between 11 April 2012 to 10 April 2013 at mortuary, S.R.N. Hospital, Allahabad with the main aim of determining various epidemiological aspects, causes and manner of unnatural deaths of females in the age group of 15–45 years. Amongst 2857 autopsies performed during the study period, 864 (30.24%) victims were female. Amongst 864 female victims, 593 (68.63%) females were in the age group studied. The age group of 15–25 years included maximum number of deaths (54.13%) in study sample (n=593). Burns was the most common mode of death. Septicaemic shock was the most common cause of death (47.96%). Unnatural deaths were highest in Hindu females (78.07%) and higher in rural (71.84%) than in urban (28.16%) areas. Out of 467 married females, 241 (51.61%) died within 7 years of their marriage, most probably due to widely prevalent evil of ‘dowry death’ in India. Accident was the most common manner of death (46.37%). A comprehensive study was done revealing the need of various socio-cultural and legal measures to be taken to handle the grave results of this study.

Biomarkers of Myocardial Stress and Fibrosis as Predictors of Mode of Death in Patients With Chronic Heart Failure

The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure. The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death. Prediction of the mode of death may facilitate treatment decisions. The relationship between amino-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3, and ST2, biomarkers that reflect different pathogenic pathways in heart failure (myocardial stress and fibrosis), and mode of death is unknown. HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction (left ventricular ejection fraction≤35%). An independent clinical events committee prospectively adjudicated mode of death. NT-proBNP, galectin-3, and ST2 levels were assessed at baseline in 813 subjects. Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling, and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death. Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP. After a median follow-up period of 2.5 years, there were 155 deaths: 49 from pump failure, 42 from sudden cardiac death, and 64 from other causes. Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses. In each case, increases in the biomarker had a stronger association with pump failure than sudden cardiac death, but this relationship was attenuated after adjustment for clinical risk factors. Clinical variables along with NT-proBNP levels were stronger predictors of pump failure (C statistic: 0.87) than sudden cardiac death (C statistic: 0.73). Addition of ST2 and galectin-3 led to improved net risk classification of 11% for sudden cardiac death, but not pump failure. Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk, with insignificant incremental contributions of ST2 and galectin-3. Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers.