Ascertaining causes of neonatal deaths using verbal autopsy: current methods and challenges.

OBJECTIVE: 'Verbal autopsy' (VA) is used to ascertain cause of death in countries where vital registration systems are lacking. Current VA methods for neonatal deaths vary widely and suffer from several limitations. We aimed to: (1) review current neonatal VA methods, (2) identify gaps and limitations, (3) illustrate some limitations using VA data and (4) identify new approaches in methodology and analysis. STUDY DESIGN: Rolling techniques and database search terms were used to identify articles that described neonatal VA administration, validation and cause of death assignment. RESULT: Current VA interviews include open and close-ended modules and are administered by trained interviewers. Causes of death are determined using physician review and/or computer algorithms for various neonatal causes of death. Challenges include lack of a standardized VA instrument and administration of methods, difficulty in identifying gold standards for validation studies, lack of validated algorithms for causes of death, poor existing algorithms, lack of standardized death classification terminology and the use of hierarchy to assign causes of death. Newer probabilistic methods of analysis such as Bayes Theorem or the Symptom Pattern method may improve accuracy for cause of death estimation and alleviate some of the challenges with traditional physician and algorithmic approaches, although additional research is needed. CONCLUSION: Given the continued reliance on VA to determine cause of death in settings with inadequate registration systems, it is important to understand the gaps in current VA methods and explore how methods can be improved to accurately reflect neonatal disease burden in the global community.

Factors constraining adherence to referral advice for severely ill children managed by the Integrated Management of Childhood Illness approach in Imbabura Province, Ecuador.

AIM: Low referral completion rates in developing countries undermine the Integrated Management of Childhood Illness (IMCI) strategy for lowering child mortality. This study sought to identify factors constraining adherence to referral advice in a health system using the IMCI approach. METHODS: Caregivers of 160 children urgently referred to hospital were prospectively interviewed. Caregivers who accessed and did not access hospital were compared for potential referral constraining factors, including demographics, family dynamics, the severity of their child's illness, their interaction with the health system, self-perceived problems, and physical and financial access. RESULTS: 67/160 (42%) referred children did not access hospital. Six factors were associated with non-access, including two health worker actions: not being given a referral slip [adjusted odds ratio (OR)= 15.3, 95% confidence interval (95% CI) 4.4-64.6] and not being told to go to the hospital immediately (adjusted OR = 5.3, 95% CI 1.9-16.3). Receiving both of these interventions reduced the risk of not accessing hospital to 19%, from 96% for those who received neither intervention. Several indicators of illness severity, including caregivers' ranking of their children's illness severity, the presence of severe illness signs and mortality, were investigated and found not to be important explanatory factors. CONCLUSION: Providing a referral slip and counseling the caregivers of severely ill children to go to the hospital immediately appear to be powerful tools for increasing successful referral outcomes.

Antimicrobial susceptibilities and serotype distribution of Streptococcus pneumoniae isolates from a Low socioeconomic area in Lima, Peru.

Streptococcus pneumoniae isolates were obtained from nasopharyngeal swabs taken from children living in a low socioeconomic area of Lima, Peru, to determine the rates of antimicrobial resistance and serotype distribution. A total of 146 nasopharyngeal isolates were collected from children from 3 to 38 months of age. Twenty-one clinical laboratory isolates from both sterile and nonsterile sites were obtained from a local hospital. Isolates with reduced susceptibilities to penicillin represented 15.1 and 42.9% of the nasopharyngeal and clinical isolates, respectively. For neither group of isolates did penicillin MICs exceed 1.5 micro g/ml, indicating only intermediate resistance. Thirty-two different serotypes were identified from the 146 nasopharyngeal isolates. The serotypes of the clinical isolates were represented among those 32 types. Isolates with reduced susceptibility to multiple antimicrobial agents were present in both settings. These findings indicate some of the highest rates of antimicrobial resistance in the region as well as a slightly different serotype distribution pattern from those of other South American countries. The 7-valent conjugate pneumococcal vaccines would only have a limited effect, providing coverage for about half of all isolates. Increasing rates of resistance in Peru necessitate an awareness of antimicrobial treatment practices and vaccination strategies.

Diagnosis and management of febrile children using the WHO/UNICEF guidelines for IMCI in Dhaka, Bangladesh.

OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible.

Validation of caregiver interviews to diagnose common causes of severe neonatal illness.

The objective of this study was to validate retrospective caregiver interviews for diagnosing major causes of severe neonatal illness and death. A convenience sample of 149 infants aged < 28 days with one or more suspected diagnoses of interest (low birthweight/severe malnutrition, preterm birth, birth asphyxia, birth trauma, neonatal tetanus, pneumonia, meningitis, septicaemia, diarrhoea, congenital malformation or injury) was taken from patients admitted to two hospitals in Dhaka, Bangladesh. Study paediatricians performed a standardised history and physical examination and ordered laboratory and radiographic tests according to study criteria. With a median interval of 64.5 days after death or hospital discharge, caregivers of 118 (79%) infants were interviewed about their child's illness. Using reference diagnoses based on predefined clinical and laboratory criteria, the sensitivity and specificity of particular combinations of signs (algorithms) reported by the caregivers were ascertained. Sufficient numbers of children with five reference standard diagnoses were studied to validate caregiver reports. Algorithms with sensitivity and specificity > 80% were identified for neonatal tetanus, low birthweight/severe malnutrition and preterm delivery. Algorithms with specificities > 80% for birth asphyxia and pneumonia had sensitivities < 70%, or alternatively had high sensitivity with lower specificity. In settings with limited access to medical care, retrospective caregiver interviews provide a valid means of diagnosing several of the most common causes of severe neonatal illness and death.

PIP: This study aimed to validate retrospective caregiver interviews for diagnosing major causes of several neonatal illness and death in Dhaka, Bangladesh. The sample consisted of 149 infants aged 28 days with one or more suspected diagnoses of low birth weight (LBW)/severe malnutrition, preterm birth, birth asphyxia, birth trauma, neonatal tetanus, pneumonia, meningitis, septicemia, diarrhea, congenital malformation or injury. The study pediatricians performed a standardized history and physical examination and ordered laboratory and radiographic tests according to study criteria. Overall, LBW/severe malnutrition, premature birth and tetanus can be detected in newborn infants by caregiver interview with high sensitivity and specificity, whereas the diagnoses of pneumonia and birth asphyxia are more difficult but still feasible. Algorithms with sensitivity and specificity 80% were identified for neonatal tetanus, LBW/severe malnutrition and preterm delivery. Algorithms with specificities 80% for birth asphyxia and pneumonia had sensitivities 70%, or alternatively had high sensitivity with lower specificity. In settings with limited access to medical care, retrospective caregiver interviews provide a valid means of diagnosing several of the most common causes of severe neonatal illness and death.

Potential implications of the integrated management of childhood illness (IMCI) for hospital referral and pharmaceutical usage in western Uganda.

The integrated management of childhood illness approach (IMCI) is currently being implemented by a number of countries worldwide. This is the second report from a study in western Uganda comparing the assessment and classification of disease by medical assistants using the IMCI algorithm with that of hospital-based general medical officers, who used their clinical judgement to assess and provide treatment. Treatment prescribed by the hospital medical officers was compared to that indicated by IMCI disease classifications. The study population comprised 1226 children aged 2-59 months. Medical assistants had some difficulty in completing the IMCI assessment, leading to incorrect classification of findings in 138 of 1086 completed forms (13%). If their classifications had been used to decide on hospital referral, 37 children who met IMCI criteria for referral would have been sent home. Consultations took on average 7.2 min, longer than usual for several African countries. Use of the IMCI guidelines would have referred 16.2% of children to hospital, compared with 22% referred by the medical officers. Use of IMCI could have reduced the cost of medication to US$0.17 per child compared to the treatment cost of US$0.82 as prescribed by medical officers. Medical officers prescribed both a greater number and a greater variety of drugs than indicated by the IMCI algorithm. Compared to the present management of sick children by medical officers at Kabarole district hospital, using the IMCI algorithm would bring major changes in pharmaceutical use and referral practices. However, there is concern about the difficulty medical assistants had in using it, and the potential for longer consultation times.

Decrease in infant mortality in New York City after 1989.

OBJECTIVES: This study identified factors contributing to the rapid decline in infant mortality in New York City from 1989 to 1992. METHODS: Changes in birthweight distributions and in birthweight/age-, cause-, and birthweight/age/cause-specific mortality rates from 1988/89 (before the mortality reduction) to 1990/91 were identified from New York City vital statistics data. RESULTS: Infant, neonatal, and postneonatal mortality of very-low-birthweight (< 1500 g) and normal-birthweight infants decreased significantly. The declines were almost entirely due to decreases in birthweight-specific mortality rates, rather than increased birthweights. All races experienced most of these reductions. Mortality decreased significantly for 6 causes of death. These decreases were consistent with the birthweight/age groups experiencing mortality declines. CONCLUSIONS: Widespread, multiple perinatal and postnatal factors contributed to the decline in infant mortality.

Identifying sick children requiring referral to hospital in Bangladesh.

The object of this study was to evaluate and improve the guidelines for the Integrated Management of Childhood Illness (IMCI) with respect to identifying young infants and children requiring referral to hospital in an area of low malaria prevalence. A total of 234 young infants (aged 1 week to 2 months) and 668 children (aged 2 months to 5 years) were prospectively sampled from patients presenting at a children's hospital in Dhaka, Bangladesh. The study paediatricians obtained a standardized history and carried out a physical examination, including items in the IMCI guidelines developed by WHO and UNICEF. The paediatricians made a provisional diagnosis and judged whether each patient needed hospital admission. Using the paediatrician's assessment of a need for admission as the standard, the sensitivity and specificity of the current and modified IMCI guidelines for correctly referring patients to hospital were examined. The IMCI's sensitivity for a paediatrician's assessment in favour of hospital admission was 84% (95% confidence interval (CI): 75-90) for young infants and 86% (95% CI: 81-90) for children, and the specificity was, respectively, 54% (95% CI: 45-63) and 64% (95% CI: 59-69). One fourth or more in each group had a provisional diagnosis of pneumonia, and the IMCI's specificity was increased without lowering sensitivity by modifying the respiratory signs calling for referral. These results show that the IMCI has good sensitivity for correctly referring young infants and children requiring hospital admission in a developing country setting with a low prevalence of malaria. The guidelines' moderate specificity will result in considerable over-referral of patients not needing admission, thereby decreasing opportunities for successful treatment of patients at first-level health facilities. The impact of the IMCI guidelines on children's health and the health care system must be judged in the light of current treatment practices, health outcomes and referral patterns.

PIP: Findings are presented from a study conducted to evaluate and improve the integrated management of childhood illness (IMCI) training program guidelines on identifying young infants and children who need to be referred to hospitals in an area of low malaria prevalence. 234 infants aged 1 week to 2 months and 668 children aged 2 months to 5 years were prospectively sampled from patients who presented at a children's hospital in Dhaka, Bangladesh. Pediatricians obtained standardized histories from the patients and conducted a physical examination. The IMCI's sensitivity relative to a pediatrician's assessment in favor of hospital admission was 84% for young infants and 86% for children, while specificities were 54% and 64%, respectively. 25% or more of both young infants and children were provisionally diagnosed with pneumonia. The IMCI's specificity increased without reducing sensitivity by changing the respiratory signs demanding referral. Study findings indicate that the IMCI is sensitive enough to result in the proper referral of young infants and children in need of hospital admission in a developing country setting with a low prevalence of malaria.

The integrated management of childhood illness in western Uganda.

Bringing together various disease-specific guidelines for sick children, WHO and UNICEF have developed an Integrated Management of Childhood Illness (IMCI) algorithm, one component of which (assess and classify) was tested in the outpatient department of a rural district hospital in western Uganda. Children aged 2-59 months were seen first by a Ugandan medical assistant trained in IMCI, and then evaluated by a medical officer. Sensitivity, specificity and positive predictive values were determined by comparing the IMCI classifications with a reference standard based on the medical officers' diagnoses and laboratory tests. Of the 1226 children seen, 69% were classified into more than one symptom category, 7% were not classified in any symptom category, 8% had a danger sign, and 16% were classified into a severe category, for which the IMCI approach recommended urgent hospital referral. Specificity for most classifications was good, though sensitivity and positive predictive values were variable. We conclude that the IMCI algorithm is an important advance in the primary care of sick children in developing countries.

PIP: The World Health Organization (WHO) and UNICEF have developed the Integrated Management of Childhood Illness (IMCI) algorithm which incorporates the existing guidelines for the management of diarrhea and respiratory diseases, and adds new guidelines for measles, malaria, malnutrition, and anemia into one comprehensive case management approach. The assessment and classification component of the algorithm was tested in the outpatient department of a rural district hospital in western Uganda. 1226 children aged 2-59 months were first seen by a Ugandan medical assistant trained in IMCI, then evaluated by a medical officer. Sensitivity, specificity, and positive predictive values were determined by comparing the IMCI classifications with a reference standard based upon the medical officers' diagnoses and laboratory tests. 69% of the 1226 children seen were classified into more than one symptom category, 7% were not classified into any category, 8% had a danger sign, and 16% were classified into a severe category. The IMCI approach recommends that patients in this latter, severe category be urgently referred for hospital care. While specificity for most classifications was good, sensitivity and positive predictive values were variable. The IMCI algorithm is, however, an important advance in the primary care of sick children in developing countries.

Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria.

The object of this study was to assess the ability of pallor and other clinical signs, including those in the Integrated Management of Childhood Illness (IMCI) guidelines developed by WHO and UNICEF, to identify severe anaemia and some anaemia in developing country settings with and without malaria. A total of 1226 and 668 children aged 2 months to 5 years were prospectively sampled from patients presenting at, respectively, a district hospital in rural Uganda and a children's hospital in Dhaka, Bangladesh. The study physicians obtained a standardized history and carried out a physical examination that included pallor, signs of respiratory distress, and the remaining IMCI referral signs. The haematocrit or haemoglobin level was determined in all children with conjunctival or palmar pallor, and in a sample of the rest. Children with a blood level measurement and assessment of pallor at both sites were included in the anaemia analysis. Using the haematocrit or haemoglobin level as the reference standard, the correctness of assessments using severe and some pallor and other clinical signs in classifying severe and some anaemia was determined. While the full IMCI process would have referred most of the children in Uganda and nearly all the children in Bangladesh with severe anaemia to hospital, few would have received a diagnosis of severe anaemia. Severe palmar and conjunctival pallor, individually and together, had 10-50% sensitivity and 99% specificity for severe anaemia; the addition of grunting increased the sensitivity to 37-80% while maintaining a reasonable positive predictive value. Palmar pallor did not work as well as conjunctival pallor in Bangladesh for the detection for severe or some anaemia. Combining "conjunctival or palmar pallor" detected 71-87% of moderate anaemia and half or more of mild anaemia. About half the children with no anaemia were incorrectly classified as having "moderate or mild" anaemia. Anaemia was more easily diagnosed in Uganda in children with malaria. Our results show that simple clinical signs can correctly classify the anaemia status of most children. Grunting may serve as a useful adjunct to pallor in the diagnosis of severe anaemia. Conjunctival pallor should be added to the IMCI anaemia box, or the guidelines need to be adapted in regions where palmar pallor may not readily be detected.

PIP: The capability of pallor and other clinical signs to identify anemia was evaluated in developing country settings with malaria (Uganda) and without malaria (Bangladesh). Enrolled were 1226 children, 2 months to 5 years of age, who presented to a rural district hospital in Fort Portal, Uganda, and 668 children from a children's hospital in Dhaka, Bangladesh. Physicians examined the children for conjunctival pallor, respiratory distress, and other clinical signs of anemia (i.e., palmar pallor) included in the World Health Organization's Integrated Management of Childhood Illness (IMCI) guidelines. 58% of Ugandan and 47% of Bangladeshi children had pallor of at least one site. Hematocrit or hemoglobin levels were measured in all children with pallor of the conjunctiva or palms and in a sample of the remaining children. In both locations, 2% of children had severe anemia; 13% and 17%, respectively, in Uganda and Bangladesh had moderate anemia, and 42% and 62%, respectively, had mild anemia. Comparison of these findings with the clinical signs indicated that use of the full IMCI process would have referred 68-90% of children with severe anemia to the hospital. Severe palmar and conjunctival pallor, individually and together, had a sensitivity of 10-50% and a specificity of 99% for severe anemia; the addition of grunting increased the sensitivity to 37-80% while maintaining a reasonable positive predictive value. Palmar pallor was not as effective as conjunctival pallor for detecting anemia in Bangladesh. Combining conjunctival and palmar pallor detected 71-87% of cases of moderate anemia and half the cases of mild anemia. Anemia was more easily diagnosed in Uganda in children with malaria. These findings confirm the usefulness of clinical signs in the detection of anemia in developing countries, but suggest the feasibility of adding conjunctival pallor, and possibly grunting, to the IMCI algorithm.

Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria

The object of this study was to assess the ability of pallor and other clinical signs, including those in the Integrated Management of Childhood Illness (IMCI) guidelines developed by WHO and UNICEF, to identify severe anaemia and some anaemia in developing country settings with and without malaria. A total of 1226 and 668 children aged 2 months to 5 years were prospectively sampled from patients presenting at, respectively, a district hospital in rural Uganda and a children's hospital in Dhaka, Bangladesh. The study physicians obtained a standardized history and carried out a physical examination that included pallor, signs of respiratory distress, and the remaining IMCI referral signs. The haematocrit or haemoglobin level was determined in all children with conjunctival or palmar pallor, and in a sample of the rest. Children with a blood level measurement and assessment of pallor at both sites were included in the anaemia analysis. Using the haematocrit or haemoglobin level as the reference standard, the correctness of assessments using severe and some pallor and other clinical signs in classifying severe and some anaemia was determined. While the full IMCI process would have referred most of the children in Uganda and nearly all the children in Bangladesh with severe anaemia to hospital, few would have received a diagnosis of severe anaemia. Severe palmar and conjunctival pallor, individually and together, had 10-50% sensitivity and 99% specificity for severe anaemia; the addition of grunting increased the sensitivity to 37-80% while maintaining a reasonable positive predictive value. Palmar pallor did not work as well as conjunctival pallor in Bangladesh for the detection for severe or some anaemia. Combining "conjunctival or palmar pallor" detected 71-87% of moderate anaemia and half or more of mild anaemia. About half the children with no anaemia were incorrectly classified as having "moderate or mild" anaemia. Anaemia was more easily diagnosed in Uganda in children with malaria. Our results show that simple clinical signs can correctly classify the anaemia status of most children. Grunting may serve as a useful adjunct to pallor in the diagnosis of severe anaemia. Conjunctival pallor should be added to the IMCI anaemia box, or the guidelines need to be adapted in regions where palmar pallor may not readily be detected

Validation of the diagnosis of childhood morbidity using maternal health interviews.

The diagnosis of childhood illness by maternal health interview surveys is widely used to estimate the prevalence of childhood morbidity in developing countries. To determine the validity of interview-based diagnoses, and to define simple, sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers during structured interviews with physicians' diagnoses for 271 children on the Philippine island of Cebu. The 271 children had 318 physician diagnosed illnesses: 105 acute lower respiratory infections (ALRI), 121 diarrhoeas, 36 measles, 50 upper respiratory infections (URTI), 5 roseola infantums and one milaria rubria. An algorithm for measles (age greater than or equal to 120 days, rash and fever greater than or equal to 3 days and fading of rash) had a sensitivity and specificity of 94%. For ALRI an algorithm of cough, dysponea and fever had a sensitivity of 82%, but specificity was lower in comparison with URTI (58%) than with children who had no respiratory illness (79%). Inclusion of signs of respiratory distress (flaring of nostrils, intercostal retraction) raised the specificity to 83-84%, but reduced sensitivity to 68%. Diagnosis of diarrhoea based on frequent loose or liquid stools had a sensitivity of 95-97% and specificity of 80% in children with or without concomitant non-diarrhoeal illnesses. Addition of questions on numbers of stools (greater than or equal to 6 per day), and no signs of dehydration increased specificity to 95% but reduced the sensitivity to 84-86%. However, specific signs of dehydration were not well reported by the mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of ethanol abuse in the etiology of heroin-related death.

Toxicology analyses and other forensic science data were used to examine the mechanisms through which ethanol increased the risk for death caused by injected street preparations of heroin. The authors studied 505 victims of fatal heroin overdose and compared subjects who had concentrations of blood ethanol greater than 1000 mg/L (n = 306) with those who had concentrations less than, or equal to 1000 mg/L (n = 199). We found significant negative correlations between concentrations of ethanol and morphine (a heroin metabolite) in blood (R2 = 0.11, P = 0.0001 for log10-transformed variables) as well as between concentrations of blood ethanol and bile morphine (R2 = 0.16, P = 0.0001 for log10 bile morphine versus blood morphine). Toxicologic evidence of infrequent heroin use was more common in decedents with blood ethanol concentrations greater than 1000 mg/L than in those with lower concentrations. Our data suggest that ethanol enhances the acute toxicity of heroin, and that ethanol use indirectly influences fatal overdose through its association with infrequent (nonaddictive) heroin use and thus with reduced tolerance to the acute toxic effects of heroin.

Validation of postmortem interviews to ascertain selected causes of death in children.

In developing countries, diagnoses of diseases associated with deaths in children are frequently derived from retrospective maternal interviews. To determine the validity of this methodology, and to define sensitive and specific diagnostic algorithms, we compared symptoms and signs reported by mothers using structured questionnaires, with selected physician diagnoses for 164 deaths among hospitalized children on the Philippine island of Cebu. The 164 decreased children had 256 physician diagnoses of acute lower respiratory infections (ALRI) (100), diarrhoeas (92), measles (48), and neonatal tetanus cases (16). Forty-three per cent of children had multiple illnesses. An algorithm for tetanus (age at death less than or equal to 30 days with convulsion or spasm) was 100% sensitive, but specificity could not be estimated due to the small number of comparison neonatal deaths. An algorithm for measles (age greater than or equal to 120 days, with rash and fever for at least three days) had 98% sensitivity and 90% specificity. Diagnosis of ALRI was more difficult, cough and dyspnoea alone yielding 86% sensitivity but low specificity, whereas prolonged cough and dyspnoea provided 93% specificity but low sensitivity (41%). Diarrhoea diagnoses based on frequent loose or liquid stools had high sensitivity (78-84%) and specificity (79%), irrespective of whether the child died with diarrhoea alone or in combination with other illnesses. However, maternal reports of moderate/severe dehydration had low specificity. We conclude that, in this setting, verbal autopsies can diagnose major illnesses contributing to death in children with acceptable sensitivity and specificity.

Temporal clustering of heroin overdoses in Washington, DC.

During the 5-day period from 28 Feb. 1985 through 4 March 1985, 24 heroin overdoses occurred in the District of Columbia. Statistical tests for clustering of fatal and nonfatal overdoses during this interval identified 7 heroin-related deaths that occurred on March 1 to 2 as a statistically significant cluster (p = 0.007). An extension of the analysis for clustering to a 15-month period identified 2 additional clusters, 1 of fatal overdoses and 1 of nonfatal ones. When all victims of fatal overdose in cluster intervals were combined and compared with all other heroin-related deaths, no significant differences were noted for levels of morphine or ethanol in blood. However, bile morphine concentrations of cluster decedents were significantly lower than those of noncluster decedents (p = 0.033), suggesting that these decedents were less tolerant to the effects of narcotics than the comparison group. Heroin concentrations in street-level heroin samples collected during clusters did not differ from those collected during comparison intervals. These data conflict with the traditional explanation of overdose clusters, which attributes these events to unusually potent street-level heroin.