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1.  Does Donating Blood for the First Time During a National Emergency Create a Better Commitment to Donating Again? 
Vox sanguinis  2009;98(3 Pt 1):e219-e224.
Background and Objectives
Emergency situations often elicit a generous response from the public. This occurred after attacks on the US on September 11, 2001 when many new blood donors lined up to donate. This study was performed to compare return rates for first time donors (FTD) after September 11th, 2001 to FTD during a comparable period in 2000.
Materials and Methods
3315 allogeneic whole blood donations from FTD at a regional blood center were collected between September 11th and 30th, 2001. Subsequent donations by the FTD before March 31, 2002 were reviewed. This (test) group was compared to 1279 FTD(control group) donating during the same time period in September 2000 and to their return rate in the subsequent six months.
Following September 11, 2001, 1087/3315 (32.8%) FTD returned by March 31, 2002. This return rate was similar to the control group (427/1279 (33.4%)). The deferral rate during the donor screening process for the control group was significantly higher than the deferral rate for the September 11–30, 2001 group (p < 0.01). The odds of an individual FTD returning increased with age, and the chance of a female donor returning was 1.13 times higher than a male (p = 0.06). There was a carryover effect after Sept. 11, 2001 too.
A national emergency, September 11, 2001, inspired people to donate blood for the first time. However, the proportion of return donations amongst them was not increased. Females and males in certain age groups were more likely to become repeat donors due to the residual effect of September 11, 2001. Additional efforts are needed to retain eligible FTD in donor pools.
PMCID: PMC2859095  PMID: 20002621
blood donor; donor retention; national emergency; 9/11
2.  Estimating the Time Interval Between Exposure to the World Trade Center Disaster and Incident Diagnoses of Obstructive Airway Disease 
American Journal of Epidemiology  2014;180(3):272-279.
Respiratory disorders are associated with occupational and environmental exposures. The latency period between exposure and disease onset remains uncertain. The World Trade Center (WTC) disaster presents a unique opportunity to describe the latency period for obstructive airway disease (OAD) diagnoses. This prospective cohort study of New York City firefighters compared the timing and incidence of physician-diagnosed OAD relative to WTC exposure. Exposure was categorized by WTC arrival time as high (on the morning of September 11, 2001), moderate (after noon on September 11, 2001, or on September 12, 2001), or low (during September 13–24, 2001). We modeled relative rates and 95% confidence intervals of OAD incidence by exposure over the first 5 years after September 11, 2001, estimating the times of change in the relative rate with change point models. We observed a change point at 15 months after September 11, 2001. Before 15 months, the relative rate for the high- versus low-exposure group was 3.96 (95% confidence interval: 2.51, 6.26) and thereafter, it was 1.76 (95% confidence interval: 1.26, 2.46). Incident OAD was associated with WTC exposure for at least 5 years after September 11, 2001. There were higher rates of new-onset OAD among the high-exposure group during the first 15 months and, to a lesser extent, throughout follow-up. This difference in relative rate by exposure occurred despite full and free access to health care for all WTC-exposed firefighters, demonstrating the persistence of WTC-associated OAD risk.
PMCID: PMC4108044  PMID: 24980522
change point model; latency; obstructive airway disease; occupational exposure; rescue/recovery workers; World Trade Center
3.  Adherence to HIV medications in a cohort of men who have sex with men: Impact of September 11th 
Adherence to highly active antiretroviral therapy (HAART) regimens remains a challenge for people living with human immunodeficiency virus (HIV). Severe traumas like that of September 11, 2001, can exacerbate the difficulties already associated with adherence. A community-based sample of 68 HIV-seropositive men who have sex with men (MSM) living in New York City who were on protease inhibitor HAART regimens completed quantitative assessments to examine adherence in the aftermath of September 11th. Data were drawn from a larger study of drug use and HIV medication adherence. Assessments conducted from September 24, 2001 to October 24, 2001 were compared to assessments taken 2–4 months prior to September 11th. Repeated measures analyses of variance were used to analyze the number of missed and suboptimal doses (doses taken outside the prescribed time by ±4 hours) reported in the 2 weeks prior to each respective assessment. The results indicated a significant increase in the number of missed doses and the number of suboptimal doses immediately after the events of September 11th. Differences in adherence were not influenced, however, by sociodemographic characteristics. These results suggest that the events of September 11th had an impact on adherence to HIV medications among MSM in New York City and provide further support for the notion that the events of September 11th may have adversely impacted the lives of seropositive individuals. Attention should be paid by clinicians working with HIV-positive individuals on how this event has been incorporated into lives of individuals already burdened by a chronic and demanding disease.
PMCID: PMC3456102  PMID: 12612105
Adherence; Drug users; HIV; MSM; Terrorism
4.  Exposures among Pregnant Women near the World Trade Center Site on 11 September 2001 
Environmental Health Perspectives  2005;113(6):739-748.
We have characterized environmental exposures among 187 women who were pregnant, were at or near the World Trade Center (WTC) on or soon after 11 September 2001, and are enrolled in a prospective cohort study of health effects. Exposures were assessed by estimating time spent in five zones around the WTC and by developing an exposure index (EI) based on plume reconstruction modeling. The daily reconstructed dust levels were correlated with levels of particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5; r = 0.68) or PM10 (r = 0.73–0.93) reported from 26 September through 8 October 2001 at four of six sites near the WTC whose data we examined. Biomarkers were measured in a subset. Most (71%) of these women were located within eight blocks of the WTC at 0900 hr on 11 September, and 12 women were in one of the two WTC towers. Daily EIs were determined to be highest immediately after 11 September and became much lower but remained highly variable over the next 4 weeks. The weekly summary EI was associated strongly with women’s perception of air quality from week 2 to week 4 after the collapse (p < 0.0001). The highest levels of polycyclic aromatic hydrocarbon–deoxyribonucleic acid (PAH-DNA) adducts were seen among women whose blood was collected sooner after 11 September, but levels showed no significant associations with EI or other potential WTC exposure sources. Lead and cobalt in urine were weakly correlated with ∑EI, but not among samples collected closest to 11 September. Plasma OC levels were low. The median polychlorinated biphenyl level (sum of congeners 118, 138, 153, 180) was 84 ng/g lipid and had a nonsignificant positive association with ∑EI (p > 0.05). 1,2,3,4,6,7,8-Heptachlorodibenzodioxin levels (median, 30 pg/g lipid) were similar to levels reported in WTC-exposed firefighters but were not associated with EI. This report indicates intense bystander exposure after the WTC collapse and provides information about nonoccupational exposures among a vulnerable population of pregnant women.
PMCID: PMC1257600  PMID: 15929898
dust; exposure index; metal; PAH; particulate; PBDE; PCB; polychlorinated dibenzodioxins; polychlorinated dibenzofurans; pregnant; WTC; WTC plume
5.  Distribution of a Population of Rhizobium leguminosarum bv. trifolii among Different Size Classes of Soil Aggregates† 
A combination of the plant infection-soil dilution technique (most-probable-number [MPN] technique) and immunofluorescence direct count (IFDC) microscopy was used to examine the effects of three winter cover crop treatments on the distribution of a soil population of Rhizobium leguminosarum bv. trifolii across different size classes of soil aggregates (<0.25, 0.25 to 0.5, 0.5 to 1.0, 1.0 to 2.0, and 2.0 to 5.0 mm). The aggregates were prepared from a Willamette silt loam soil immediately after harvest of broccoli (September 1995) and before planting and after harvest of sweet corn (June and September 1996, respectively). The summer crops were grown in soil that had been either fallowed or planted with a cover crop of red clover (legume) or triticale (cereal) from September to April. The Rhizobium soil population was heterogeneously distributed across the different size classes of soil aggregates, and the distribution was influenced by cover crop treatment and sampling time. On both September samplings, the smallest size class of aggregates (<0.25 mm) recovered from the red clover plots carried between 30 and 70% of the total nodulating R. leguminosarum population, as estimated by the MPN procedure, while the same aggregate size class from the June sampling carried only ∼6% of the population. In June, IDFC microscopy revealed that the 1.0- to 2.0-mm size class of aggregates from the red clover treatment carried a significantly greater population density of the successful nodule-occupying serotype, AR18, than did the aggregate size classes of <0.5 mm, and 2 to 5 mm. In September, however, the population profile of AR18 had shifted such that the density was significantly greater in the 0.25- to 0.5-mm size class than in aggregates of <0.25 mm and >1.0 mm. The populations of two other Rhizobium serotypes (AR6 and AS36) followed the same trends of distribution in the June and September samplings. These data indicate the existence of structural microsites that vary in their suitabilities to support growth and protection of bacteria and that are influenced by the presence and type of plant grown in the soil.
PMCID: PMC106353  PMID: 16349531
6.  Preterm Delivery in Boston Before and After September 11th, 2001 
Epidemiology (Cambridge, Mass.)  2005;16(3):323-327.
We hypothesized that stress induced by the terrorist attacks of September 11, 2001 might shorten pregnancy. To test this hypothesis, we compared gestational duration and risk of preterm delivery among women who were pregnant on September 11 with women who had delivered before that date.
Study Design
We conducted a matched cohort study among pregnant women enrolled in the Boston-based cohort study Project Viva between 1999 and 2001. Each of 606 participants, pregnant on September 11, 2001, was matched to 1 or 2 participants who delivered before that date.
Compared with women who delivered before September 11th, women who were pregnant on September 11th had mean gestation length that was 0.13 weeks longer (95% confidence interval = −0.05 to 0.30) and an odds ratio for preterm delivery before 37 weeks’ gestation of 0.60 (0.36 to 0.98). Only women exposed in the first trimester had longer gestation.
Contrary to expectation, Boston-area women who were pregnant on September 11th had a lower risk of preterm delivery than women who delivered before that date. Although the interpretation of this finding is difficult, it is clear that the acute psychologic stress documented nationwide after the terrorist attacks did not increase the risk of preterm delivery in this population at some distance from the attacks.
PMCID: PMC1994912  PMID: 15824547
7.  Heat Acclimatization in Hot Summer for Ten Weeks Suppress the Sensitivity of Sweating in Response to Iontophoretically-administered Acetylcholine 
To determine the peripheral mechanisms involved in thermal sweating during the hot summers in July before acclimatization and after acclimatization in September, we evaluated the sweating response of healthy subjects (n=10) to acetylcholine (ACh), a primary neurotransmitter involved in peripheral sudomotor sensitivity. The quantitative sudomotor axon reflex test (QSART) measures sympathetic C fiber function after iontophoresed ACh evokes a measurable reliable sweat response. The QSART, at 2 mA for 5 min with 10% ACh, was applied to determine the directly activated (DIR) and axon reflex-mediated (AXR) sweating responses during ACh iontophoresis. The AXR sweat onset-time by the axon reflex was 1.50±0.32 min and 1.84±0.46 min before acclimatization in July and after acclimatization in September, respectively (p<0.01). The sweat volume of the AXR(1) [during 5 min 10% iontophoresis] by the axon reflex was 1.45±0.53 mg/cm2 and 0.98±0.24 mg/cm2 before acclimatization in July and after acclimatization in September, respectively (p<0.001). The sweat volume of the AXR(2) [during 5 min post-iontophoresis] by the axon reflex was 2.06±0.24 mg/cm2 and 1.39±0.32 mg/cm2 before and after acclimatization in July and September, respectively (p<0.001). The sweat volume of the DIR was 5.88±1.33 mg/cm2 and 4.98±0.94 mg/cm2 before and after acclimatization in July and September, respectively (p<0.01). These findings suggest that lower peripheral sudomotor responses of the ACh receptors are indicative of a blunted sympathetic nerve response to ACh during exposure to hot summer weather conditions.
PMCID: PMC2788658  PMID: 19967078
Heat acclimatization; Sweating; QSART; ACh
8.  Cardiac events in New Jersey after the September 11, 2001, terrorist attack 
The higher stress associated with the World Trade Center (WTC) attacks on September 11, 2001, may have resulted in more cardiac events particularly in those living in close proximity. Our goal was to determine if there was an increase in cardiac events in a subset of emergency departments (EDs) within a 50-mi radius of the WTC. We performed a retrospective analysis of consecutive patients seen by ED physicians in 16 EDs for the 60 days before and after September 11 in 2000–2002. We determined the number of patients admitted to an inpatient bed with a primary or secondary diagnosis of acute myocardial infarction (MI) or tachyarrhythmia. In each year, we compared patient visits for the 60 days before and after September 11 using the chi-square statistic. For the 360 days during the 3 years, there were 571,079 patient visits in the database of which 110,766 (19.4%) were admitted. Comparing the 60 days before and after September 11, 2001, we found a statistically significant increase in patients with MIs (79 patients before versus 118 patients after, P=.01), representing an increase of 49%. There were no statistically significant differences for MIs in 2000 and 2002 and in tachyarrhythmias for all three years. For the 60-day period after September 11, 2001, we found a statistically significant increase in the number of patients presenting with acute MI but no increase in patients admitted with tachyarrhythmias.
PMCID: PMC3456051  PMID: 16000653
Acute myocardial infarction; Emergency care; Tachyarrhythmia; Terrorism
9.  Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States 
PLoS Medicine  2006;3(10):e401.
The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States.
Methods and Findings
We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r2 = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r2 = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season.
We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.
Influenza timing and spread in the US from 1996 to 2005 was influenced by the volume of domestic and international air travel. The flight ban after September 11, 2001, was associated with a delayed and prolonged influenza season.
Editors' Summary
In both the northern and southern hemispheres, influenza epidemics occur annually during the winter “flu season.” Although the disease maps out a remarkably similar pattern in most years, little is known about the specific mechanisms by which geographic spread occurs. Given the perennial possibility of influenza global epidemics (pandemics) such as occurred in 1918, 1957, and 1969, as well as the more recent, localized outbreaks of avian influenza (“bird flu”) in which a high proportion of affected people have died, we need to understand how influenza spreads in order to limit the destructive impact of future pandemics.
Why Was This Study Done?
In theory, airline travel might be expected to play a role in the spread of influenza across large distances. If so, reducing or restricting air travel might be an appropriate public health intervention in the early stages of an influenza pandemic. This study was performed to identify specific effects of air travel on the annual spread of influenza in the United States.
What Did the Researchers Do and Find?
The researchers analyzed weekly government records on deaths from influenza and pneumonia in cities from nine regions of the US during the nine influenza seasons between 1996 and 2005. For each year, they determined the time it took for the epidemic to spread across the US and the date of the national peak in influenza deaths. They then used government estimates of passenger air travel to explore any connection with the timing of the annual flu epidemics.
The analysis found that the usual time for an influenza epidemic to reach peak levels across the US was approximately two weeks, and that the national peak date fell within two days of the average date, February 17, in five of the nine seasons. In general, influenza was found to spread more slowly during years when the number of domestic air travelers, particularly during November, was lower. Also, the peak of the influenza season was found to come later during years when the number of international air travelers, particularly in September, was lower. These results, based on reported deaths from pneumonia or influenza, were corroborated using data from an influenza virus surveillance program, and could not be explained by variations in winter temperatures or by different types of influenza virus circulating in different years.
Of note, the peak date of the US influenza season following September 11, 2001, was delayed by 13 days to March 2, consistent with marked reductions in airline travel following the terrorist attack, and then returned to February 17 over the subsequent two influenza seasons as international airline travel returned to its previous levels. In contrast, the investigators found no delay in the 2001–2002 influenza season in France, where flight restrictions were not imposed.
What Do These Findings Mean?
While this study does not demonstrate that travel restriction would be effective in altering the course of a flu pandemic, it does provides evidence that air travel plays a significant role in the annual spread of influenza in the United States. Although other factors, related or unrelated to the decrease in air travel after September 11, may have affected the course of the 2001–2002 influenza season, the general findings across several years suggest that air travel affects both the peak date and the rate of spread of influenza. These findings merit consideration in the process of preparing for the next influenza pandemic.
Additional Information.
Please access these Web sites via the online version of this summary at
World Health Organization: influenza pandemic preparedness page
US Department of Health and Human Services: avian and pandemic flu information site
Wikipedia page on influenza pandemic (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
PMCID: PMC1564183  PMID: 16968115
10.  Protective effect of inactivated hepatitis A vaccine against the outbreak of hepatitis A in an open rural community 
AIM: To evaluate the protective effect of inactivated hepatitis A vaccine (Healive®) against hepatitis A outbreak in an emergency vaccination campaign.
METHODS: During an outbreak of hepatitis A in Honghe Town, Xiuzhou District, Jiaxing City, Zhejiang Province, two nonrandomized controlled trials were conducted in September 2006. The first trial was to vaccinate 108 anti-HAV negative individuals with close contacts of the patients from September with 1 dose of an inactivated hepatitis A vaccine, Healive®. The control group comprised of 115 individuals with close contacts of the patients before September. The second trial was to vaccinate 3365 primary and secondary school students who volunteered to receive a dose of Healive® and 2572 students who did not receive Healive® serving as its controls. An epidemiological survey was conducted to evaluate the protective efficacy of the vaccine.
RESULTS: A total of 136 hepatitis A cases were reported during an outbreak that started in June, peaked in August and September, and ended after December of 2006. After a massive vaccination of school children in September, the number of cases declined significantly. No hepatitis A was detected in the 108 vaccinated individuals with close contacts of patients, whereas 4 cases of hepatitis A were found in the controls. The infection rate of hepatitis A was not significantly different in the individuals with close contacts of patients whether or not they received the vaccine (P = 0.122). No hepatitis A was detected in the 3365 students who received the vaccine, four cases of hepatitis A were found in the controls. The infection rate of students with or without vaccination was significantly different in the students who received the vaccine (0/3365 vs 4/2572, P = 0.035). The protective efficacy of the vaccine was 100%.
CONCLUSION: Inactivated hepatitis A vaccine demonstrates a good protective effect against an outbreak of hepatitis A.
PMCID: PMC2709045  PMID: 18461664
Hepatitis A; Outbreak; Inactivated hepatitis A vaccine; Emergency vaccination; Protective efficacy
11.  Predicting alcohol consumption during the month before and after beginning college 
We sought to determine predictors of drinking the month before and after beginning college, as well as changes in drinking between these two periods among adjudicated students. We conducted these analyses to inform individual and university-wide approaches to addressing underage drinking, particularly among the heaviest drinkers.
The sample consisted of 143 students entering college, adjudicated during their first semester, and interviewed during the same semester. The sample consisted of 43% women. Drinking data were collected through the Time-Line Follow-Back interview.
The average number of drinking days (DD) during the first month of college was 7.0 (SD = 4.7), the average number of drinks per drinking day (DDD) was 7.4 (SD = 3.4), and the average volume of standard drink units consumed during this month was 56.3 (SD = 51.2). Students had volunteered for a two-year college facilitation study, and had been invited to participate after receiving a citation for violating university alcohol policies. Analyses consisted of nine backward elimination regression analyses with nine variables entered as predictors (one was a control variable). Age of first intoxication was related to every dependent measure. Men had a higher August DDD, September DDD, and September volume than women. Roommate drinking level was associated with September DDD and September volume. Out-of-state students had a lower August volume than in-state students. High school rank was inversely related to September drinking days. SAT score, declared major status, and fraternity/sorority status were not related to drinking according to these multivariate analyses.
Results suggest that approaches to underage drinking for adjudicated students may need to be tailored according to age of first intoxication. Results also suggest the drinking level of the heaviest drinking roommate may moderate individual level interventions. Further, interventions applied to an entire dorm room may prove efficacious. Results also suggest that high school rank, rather than SAT scores, should be used as college entry criteria to yield a drier incoming class. Results may not generalize to non-adjudicated students.
PMCID: PMC2901345  PMID: 20550683
12.  527 Evaluation of the September Epidemic of Asthma Exacerbation in Children in Our Practice 
Know that the rate of asthma exacerbations are increased in September after summer vacation with the beginning of school year. Investigators have been studied this problem and it was supposed that the main cause could be the stress associated with school return what can worsen asthma symptoms. Beside this children returning to school after summer vacation are reexposed to respiratory viral infections, sensitizing allergens in the school enviroment, and can be connected with poor compliance in the medication in the summer period.
We stared to investigate that what could be the causative factors in children who suffered dyspnoe and other signs of asthmatic exacerbation from September 2008, could we present the increasing number of these patients in hospitalization rate, and could we confirm the changing compliance of the regular medication during the summer period? A short questionaire was constructed and was given the patients who were admitted to hospital (162) with asthma exacerbation symptoms. Then 45 patients were selected for a longer follow up to investigate their compliance in medication. We investigate from the database of our Hospital the asthmatic patient's admission rate from 2006.
We could present from 2006 the increasing number of patients admitted because of asthma exacerbation in September in every year. We could present the increased number of schoolage patient among all of the admitted patients in the fall season. We compared the genders which were similar. We found that the symptom of asthma was worse in the fall season. We confirmed the higher number of patients suffering from viral infections. But the changing rate among patient who stopped the medication during summer was low as 13%.
We could confirm the September epidemic of asthma exacerbation among our patients as well. Compare the international investigations the main cause of the September epidemic of asthma connecting with the beginning of the school year and the increasing number of viral infections at this period of the year. Fortunately our patient compliance was good but we have to continue our patients’ education from time to time.
PMCID: PMC3512688
13.  Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study 
BMJ : British Medical Journal  2001;322(7296):1203.
To evaluate the effects on suicidal behaviour of legislation limiting the size of packs of paracetamol and salicylates sold over the counter.
Before and after study.
UK population, with detailed monitoring of data from five liver units and seven general hospitals, between September 1996 and September 1999.
People who died by suicidal or accidental overdose with paracetamol or salicylates or who died of undetermined causes; patients admitted to liver units with hepatic paracetamol poisoning; patients presenting to general hospitals with self poisoning after taking paracetamol or salicylates.
Main outcome measures
Mortality from paracetamol or salicylate overdose; numbers of patients referred to liver units or listed for liver transplant; numbers of transplantations; numbers of overdoses and tablets taken; blood concentrations of the drugs; prothrombin times; sales to pharmacies and other outlets of paracetamol and salicylates.
Numbers of tablets per pack of paracetamol and salicylates decreased markedly in the year after the change in legislation on 16 September 1998. The annual number of deaths from paracetamol poisoning decreased by 21% (95% confidence interval 5% to 34%) and the number from salicylates decreased by 48% (11% to 70%). Liver transplant rates after paracetamol poisoning decreased by 66% (55% to 74%). The rate of non-fatal self poisoning with paracetamol in any form decreased by 11% (5% to 16%), mainly because of a 15% (8% to 21%) reduction in overdoses of paracetamol in non-compound form. The average number of tablets taken in paracetamol overdoses decreased by 7% (0% to 12%), and the proportion involving >32 tablets decreased by 17% (4% to 28%). The average number of tablets taken in salicylate overdoses did not decrease, but 34% fewer (2% to 56%) salicylate overdoses involved >32 tablets. After the legislation mean blood concentrations of salicylates after overdose decreased, as did prothrombin times; mean blood concentrations of paracetamol did not change.
Legislation restricting pack sizes of paracetamol and salicylates in the United Kingdom has had substantial beneficial effects on mortality and morbidity associated with self poisoning using these drugs.
What is already known on this topicParacetamol and salicylate overdoses are very common in the United Kingdom and are associated with high levels of mortality and morbidityInternational comparison shows that national mortality from paracetamol overdose may be related to the maximum number of tablets in individual preparationsLegislation to limit the size of packs of paracetamol and salicylates was introduced in the United Kingdom in September 1998What this study addsThe number of tablets in packets of paracetamol and salicylate preparations decreased markedly in the 12 months after the legislationThe number of deaths from self poisoning with paracetamol alone and with salicylates alone decreased after the legislationThere was also a decrease in the number of liver transplants and admissions to liver units with hepatic paracetamol poisoning and in the number of overdoses of paracetamol and salicylates in which large numbers of tablets were taken
PMCID: PMC31616  PMID: 11358770
14.  Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001. 
Environmental Health Perspectives  2002;110(7):703-714.
The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol plume impacting many workers, residents, and commuters during the first few days after 11 September 2001. Three bulk samples of the total settled dust and smoke were collected at weather-protected locations east of the WTC on 16 and 17 September 2001; these samples are representative of the generated material that settled immediately after the explosion and fire and the concurrent collapse of the two structures. We analyzed each sample, not differentiated by particle size, for inorganic and organic composition. In the inorganic analyses, we identified metals, radionuclides, ionic species, asbestos, and inorganic species. In the organic analyses, we identified polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, pesticides, phthalate esters, brominated diphenyl ethers, and other hydrocarbons. Each sample had a basic pH. Asbestos levels ranged from 0.8% to 3.0% of the mass, the PAHs were > 0.1% of the mass, and lead ranged from 101 to 625 microg/g. The content and distribution of material was indicative of a complex mixture of building debris and combustion products in the resulting plume. These three samples were composed primarily of construction materials, soot, paint (leaded and unleaded), and glass fibers (mineral wool and fiberglass). Levels of hydrocarbons indicated unburned or partially burned jet fuel, plastic, cellulose, and other materials that were ignited by the fire. In morphologic analyses we found that a majority of the mass was fibrous and composed of many types of fibers (e.g., mineral wool, fiberglass, asbestos, wood, paper, and cotton). The particles were separated into size classifications by gravimetric and aerodynamic methods. Material < 2.5 microm in aerodynamic diameter was 0.88-1.98% of the total mass. The largest mass concentrations were > 53 microm in diameter. The results obtained from these samples can be used to understand the contact and types of exposures to this unprecedented complex mixture experienced by the surviving residents, commuters, and rescue workers directly affected by the plume from 11 to 12 September and the evaluations of any acute or long-term health effects from resuspendable dust and smoke to the residents, commuters, and local workers, as well as from the materials released after 11 September until the fires were extinguished. Further, these results support the need to have the interior of residences, buildings, and their respective HVAC systems professionally cleaned to reduce long-term residential risks before rehabitation.
PMCID: PMC1240917  PMID: 12117648
15.  Task Shifting for Scale-up of HIV Care: Evaluation of Nurse-Centered Antiretroviral Treatment at Rural Health Centers in Rwanda 
PLoS Medicine  2009;6(10):e1000163.
Fabienne Shumbusho and colleagues evaluate a task-shifting model of nurse-centered antiretroviral treatment prescribing in rural primary health centers in Rwanda and find that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support.
The shortage of human resources for health, and in particular physicians, is one of the major barriers to achieve universal access to HIV care and treatment. In September 2005, a pilot program of nurse-centered antiretroviral treatment (ART) prescription was launched in three rural primary health centers in Rwanda. We retrospectively evaluated the feasibility and effectiveness of this task-shifting model using descriptive data.
Methods and Findings
Medical records of 1,076 patients enrolled in HIV care and treatment services from September 2005 to March 2008 were reviewed to assess: (i) compliance with national guidelines for ART eligibility and prescription, and patient monitoring and (ii) key outcomes, such as retention, body weight, and CD4 cell count change at 6, 12, 18, and 24 mo after ART initiation. Of these, no ineligible patients were started on ART and only one patient received an inappropriate ART prescription. Of the 435 patients who initiated ART, the vast majority had adherence and side effects assessed at each clinic visit (89% and 84%, respectively). By March 2008, 390 (90%) patients were alive on ART, 29 (7%) had died, one (<1%) was lost to follow-up, and none had stopped treatment. Patient retention was about 92% by 12 mo and 91% by 24 mo. Depending on initial stage of disease, mean CD4 cell count increased between 97 and 128 cells/µl in the first 6 mo after treatment initiation and between 79 and 129 cells/µl from 6 to 24 mo of treatment. Mean weight increased significantly in the first 6 mo, between 1.8 and 4.3 kg, with no significant increases from 6 to 24 mo.
Patient outcomes in our pilot program compared favorably with other ART cohorts in sub-Saharan Africa and with those from a recent evaluation of the national ART program in Rwanda. These findings suggest that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support.
Please see later in the article for the Editors' Summary
Editors' Summary
Infection with the human immunodeficiency virus (HIV) is a serious health problem in sub-Saharan Africa. The virus attacks white blood cells that protect against infection, most commonly a type of white blood cell called CD4. When a person has been infected with HIV for a long time, the number of CD4 cells they have goes down, resulting in acquired immune deficiency syndrome (AIDS), in which the person's immune system no longer functions effectively.
The World Health Organization (WHO) has divided the disease into four stages as it progresses, according to symptoms including weight loss and so-called opportunistic infections. These are known as clinical stage I, II, III, or IV but were revised and renamed 1, 2, 3, and 4 in September 2005. HIV infection and AIDS cannot be cured but they can be managed with antiretroviral treatment (ART). The WHO currently recommends that ART is begun when the CD4 count falls below 350.
Rwanda is a country situated in the central Africa with a population of around 9 million inhabitants; over 3% of the rural population and 7% of the urban population are infected with HIV. In 2007, the WHO estimated that 220,000 Rwandan children had lost one or both parents to AIDS.
Why Was This Study Done?
The WHO estimates that 9.7 million people with HIV in low- to middle-income countries need ART but at the end of 2007, only 30% of these, including in Rwanda, had access to treatment. In many low-income countries a major factor in this is a lack of doctors. Rwanda, for example, has one doctor per 50,000 inhabitants and one nurse per 3,900 inhabitants.
This situation has led the WHO to recommend “task shifting,” i.e., that the task of prescribing ART should be shifted from doctors to nurses so that more patients can be treated. This type of reorganization is well studied in high-income countries, but the researchers wanted to help develop a system for treating AIDS that would be effective and timely in a predominantly rural, low-income setting such as Rwanda.
What Did the Researchers Do and Find?
In conjunction with the Rwandan Ministry of Health, the researchers developed and piloted a task-shifting program, in which one nurse in each of three rural Rwandan primary health centers (PHCs) was trained to examine HIV patients and prescribe ART in simple cases. Nurses had to complete more than 50 consultations observed by the doctor before being permitted to consult patients independently. More complex cases were referred to a doctor. The authors developed standard checklists, instructions, and evaluation forms to guide nurses and the doctors who supervised them once a week.
The authors evaluated the pilot program by reviewing the records of 1,076 patients who enrolled on it between September 2005 and March 2008. They looked to see whether the nurses had followed guidelines and monitored the patients correctly. They also considered health outcomes for the patients, such as their death rate, their body weight, their CD4 cell count, and whether they maintained contact with caregivers.
They found that by March 2008, 451 patients had been eligible for ART. 435 received treatment and none of the patients were prescribed ART when they should not have been. Only one prescription did not follow national guidelines.
At every visit, nurses were supposed to assess whether patients were taking their drugs and to monitor side effects. They did this and maintained records correctly for the vast majority of the 435 patients who were prescribed ART. 390 patients (over 90%) of the 435 prescribed receiving ART continued to take it and maintain contact with the pilot PHC's program. 29 patients died. Only one was lost to follow up and the others transferred to another ART site. The majority gained weight in the first six months and their CD4 cell counts rose. Outcomes, including death rate, were similar to those treated on the (doctor-led) Rwandan national ART program and other sub-Saharan African national (doctor-led) programs.
What Do These Findings Mean?
The study suggests that nurses are able to prescribe ART safely and effectively in a rural sub-Saharan setting, given sufficient training, mentoring, and support. Nurse-led prescribing of ART could mean that timely, appropriate treatment reaches many more HIV patients. It would reduce the burden of HIV care for doctors, freeing their time for other duties, and the study is already being used by the Rwandan Ministry of Health as a basis for plans to adopt a task-shifting strategy for the national ART program.
The study does have some limitations. The pilot program was funded and designed as a health project to deliver ART in rural areas, rather than a research project to compare nurse-led and doctor-led ART programs. There was no group of equivalent patients treated by doctors rather than nurses for direct comparison, although the authors did compare outcomes with those achieved nationally for doctor-led ART. The most promising sites, nurses, and patients were selected for the pilot and careful monitoring may have been an additional motivation for the nurses and doctors taking part. Health professionals in a scaled-up program may not be as committed as those in the pilot, who were carefully monitored. In addition, the nature of the pilot, which lasted for under three years and recruited new patients throughout, meant that patients were followed up for relatively short periods.
The authors also warn that they did not consider in this study the changes task shifting will make to doctors' roles and the skills required of both doctors and nurses. They recommend that task shifting should be implemented as part of a wider investment in health systems, human resources, training, adapted medical records, tools, and protocols.
Additional Information
Please access these Web sites via the online version of this summary at
PLoS Medicine includes a page collecting together its recent articles on HIV infection and AIDS that includes research articles, perspectives, editorials, and policy forums provides news, views, and information about science, technology, and the developing world, including a section specific to HIV/AIDs
The World Health Organization (WHO) has published a downloadable booklet Task Shifting to Tackle Health Worker Shortages
The WHO offers information on HIV and AIDS (in Arabic, Chinese, English, French, Russian, and Spanish) as well as health information and fact sheets on individual countries, including on Rwanda
The UNAIDS/WHO working group on HIV/AIDS and Sexually Transmitted Infections (STI) Surveillance gathers and publishes data on the prevalence of HIV and AIDS in individual countries, including on Rwanda
AIDS.ORG provides information to help prevent HIV infections and to improve the lives of those affected by HIV and AIDS. Factsheets on many aspects of HIV and AIDS are available. It is the official online publisher of AIDS Treatment News
PMCID: PMC2752160  PMID: 19823569
16.  Tissue Adhesives for Simple Traumatic Lacerations 
Journal of Athletic Training  2008;43(2):222-224.
Reference/Citation: Farion K, Osmond MH, Hartling L, et al. Tissue adhesives for traumatic lacerations in children and adults. Cochrane Database Syst Rev. 2001(4);CD003326.
Clinical Question: What is the clinical evidence base for tissue adhesives in the management of simple traumatic lacerations?
Data Sources: Studies were identified by searches of the following databases: Cochrane Wounds Group Specialized Trials Register (September 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (CDROM 2003, issue 3), MEDLINE (1966 to September 2003, week 1), EMBASE (1988 to 2003, week 36), Web of Science Science Citation Index (1975 to September 13, 2003) and various clinical trials registers (September 2003). Investigators and product manufacturers were contacted to identify additional eligible studies. The search terms included wounds and injuries, laceration, face injury, nose injury, tissue adhesives, and acrylates.
Study Selection: Each study fulfilled the following criteria: (1) The study was a randomized controlled trial that compared tissue adhesives with standard wound closure (SWC) (sutures, staples, adhesive strips) or tissue adhesive with tissue adhesive. (2) The wounds were acute, linear lacerations less than 12 hours old, resulting from blunt or sharp trauma. (3) The wound length, width, and depth allowed for approximation of the edges with minimal tension after deep sutures were placed, if required. Studies were included with no language or publication status restriction, with participants of any age recruited in an emergency department, outpatient clinic, walk-in clinic, or other primary care setting. Studies were excluded if the wounds were stellate lacerations, puncture wounds, mammalian bites, infected, heavily contaminated or devitalized, crossing joints or mucocutaneous junctions, in hair-bearing areas, or in patients with keloid formation or chronic illness.
Data Extraction: The characteristics of the study and participants, interventions, outcome measures, and findings were extracted by one author and verified by a second using a standard form. The primary measure was cosmetic outcome. Secondary measures were pain with the procedure, time to complete the procedure, and complications (erythema, infection, discharge, need for delayed closure, and dehiscence). Studies were divided into 2 groups as follows: group 1, comparisons among tissue adhesives with SWC, and group 2, comparisons among different tissue adhesives. All eligible studies were assessed for methodologic quality independently by 2 investigators using the Jadad Scale, which evaluates randomization, double blinding, withdrawals, and dropouts and is scored on a 5-point (maximum) scale. The data from the tissue adhesive and SWC studies were pooled and analyzed with a random-effects model. The I 2 statistic was used to determine heterogeneity among the studies. χ 2 analysis was performed to compare participant age, wound location, and type of tissue adhesive among the studies. The data from the studies comparing tissue adhesives were pooled and analyzed using a fixed-effects model.
Main Results: The search criteria identified 39 eligible studies, of which 11 met the inclusion criteria. In 10 studies, a tissue adhesive was compared with SWC. Five groups used butylcyanoacrylate, and 5 used octylcyanoacrylate. For SWC, 6 groups used sutures, 2 used adhesive strips, and 2 used a combination of methods, although most used sutures. Six studies were limited to pediatric patients and 2 to adult patients; 2 included patients of any age. Wounds were limited to facial lacerations in 2 pediatric studies and 1 group with patients of any age. Lacerations requiring deep sutures were excluded in 4 studies. One group compared tissue adhesives (butylcyanoacrylate and octylcyanoacrylate) among pediatric patients with facial lacerations not requiring deep sutures. In the 11 included studies, authors of 9 randomized and evaluated 1 laceration per patient, whereas 2 groups included patients with more than 1 laceration. In 1 group, each laceration was independently randomized and evaluated, and the other group randomized the patient and assigned all lacerations to a treatment group (tissue adhesive with SWC or tissue adhesive with tissue adhesive). The sample sizes ranged between 60 and 163 lacerations, and all 11 studies were performed in emergency departments.
The primary measure in all included studies was cosmetic outcome. The majority of groups used the Cosmetic Visual Analogue Scale, the Wound Evaluation Score, or a combination of these measures. Three groups measured cosmetic outcome with nonvalidated scoring systems. Assessment time periods were grouped and reported at (1) 5 to 14 days, (2) 1 to 3 months, and (3) 9 to 12 months after wound closure. Secondary outcomes were pain (as noted on visual analogue scale) and time to complete the procedure (as mean number of minutes). The 11 studies scored from 1 to 3 on the Jadad Scale. Adequate allocation concealment was reported in only 1 group.
Examining cosmetic outcome, 8 groups (565 lacerations) used the Cosmetic Visual Analogue Scale to compare tissue adhesives and SWC. The authors reported no significant differences in scores at the time periods of 5 to 14 days, 1 to 3 months, and 9 to 12 months. A subgroup analysis showed a significant ( P = .005) superiority of butylcyanoacrylate over SWC at 1 to 3 months. Using the Wound Evaluation Score, 4 studies (364 lacerations) compared tissue adhesives with SWC. No significant differences in cosmetic scores were found at 5 to 14 days, 1 to 3 months, or 9 to 12 months. One group (83 lacerations) compared butylcyanoacrylate with octylcyanoacrylate and reported no significant differences in cosmetic scores using the Cosmetic Visual Analogue Scale at 1 to 3 months and the Wound Evaluation Score at 5 to 14 days and 1 to 3 months.
Examining secondary outcomes, 6 groups (570 lacerations) compared tissue adhesives with SWC using the visual analogue scale for pain. Scores reported by parents, patients, physicians, and nurses significantly favored tissue adhesives. In 6 studies (584 lacerations), tissue adhesives were significantly favored over SWC in time to complete the procedure. For complication outcomes, 8 groups (727 lacerations) demonstrated significantly fewer incidences of erythema and an increased risk of dehiscence with tissue adhesives compared with SWC. No significant differences were shown for infection, delayed closure, or discharge. Among 83 lacerations, 1 group compared butylcyanoacrylate with octylcyanoacrylate and reported no significant differences in combined patient-reported and parent-reported visual analogue pain scores, time to complete the procedure, dehiscence, or infection.
Conclusions: This review provides evidence that tissue adhesives are an option to SWC (sutures, staples, adhesive strips) for the management of simple traumatic lacerations. Overall, no significant differences were found in cosmetic scores at the reported assessment periods between tissue adhesives and SWC. At 1 to 3 months, a subgroup analysis significantly favored butylcyanoacrylate over SWC. Tissue adhesives significantly lowered the time to complete the procedure, levels of pain, and rate of erythema. However, the data revealed a significant increase in the rate of dehiscence with the use of tissue adhesives when compared with SWC. The low methodologic quality of the evidence should be considered in the interpretation of the findings.
PMCID: PMC2267332  PMID: 18345349
wound closure; tissue bonding; open wounds
17.  Acute Myocardial Infarction and Stress Cardiomyopathy following the Christchurch Earthquakes 
PLoS ONE  2013;8(7):e68504.
Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36am on 4 September 2010, magnitude 7.1 and at 12:51pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region's only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations.
Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others.
There was a significant increase in overall admissions (p<0.003), ST elevation myocardial infarction (p<0.016), and non cardiac chest pain (p<0.022) in the first 2 weeks following the early morning September earthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6–6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44–2.62). Statistical analysis showed this to be a significant difference between the earthquakes (p<0.05).
The early morning September earthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events.
PMCID: PMC3699519  PMID: 23844213
18.  Statins for age-related macular degeneration 
Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD.
To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD.
Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (, ( and the WHO International Clinical Trials Registry Platform (ICTRP) ( There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011.
Selection criteria
We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD.
Data collection and analysis
Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified.
Main results
Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing.
Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and retina status were unchanged during and after the treatment period for both groups.
Of the ongoing trial, the preliminary analyses of 42 participants who completed 12 months follow-up did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity, drusen score or visual function (effect estimates and confidence intervals were not available). We contacted the investigators and will update the review as data become available.
Authors' conclusions
Evidence from currently available RCTs was insufficient to conclude that statins have any role in preventing or delaying the onset or progression of AMD.
PMCID: PMC3804324  PMID: 22419318
19.  Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment 
In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning.
Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose.
There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million).
The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.
PMCID: PMC4243911  PMID: 24666324
acetylcysteine; adverse effects; paracetamol; poisoning; regulation
20.  Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment 
In September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning.
Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose.
There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million).
The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.
PMCID: PMC4243911  PMID: 24666324
acetylcysteine; adverse effects; paracetamol; poisoning; regulation
21.  The Results Database — Update and Key Issues 
The New England journal of medicine  2011;364(9):852-860.
The trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research.
We analyzed data that were publicly available between September 2009 and September 2010.
As of September 27, 2010, received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants.
CONCLUSIONS provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.
PMCID: PMC3066456  PMID: 21366476
22.  Real-World Efficiency of Pharmacogenetic Screening for Carbamazepine-Induced Severe Cutaneous Adverse Reactions 
PLoS ONE  2014;9(5):e96990.
We evaluated the cost and efficiency of routine HLA-B*15∶02 screening to prevent carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in Hong Kong.
Data were extracted from patients who commenced CBZ as the first-ever AED treatment or tested for HLA-B*15∶02 allele in three years before policy implementation (pre-policy: 16 September 2005 to 15 September 2008) and three years after (post-policy: 16 September 2008 to 15 September 2011). Using published unit costs, we estimated the cost of screening by comparing the costs to prevent and treat CBZ-SJS/TEN. We compared the number of person-tests needed and the cost to prevent resultant death with cancer screening programs.
The number of screening tests needed to prevent one case of CBZ-SJS/TEN was 442, and to prevent one resultant death was 1,474 to 8,840. The screening cost was $332 per person, of which 42% was attributed to an additional consultation to review result and prescribe appropriate medication. HLA-B*15∶02 screening expended $146,749 to prevent a case of CBZ-SJS/TEN, and $489,386– $2,934,986 to prevent a resultant death. The corresponding numbers of tests and costs for mammography and Pap smear to prevent death due to breast and cervical cancers were 7,150 and 7,000, and $614,900 and $273,000, respectively. Comparing to the SJS/TEN treatment cost, HLA-B*15∶02 screening would become cost saving if a point-of-care test of less than $37 was available.
HLA-B*15∶02 screening is as efficient as mammography and Pap smear in preventing death. Development of point-of-care testing will vastly improve efficiency.
PMCID: PMC4013087  PMID: 24806465
23.  Relationships among Body Condition, Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression during the Grazing Season in Mares 
PLoS ONE  2015;10(5):e0125968.
Obesity and insulin resistance have been shown to be risk factors for laminitis in horses. The objective of the study was to determine the effect of changes in body condition during the grazing season on insulin resistance and the expression of genes associated with obesity and insulin resistance in subcutaneous adipose tissue (SAT). Sixteen Finnhorse mares were grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland (NG) from the end of May to the beginning of September. Body measurements, intravenous glucose tolerance test (IVGTT), and neck and tailhead SAT gene expressions were measured in May and September. At the end of grazing, CG had higher median body condition score (7 vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05) and body weight (618 kg vs. 572 kg ± 10.21 (mean ± SEM); P=0.02), and larger waist circumference (P=0.03) than NG. Neck fat thickness was not different between treatments. However, tailhead fat thickness was smaller in CG compared to NG in May (P=0.04), but this difference disappeared in September. Greater basal and peak insulin concentrations, and faster glucose clearance rate (P=0.03) during IVGTT were observed in CG compared to NG in September. A greater decrease in plasma non-esterified fatty acids during IVGTT (P<0.05) was noticed in CG compared to NG after grazing. There was down-regulation of insulin receptor, retinol binding protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of adiponectin (ADIPOQ), adiponectin receptor 1 and stearoyl-CoA desaturase (SCD) gene expressions in SAT of both groups during the grazing season (P<0.05). Positive correlations were observed between ADIPOQ and its receptors and between SCD and ADIPOQ in SAT (P<0.01). In conclusion, grazing on CG had a moderate effect on responses during IVGTT, but did not trigger insulin resistance. Significant temporal differences in gene expression profiles were observed during the grazing season.
PMCID: PMC4418745  PMID: 25938677
24.  Violent attacks on Middle Easterners in the United States during the month following the September 11, 2001 terrorist attacks 
Injury Prevention  2003;9(2):187-189.
Methods: The LexisNexis database of newspaper reports were used to identify incidents of hate related violent acts against Middle Easterners or those perceived to be Middle Easterners in the US between September 1 and October 11, 2001. A total of 100 incidents of hate related violence were identified in the 2659 news articles that were reviewed.
Results: Of the 100 incidents of violent victimization that took place during the period September 1 to October 11, only one incident occurred before September 11. The 99 incidents that occurred after September 11 involved at least 128 victims and 171 perpetrators. Most violent victimizations occurred within 10 days of the attacks, involved male perpetrators and male victims, and occurred in convenience stores, on the streets, at gas stations, at schools/colleges, and at places of worship.
Discussion: Most violent victimizations occurred in the 10 days immediately following the terrorist attacks indicating that interventions that promote tolerance and understanding of diversity need to be implemented quickly in order to be effective. In addition, patrolling by police and Neighborhood Watch programs around convenience stores and gas stations may also be effective strategies for reducing hate related violent crimes.
PMCID: PMC1730950  PMID: 12810751
25.  Mediastinoscopy and bronchial carcinoma: experience with 600 mediastinoscopies. 
Thorax  1975;30(2):141-145.
Of 600 mediastinoscopies carried out from 1966 to 1973, 479 were performed to assess the operability of a pulmonary carcinoma. Of these, 206 (43%) were positive and 273 (57%) were negative. Of the 161 patients found positive during an initial period, 147 were refused operation; the remaining 14 were considered suitable candidates for operation, either because only one homolateral lymph node site was involved or because there was a concomitant osteoarthropathy. The tumour was irresectable in one of these 14 patients who died after 3-5 months; curative resection was possible in one and palliative resection in 12 patients. These 12 patients all died within a year. Of the 184 patients found negative during an initial period, 149 were treated by operation. The tumour proved irresectable in seven (5%), while curative resection was possible in 113 (76%) and palliative resection in 29 (19%) patients. Comparison with the period 1957-63, when in the same hospital resection was performed after a negative Daniels' (scalene node) biopsy, shows that the tumour was irresectable in 25 (20%) of the 124 patients with a negative biopsy, while curative resection was possible in 43 (35%) and palliative resection in 56 (45%) patients. During a second period, patients with a positive mediastinoscopy were in principle refused operation. Of 89 negative patients, 81 were treated by operation. No tumour was found to be irresectable; curative resection was possible in 63 (78%) and palliative resection in 18 (22%) patients. An operation for bronchial carcinoma was performed on 167 patients between September 1970 and September 1973 after a negative mediastinoscopy in 95, and without mediastinoscopy in 71 patients, either because of a peripheral tumour (70) or because of a tumour relapse after two years (1). The resection was palliative in 11% of the 71 cases, but in only one patient with a peripheral tumour could a mediastinoscopy have been positive. Finally, an operation was performed on one patient with a positive mediastinoscopy and a tumour relapse after six years. A survival study was made of the first 100 patients with pulmonary carcinoma, operated on between September 1970 and March 1972 and with a follow-up from a minumum of two years to a maximum of 3-5 years. The early mortality averaged 10% and was higher after pneumonectomy than after lobectomy. The late mortality was 16% after curative lobectomy, 38% after curative pneumonectomy, and 83% after palliative pneumonectomy. The survival after 2 to 3-5 years was 63%.
PMCID: PMC470258  PMID: 52198

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