Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains, however, have developed the ability to cause disease of the gastrointestinal, urinary, or central nervous system in even the most robust human hosts. Diarrheagenic strains of E. coli can be divided into at least six different categories with corresponding distinct pathogenic schemes. Taken together, these organisms probably represent the most common cause of pediatric diarrhea worldwide. Several distinct clinical syndromes accompany infection with diarrheagenic E. coli categories, including traveler’s diarrhea (enterotoxigenic E. coli), hemorrhagic colitis and hemolytic-uremic syndrome (enterohemorrhagic E. coli), persistent diarrhea (enteroaggregative E. coli), and watery diarrhea of infants (enteropathogenic E. coli). This review discusses the current level of understanding of the pathogenesis of the diarrheagenic E. coli strains and describes how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens.

Diarrheagenic Escherichia coli

CA : A Cancer Journal for Clinicians

Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.

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CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

Thereisgrowinginterestinthepossiblehealththreatposedbyendocrine-disruptingchemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor , retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. (Endocrine Reviews 30: 293–342, 2009)

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Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

BACKGROUND
Overdose deaths involving opioid pain relievers (OPR), also known as opioid analgesics, have increased and now exceed deaths involving heroin and cocaine combined. This report describes the use and abuse of OPR by state.


METHODS
CDC analyzed rates of fatal OPR overdoses, nonmedical use, sales, and treatment admissions.


RESULTS
In 2008, drug overdoses in the United States caused 36,450 deaths. OPR were involved in 14,800 deaths (73.8%) of the 20,044 prescription drug overdose deaths. Death rates varied fivefold by state. States with lower death rates had lower rates of nonmedical use of OPR and OPR sales. During 1999--2008, overdose death rates, sales, and substance abuse treatment admissions related to OPR all increased substantially.


CONCLUSIONS
The epidemic of overdoses of OPR has continued to worsen. Wide variation among states in the nonmedical use of OPR and overdose rates cannot be explained by underlying demographic differences in state populations but is related to wide variations in OPR prescribing.


IMPLICATIONS FOR PUBLIC HEALTH PRACTICE
Health-care providers should only use OPRs in carefully screened and monitored patients when non-OPR treatments are insufficient to manage pain. Insurers and prescription drug monitoring programs can identify and take action to reduce both inappropriate and illegal prescribing. Third-party payers can limit reimbursement in ways that reduce inappropriate prescribing, discourage efforts to obtain OPR from multiple health-care providers, and improve clinical care. Changes in state laws that focus on the prescribing practices of health-care providers might reduce prescription drug abuse and overdoses while still allowing safe and effective pain treatment.

Vital Signs: Overdoses of Prescription Opioid Pain Relievers - United States, 1999-2008

ContextDaily consumption of 400 µg of folic acid before conception and
during early pregnancy dramatically reduces the occurrence of neural tube
defects (NTDs). Before food fortification, however, only an estimated 29%
of US reproductive-aged women were taking a supplement containing 400 µg
of folic acid daily. The US Food and Drug Administration authorized addition
of folic acid to enriched grain products in March 1996, with compliance mandatory
by January 1998.ObjectiveTo evaluate the impact of food fortification with folic acid on NTD
birth prevalence.Design, Setting, and PopulationNational study of birth certificate data for live births to women in
45 US states and Washington, DC, between January 1990 and December 1999.Main Outcome MeasureBirth certificate reports of spina bifida and anencephaly before fortification
(October 1995 through December 1996) compared with after mandatory fortification
(October 1998 through December 1999).ResultsThe birth prevalence of NTDs reported on birth certificates decreased
from 37.8 per 100 000 live births before fortification to 30.5 per 100 000
live births conceived after mandatory folic acid fortification, representing
a 19% decline (prevalence ratio [PR], 0.81; 95% confidence interval [CI],
0.75-0.87). During the same period, NTD birth prevalence declined from 53.4
per 100 000 to 46.5 per 100 000 (PR, 0.87; 95% CI, 0.64-1.18) for
women who received only third-trimester or no prenatal care.ConclusionsA 19% reduction in NTD birth prevalence occurred following folic acid
fortification of the US food supply. However, factors other than fortification
may have contributed to this decline.

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Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects

Context Use and abuse of prescription narcotic analgesics have increased dramatically in the United States since 1990. The effect of this pharmacoepidemic has been most pronounced in rural states, including West Virginia, which experienced the nation’s largest increase in drug overdose mortality rates during 1999-2004. Objective To evaluate the risk characteristics of persons dying of unintentional pharmaceutical overdose in West Virginia, the types of drugs involved, and the role of drug abuse in the deaths. Design, Setting, and Participants Population-based, observational study using data from medical examiner, prescription drug monitoring program, and opiate treatment program records. The study population was all state residents who died of unintentional pharmaceutical overdoses in West Virginia in 2006. Main Outcome Measures Rates and rate ratios for selected demographic variables. Prevalence of specific drugs among decedents and proportion that had been prescribed to decedents. Associations between demographics and substance abuse indicators and evidence of pharmaceutical diversion, defined as a death involving a prescription drug without a documented prescription and having received prescriptions for controlled substances from 5 or more clinicians during the year prior to death (ie, doctor shopping). Results Of 295 decedents, 198 (67.1%) were men and 271 (91.9%) were aged 18 through 54 years. Pharmaceutical diversion was associated with 186 (63.1%) deaths, while 63 (21.4%) were accompanied by evidence of doctor shopping. Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group. Having prescriptions for a controlled substance from 5 or morecliniciansintheyearpriortodeathwasmorecommonamongwomen(30[30.9%]) anddecedentsaged35through44years(23[30.7%])comparedwithmen(33[16.7%]) and other age groups (40 [18.2%]). Substance abuse indicators were identified in 279 decedents (94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicatedin234deaths(79.3%).Opioidanalgesicsweretakenby275decedents(93.2%), of whom only 122 (44.4%) had ever been prescribed these drugs. Conclusion The majority of overdose deaths in West Virginia in 2006 were associated with nonmedical use and diversion of pharmaceuticals, primarily opioid analgesics.

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Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities

Context Use and abuse of prescription narcotic analgesics have increased dramatically in the United States since 1990. The effect of this pharmacoepidemic has been most pronounced in rural states, including West Virginia, which experienced the nation's largest increase in drug overdose mortality rates during 1999-2004. Objective To evaluate the risk characteristics of persons dying of unintentional pharmaceutical overdose in West Virginia, the types of drugs involved, and the role of drug abuse in the deaths. Design, Setting, and Participants Population-based, observational study using data from medical examiner, prescription drug monitoring program, and opiate treatment program records. The study population was all state residents who died of unintentional pharmaceutical overdoses in West Virginia in 2006. Main Outcome Measures Rates and rate ratios for selected demographic variables. Prevalence of specific drugs among decedents and proportion that had been prescribed to decedents. Associations between demographics and substance abuse indicators and evidence of pharmaceutical diversion, defined as a death involving a prescription drug without a documented prescription and having received prescriptions for controlled substances from 5 or more clinicians during the year prior to death (ie, doctor shopping). Results Of 295 decedents, 198 (67.1 %) were men and 271 (91.9%) were aged 18 through 54 years. Pharmaceutical diversion was associated with 186 (63.1 %) deaths, while 63 (21.4%) were accompanied by evidence of doctor shopping. Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group. Having prescriptions for a controlled substance from 5 or more clinicians in the year prior to death was more common among women (30 [30.9%]) and decedents aged 35 through 44 years (23 [30.7%]) compared with men (33 [16.7%]) and other age groups (40 [18.2%]). Substance abuse indicators were identified in 279 decedents (94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicated in 234 deaths (79.3%). Opioid analgesics were taken by 275 decedents (93.2%), of whom only 122 (44.4%) had ever been prescribed these drugs. Conclusion The majority of overdose deaths in West Virginia in 2006 were associated with nonmedical use and diversion of pharmaceuticals, primarily opioid analgesics.

Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities. Commentary

Purpose
Since 1990, numerous jurisdictions in the United States (US) have reported increases in drug poisoning mortality. During the same time period, the use of opioid analgesics has increased markedly as part of more aggressive pain management. This study documented a dramatic increase in poisoning mortality rates and compared it to sales of opioid analgesics nationwide.

Methods
Trend analysis of drug poisoning deaths using underlying cause of death and multiple cause of death mortality data from the Centers for Disease Control and Prevention and opioid analgesic sales data from the US Drug Enforcement Administration.

Results
Unintentional drug poisoning mortality rates increased on average 5.3% per year from 1979 to 1990 and 18.1% per year from 1990 to 2002. The rapid increase during the 1990s reflects the rising number of deaths attributed to narcotics and unspecified drugs. Between 1999 and 2002, the number of opioid analgesic poisonings on death certificates increased 91.2%, while heroin and cocaine poisonings increased 12.4% and 22.8%, respectively. By 2002, opioid analgesic poisoning was listed in 5528 deaths—more than either heroin or cocaine. The increase in deaths generally matched the increase in sales for each type of opioid. The increase in deaths involving methadone tracked the increase in methadone used as an analgesic rather than methadone used in narcotics treatment programs.

Conclusions
A national epidemic of drug poisoning deaths began in the 1990s. Prescriptions for opioid analgesics also increased in this time frame and may have inadvertently contributed to the increases in drug poisoning deaths. Copyright © 2006 John Wiley & Sons, Ltd.

Leonard J. Paulozzi

Papers

Vital Signs: Overdoses of Prescription Opioid Pain Relievers - United States, 1999-2008

Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects

Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities

Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities. Commentary

Increasing deaths from opioid analgesics in the United States