Elihu D. Richter

Relationship between conflicts of interest and research results

AbstractCONTEXT: To date, research regarding the influence of conflicts of interest on the presentation of findings by researchers has been limited. OBJECTIVE: To evaluate the sources of funding for published manuscripts, and association between reported findings and conflicts of interest. METHODS: Data from both print and electronic issues of The New England Journal of Medicine (NEJM) and The Journal of the American Medical Association (JAMA) were analyzed for sources of funding, areas of investigation, conflict of interest (COI), and presentation of results. We reviewed all original manuscripts published during the year 2001 within NEJM (N=193) and JAMA (N=205). We use 3 definitions for COI in this paper: a broadly defined criterion, the criterion used by The International Council of Medical Journal Editors (ICMJE), and a criterion defined by the authors. RESULTS: Depending on the COI criteria used, 16.6% to 32.6% of manuscripts had 1 or more author with COI. Based on ICMJE criterion, 38.7% of studies investigating drug treatments had authors with COI. We observed a strong association between those studies whose authors had COI and reported positive findings (P < .001). When controlling for sample size. study design, and country of primary authors, we observed a strong association between positive results and COI (ICMJE definition) among all treatment studies (adjusted odds ratio [OR], 2.35; 95% confidence interval [CI], 1.08 to 5.09) and drug studies alone (OR, 2.64; 95% CI, 1.09 to 6.39). CONCLUSION: COI is widespread among the authors of published manuscripts and these authors are more likely to present positive findings.

Phthalate exposure among pregnant women in Jerusalem, Israel: Results of a pilot study

BACKGROUND Phthalates can disrupt endocrine function and induce reproductive and developmental toxicity in laboratory animals. Few studies have evaluated exposure to phthalates in pregnant women, despite the potential sensitivity of the developing fetus to adverse effects of phthalates. METHODS We measured urinary concentrations of 11 phthalate metabolites in 19 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups and used the Mann-Whitney U-test for independent samples to determine significant differences between groups. RESULTS Nine metabolites were detected in at least 95% of the samples: mono(2-ethyl-5-carboxypentyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(n-butyl) phthalate, monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), mono(2-ethylhexyl) phthalate and monoisobutyl phthalate. Phthalate metabolite concentrations in these pregnant women were remarkably similar to those in the general United States female population. MBzP geometric mean concentrations were higher in women living in buildings existing 40 years or more (P=0.04). In women who used four or more personal care products (perfume, deodorant, lipstick, nail polish, or hand/face cream) in the 48 h prior to providing the urine sample, geometric mean MEP concentrations were more than 4 times higher than concentrations in women using only two or three of the aforementioned products (P=0.07). CONCLUSIONS Pregnant women in Jerusalem are exposed to a wide range of phthalates. Building materials used in old constructions may be a source of exposure to benzylbutyl phthalate, the parent compound of MBzP. Personal care products may be sources of exposure to diethyl phthalate, the parent compound of MEP.

Amyotrophic Lateral Sclerosis in a Battery-factory Worker Exposed to Cadmium

Abstract A 44-year-old patient died from amyotrophic lateral sclerosis (ALS) after nine years of heavy exposure to cadmium (Cd) in a nickel-cadmium (Ni-Cd) battery factory. Two years after starting work he and co-workers had experienced pruritus, loss of smell, nasal congestion, nosebleeds, cough, shortness of breath, severe headaches, bone pain, and proteinuria. Upper back pain and muscle weakness progressed to flaccid paralysis. EMG findings were consistent with motor neuron disease. Cd impairs the blood-brain barrier, reduces levels of brain copper-zinc (Cu–Zn) superoxide dismutase (SOD), and enhances excitoxicity of glutamate via up-regulation of glutamate dehydrogenase and down-regulation of glutamate uptake in glial cells. High levels of methallothionein, a sign of exposure to heavy metals, have been found in brain tissue of deceased ALS patients. The effects of Cd on enzyme systems that mediate neurotoxicity and motor neuron disease suggest a cause-effect relationship between Cd and ALS in this worker.

Long-term effects of repealing the national maximum speed limit in the United States

OBJECTIVES We examined the long-term effects of the 1995 repeal of federal speed limit controls on road fatalities and injuries in fatal crashes. METHODS We used a Poisson mixed-regression model to assess changes in the number of fatalities and injuries in fatal crashes between 1995 and 2005 on rural interstates, where all US states have raised speed limits since the repeal, as well as on urban interstates and noninterstate roads, where many states have raised speed limits. RESULTS We found a 3.2% increase in road fatalities attributable to the raised speed limits on all road types in the United States. The highest increases were on rural interstates (9.1%) and urban interstates (4.0%). We estimated that 12 545 deaths (95% confidence interval [CI] = 8739, 16 352) and 36 583 injuries in fatal crashes (95% CI = 29 322, 43 844) were attributable to increases in speed limits across the United States. CONCLUSIONS Reduced speed limits and improved enforcement with speed camera networks could immediately reduce speeds and save lives, in addition to reducing gas consumption, cutting emissions of air pollutants, saving valuable years of productivity, and reducing the cost of motor vehicle crashes.

Cancer in radar technicians exposed to radiofrequency/microwave radiation: sentinel episodes.

Abstract Controversy exists concerning the health risks from exposures to radiofrequency/microwave irradiation (RF/MW). The authors report exposure-effect relationships in sentinel patients and their co-workers, who were technicians with high levels of exposure to RF/MW radiation. Information about exposures of patients with sentinel tumors was obtained from interviews, medical records, and technical sources. One patient was a member of a cohort of 25 workers with six tumors. The authors estimated relative risks for cancer in this group and latency periods for a larger group of self-reported individuals. Index patients with melanoma of the eye, testicular cancer, nasopharyngioma, non-Hodgkins lymphoma, and breast cancer were in the 20–37-year age group. Information about work conditions suggested prolonged exposures to high levels of RF/MW radiation that, produced risks for the entire body. Clusters involved many different types of tumors. Latency periods were extremely brief in index patients and a larger self reported group. The findings suggest that young persons exposed to high levels of RF/MW radiation for long periods in settings where preventive measures were lax were at increased risk for cancer. Very short latency periods suggest high risks from high-level exposures. Calculations derived from a linear model of dose-response suggest the need to prevent exposures in the range of 10-100 μw/cm2.

Raised speed limits, case fatality and road deaths: a six year follow-up using ARIMA models

Background: In November 1993, the Israeli government increased the speed limit for all vehicles from 90 to 100 km per hour on a total of 115 km of its three major interurban highways. Design/Setting: We use ARIMA time series intervention models to evaluate the effect of the raise in speed limit on fatalities, serious injuries, and case-fatality for years 1988–1999. Motor vehicle crash data came from the Central Bureau of Statistics of Israel. Results: Between January 1988 and December 1999, a total of 6029 persons were killed and 45 616 were seriously injured on roads in Israel. For all roads combined, the time series ARIMA model indicated that there were 4.69 more deaths per month (p<0.001), or 347 more than expected in the post-intervention period. Case-fatality rate (CFR) on all roads combined rose significantly (p<0.001). Modified case-fatality rate (CFRS) showed an increase of 2.5 deaths per 100 serious casualties (p<0.001). Conclusions: The impact of raised speed limits was immediate and sustained. The largest increase in deaths occurred on interurban roads but a spillover effect was observed on urban roads as well. The increases in deaths and case-fatality rates persisted six years after the speed limit change despite major countermeasures and increasing congestion throughout the period of follow-up.

Death and injury from motor vehicle crashes in Colombia

We report data on the distribution and determinants of road deaths and injuries for all victims in Colombia, with the aim of defining targets and priorities for highway death prevention in that country and other rapidly urbanizing nations. Using information from Colombias Fund for the Prevention of Road Injury and the national death registry, we studied data on deaths and injuries from 1991 to 1995 for the nation as a whole and for the countrys two largest cities, Santa Fe de Bogotá and Medellín. Deaths and injuries are rising in the nation as a whole. Of the deaths, 75% occur in urban areas, and 80% are in males. Pedestrians aged 15-34 are a peak subgroup. Thirty-four percent of deaths are attributable to speeding and/or alcohol consumption. Death tolls are highest at night and on weekends. Specific priority targets for intervention are indicated by the fact that 75% of road deaths in Colombia occur in urban areas and that 80% of all victims are males.

Chronic Ammonia Inhalation and Interstitial Pulmonary Fibrosis: A Case Report and Review of the Literature

Ammonia is an irritant gas with a characteristic pungent odor, which is widely used in industry. Inasmuch as ammonia is highly soluble in water and, upon inhalation, is deposited in the upper airways, occupational exposures to ammonia have commonly been associated with sinusitis, upper airway irritation, and eye irritation. Acute exposures to high levels of ammonia have also been associated with diseases of the lower airways and interstitial lung. In this study, the authors report on a patient with long-term, repetitive occupational exposure to ammonia at levels at or above odor recognition who developed interstitial lung disease. The scientific literature on inhaled ammonia exposure is reviewed and discussed. The authors conclude that the taking of a careful occupational exposure history for patients presenting with shortness of breath associated with ammonia exposure may assist with an early diagnosis, thus allowing for treatment early in the disease process and prevention of further exposure.

Childhood lead exposure in the palestinian authority, Israel, and Jordan : Results from the middle eastern regional cooperation project, 1996-2000

In the Middle East, the major sources of lead exposure have been leaded gasoline, lead-contaminated flour from traditional stone mills, focal exposures from small battery plants and smelters, and kohl (blue color) in cosmetics. In 1998–2000, we measured blood lead (PbB) levels in children 2–6 years of age in Israel, Jordan, and the Palestinian Authority (n = 1478), using a fingerstick method. Mean (peak; percentage > 10 μg/dL) PbB levels in Israel (n = 317), the West Bank (n = 344), Jordan (n = 382), and Gaza (n = 435) were 3.2 μg/dL (18.2; 2.2%), 4.2 μg/dL (25.7; 5.2%), 3.2 μg/dL (39.3; < 1%), and 8.6 μg/dL (> 80.0; 17.2%), respectively. High levels in Gaza were all among children living near a battery factory. The findings, taken together with data on time trends in lead emissions and in PbB in children in previous years, indicate the benefits from phasing out of leaded gasoline but state the case for further reductions and investigation of hot spots. The project demonstrated the benefits of regional cooperation in planning and carrying out a jointly designed project.

Cancer in Ex-Asbestos Cement Workers in Israel, 1953-1992

A cohort of 3,057 male workers employed in an asbestos-cement plant using 90% chrysotile-10% crocidolite, located in Northern Israel, was followed from 1953-1992 for incidence and mortality from cancer. In the years 1978-1992, the cohort had an elevated risk for all malignant neoplasms combined (n = 153, SIR = 117, ns), lung cancer (n = 28, SIR = 135, ns), mesothelioma (n = 21; SIR > 5000, p < .0001), unspecified pleural cancer (n = 5; SIR = 278, P < .0001), and liver cancer (n = 7, SIR 290, ns). Risks for colo-rectal (n = 19; SIR = 79, ns), bladder (n = 12, SIR 69) and renal cancers (n = 5, SIR 104) were less than expected. Risk for mesothelioma showed a sharp risk gradient with duration of exposure, increasing from 1 per 625 for those employed less than 2 years to 1 per 4.5 workers employed over 30 years. The ratio of mesothelioma to excess lung cancer cases was 2.9 to 1, or 3.6 to 1, if pleural cases of unspecified origin were included; the pleura to peritoneum ratio of verified mesothelioma cases was 20 to 1. This atypically high ratio of mesothelioma to excess lung cancer cases is suggested to be the combined result of high past asbestos exposures in the workers and their low prior risk for lung cancer, and possibly, relatively early smoking cessation in relation to asbestos exposure.