Severe Lung Injury Associated With Use of e-Cigarette, or Vaping, Products-California, 2019.

Importance: Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market. Objective: To present clinical characteristics and vaping product exposures of patients with EVALI in California. Design, Setting, and Participants: Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019. Exposures: Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances. Main Outcomes and Measures: Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review. Results: Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products. Conclusions and Relevance: Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

Occupational coccidioidomycosis surveillance and recent outbreaks in California.

Workers in Coccidioides-endemic areas performing soil-disturbing work or exposed to windy and dusty conditions are at increased risk for coccidioidomycosis. Four occupational coccidioidomycosis outbreaks from 2007 to 2014 in California are described, involving construction workers in a number of excavation projects and an outdoor filming event involving cast and crew. These outbreaks highlight the importance of identifying industries and occupations at high risk for coccidioidomycosis, conducting targeted occupational health surveillance to assess the burden of illness, developing and implementing prevention strategies, and setting research priorities.

Knowledge, Attitudes, and Practices among Members of Households Actively Monitored or Quarantined to Prevent Transmission of Ebola Virus Disease - Margibi County, Liberia: February-March 2015.

BACKGROUND: In early 2015, a patient from a cluster of cases of Ebola Virus Disease (EVD) in Monrovia, Liberia traveled to a rural village in Margibi County, potentially exposing numerous persons. The patient died in the village and post-mortem testing confirmed Ebola Virus infection. Problem The Margibi County Health Team (CHT; Kakata, Margibi, Liberia) needed to prevent further transmission of EVD within and outside of the affected villages, and they needed to better understand the factors that support or impede compliance with measures to stop the spread of EVD. METHODS: In February-March 2015, the Margibi CHT instituted a 21-day quarantine and active monitoring for two villages where the patient had contact with numerous residents, and a 21-day active monitoring for five other villages where the patient had possible contact with an unknown number of persons. One contact developed EVD and quarantine was extended an additional 12 days in one village. In April 2015, the Margibi CHT conducted a household-based EVD knowledge, attitudes, and practices (KAP) survey of the seven villages. From April 24-29, 2015, interview teams approached every household in the seven villages and collected information on demographics, knowledge of EVD, attitudes about quarantine to prevent the spread of EVD, and their quarantine experiences and practices. Descriptive statistics were calculated. RESULTS: One hundred fifteen interviews were conducted, representing the majority of the households in the seven villages. Most (99%) correctly identified touching an infected person's body fluids and contact with the body of someone who has died from EVD as transmission routes. However, interviewees sometimes incorrectly identified mosquito bites (58%) and airborne spread (32%) as routes of EVD transmission, and 72% incorrectly identified the longest EVD incubation period as ≤seven days. Eight of 16 households in the two quarantined villages (50%) reported times when there was not enough water or food during quarantine. Nine of 16 (56%) reported that a household member had illnesses or injuries during quarantine; of these, all (100%) obtained care from a clinic, hospital, or Ebola treatment unit (ETU). CONCLUSION: Residents' knowledge of EVD transmission routes and incubation period were suboptimal. Public health authorities should consider assessing residents' understanding of Ebola transmission routes and effectively educate them to ensure correct understanding. Quarantined residents should be provided with sufficient food, water, and access to medical care. Wilken JA , Pordell P , Goode B , Jarteh R , Miller Z , Saygar BG Sr. , Maximore L , Borbor WM , Carmue M , Walker GW , Yeiah A . Knowledge, attitudes, and practices among members of households actively monitored or quarantined to prevent transmission of Ebola Virus Disease - Margibi County, Liberia: February-March 2015. Prehosp Disaster Med. 2017;32(6):673-678.

Dust Exposure and Coccidioidomycosis Prevention Among Solar Power Farm Construction Workers in California.

OBJECTIVES: To investigate if work activities, dust exposure, and protection measures were associated with a 2011 to 2014 coccidioidomycosis outbreak among workers constructing 2 solar farms in California. METHODS: In 2013, we mailed self-administered questionnaires to employees who were onsite at the solar farms where the outbreak occurred to identify cases of clinical coccidioidomycosis and compare with asymptomatic workers by using multivariate logistic regression. RESULTS: When we compared 89 workers with clinical coccidioidomycosis to 325 asymptomatic workers, frequently being in a dust cloud or storm (odds ratio [OR] = 5.93; 95% confidence interval [CI] = 3.18, 11.06) significantly increased the odds of clinical coccidioidomycosis, whereas frequently wetting soil before soil-disturbing activity (OR = 0.42; 95% CI = 0.24, 0.75) was protective. When we controlled for being in a dust cloud or storm, frequent soil disturbance significantly increased the odds of clinical coccidioidomycosis only among those who reported wearing a respirator infrequently (OR = 2.31; 95% CI = 1.27, 4.21). CONCLUSIONS: Utilization of personal and employer-driven safety practices and increased coccidioidomycosis awareness among construction workers should be considered during the planning of any construction work in coccidioidomycosis-endemic regions to prevent occupational infections and outbreaks.

Inhalational Chlorine Injuries at Public Aquatic Venues - California, 2008-2015.

In June 2015, personnel from California's Contra Costa Health Services Environmental Health and Hazardous Materials (hazmat) divisions were alerted to a possible chemical release at a swimming pool in an outdoor municipal water park. Approximately 50 bathers were in the pool when symptoms began; 34 (68%) experienced vomiting, coughing, or eye irritation. Among these persons, 17 (50%) were treated at the scene by Contra Costa's Emergency Medical Services (EMS) and released, and 17 (50%) were transported to local emergency departments; five patients also were evaluated later at an emergency department or by a primary medical provider. Environmental staff members determined that a chemical controller malfunction had allowed sodium hypochlorite and muriatic acid (hydrochloric acid) solutions to be injected into the main pool recirculation line while the recirculation pump was off; when the main recirculation pump was restarted, toxic chlorine gas (generated by the reaction of concentrated sodium hypochlorite and muriatic acid) was released into the pool. A review of 2008-2015 California pesticide exposure records identified eight additional such instances of toxic chlorine gas releases at public aquatic venues caused by equipment failure or human error that sickened 156 persons. Chemical exposures at public aquatic venues can be prevented by proper handling, storage, and monitoring of pool chemicals; appropriate equipment operation and maintenance; training of pool operators and staff members on pool chemical safety; and reporting of chemical exposures.

Physical, Mental, and Financial Impacts From Drought in Two California Counties, 2015.

OBJECTIVES: To evaluate health impacts of drought during the most severe drought in California's recorded history with a rapid assessment method. METHODS: We conducted Community Assessments for Public Health Emergency Response during October through November 2015 in Tulare County and Mariposa County to evaluate household water access, acute stressors, exacerbations of chronic diseases and behavioral health issues, and financial impacts. We evaluated pairwise associations by logistic regression with pooled data. RESULTS: By assessment area, households reported not having running water (3%-12%); impacts on finances (25%-39%), property (39%-54%), health (10%-20%), and peace of mind (33%-61%); worsening of a chronic disease (16%-46%); acute stress (8%-26%); and considering moving (14%-34%). Impacts on finances or property were each associated with impacts on health and peace of mind, and acute stress. CONCLUSIONS: Drought-impacted households might perceive physical and mental health effects and might experience financial or property impacts related to the drought. Public Health Implications. Local jurisdictions should consider implementing drought assistance programs, including behavioral health, and consider rapid assessments to inform public health action.

Thyroid Hormones and Timing of Pubertal Onset in a Longitudinal Cohort of Females, Northern California, 2006-11.

BACKGROUND: Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. METHODS: Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004-11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage ≥2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. RESULTS: At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per µg/dL respectively). CONCLUSIONS: Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche.

Occupational HIV Transmission Among Male Adult Film Performers - Multiple States, 2014.

In 2014, the California Department of Public Health was notified by a local health department of a diagnosis of acute human immunodeficiency virus (HIV) infection* and rectal gonorrhea in a male adult film industry performer, aged 25 years (patient A). Patient A had a 6-day history of rash, fever, and sore throat suggestive of acute retroviral syndrome at the time of examination. He was informed of his positive HIV and gonorrhea test results 6 days after his examination. Patient A had a negative HIV-1 RNA qualitative nucleic acid amplification test (NAAT)(†) 10 days before symptom onset. This investigation found that during the 22 days between the negative NAAT and being informed of his positive HIV test results, two different production companies directed patient A to have condomless sex with a total of 12 male performers. Patient A also provided contact information for five male non-work-related sexual partners during the month before and after his symptom onset. Patient A had additional partners during this time period for which no locating information was provided. Neither patient A nor any of his interviewed sexual partners reported taking HIV preexposure prophylaxis (PrEP). Contact tracing and phylogenetic analysis of HIV sequences amplified from pretreatment plasma revealed that a non-work-related partner likely infected patient A, and that patient A likely subsequently infected both a coworker during the second film production and a non-work-related partner during the interval between his negative test and receipt of his positive HIV results. Adult film performers and production companies, medical providers, and all persons at risk for HIV should be aware that testing alone is not sufficient to prevent HIV transmission. Condom use provides additional protection from HIV and sexually transmitted infections (STIs). Performers and all persons at risk for HIV infection in their professional and personal lives should discuss the use of PrEP with their medical providers.

Coccidioidomycosis among Workers Constructing Solar Power Farms, California, USA, 2011-2014.

Coccidioidomycosis is associated with soil-disruptive work in Coccidioides-endemic areas of the southwestern United States. Among 3,572 workers constructing 2 solar power-generating facilities in San Luis Obispo County, California, USA, we identified 44 patients with symptom onset during October 2011-April 2014 (attack rate 1.2 cases/100 workers). Of these 44 patients, 20 resided in California outside San Luis Obispo County and 10 resided in another state; 9 were hospitalized (median 3 days), 34 missed work (median 22 days), and 2 had disseminated disease. Of the 25 patients who frequently performed soil-disruptive work, 6 reported frequent use of respiratory protection. As solar farm construction in Coccidioides-endemic areas increases, additional workers will probably be exposed and infected unless awareness is emphasized and effective exposure reduction measures implemented, including limiting dust generation and providing respiratory protection. Medical providers, including those in non-Coccidioides-endemic areas, should suspect coccidioidomycosis in workers with compatible illness and report cases to their local health department.

Injuries and Traumatic Psychological Exposures Associated with the South Napa Earthquake - California, 2014.

On August 24, 2014, at 3:20 a.m., a magnitude 6.0 earthquake struck California, with its epicenter in Napa County (1). The earthquake was the largest to affect the San Francisco Bay area in 25 years and caused significant damage in Napa and Solano counties, including widespread power outages, five residential fires, and damage to roadways, waterlines, and 1,600 buildings (2). Two deaths resulted (2). On August 25, Napa County Public Health asked the California Department of Public Health (CDPH) for assistance in assessing postdisaster health effects, including earthquake-related injuries and effects on mental health. On September 23, Solano County Public Health requested similar assistance. A household-level Community Assessment for Public Health Emergency Response (CASPER) was conducted for these counties in two cities (Napa, 3 weeks after the earthquake, and Vallejo, 6 weeks after the earthquake). Among households reporting injuries, a substantial proportion (48% in Napa and 37% in western Vallejo) reported that the injuries occurred during the cleanup period, suggesting that increased messaging on safety precautions after a disaster might be needed. One fifth of respondents overall (27% in Napa and 9% in western Vallejo) reported one or more traumatic psychological exposures in their households. These findings were used by Napa County Mental Health to guide immediate-term mental health resource allocations and to conduct public training sessions and education campaigns to support persons with mental health risks following the earthquake. In addition, to promote community resilience and future earthquake preparedness, Napa County Public Health subsequently conducted community events on the earthquake anniversary and provided outreach workers with psychological first aid training.

Exposures and symptoms among workers after an offsite train derailment and vinyl chloride release.

OBJECTIVE: In 2012 in New Jersey, a train derailment resulted in the puncture of a tanker car carrying liquid vinyl chloride under pressure, and a resulting airborne vinyl chloride plume drifted onto the grounds of a nearby refinery. This report details the investigation of exposures and symptoms among refinery workers. DESIGN AND SETTING: The investigation team met with refinery workers to discuss their experience after the derailment and provided workers a self-administered survey to document symptoms and worker responses during the incident. Associations among categorical variables and experiencing symptoms were evaluated using Fisher's exact test. PARTICIPANTS: Twenty-six of 155 (17 percent) workers present at the refinery or driving on the access road the date the spill occurred completed the survey. MAIN OUTCOME MEASURE(S): Any self-reported symptom following exposure from the vinyl chloride release. RESULTS: Fifteen workers (58 percent) reported ≥1 symptom, most commonly headache (12, 46 percent). Three (12 percent) reported using respiratory protection. No differences in reporting symptoms were observed by location during the incident or by the building in which workers sheltered. Workers who moved from one shelter to another during the incident (ie, broke shelter) were more likely to report symptoms (Fisher's exact test, p=0.03); however, there are only limited data regarding vinyl chloride concentrations in shelters versus outside. CONCLUSIONS: Breaking shelter might result in greater exposures, and managers and health and safety officers of vulnerable facilities with limited physical access should consider developing robust shelter-in-place plans and alternate emergency egress plans. Workers should consider using respiratory protection if exiting a shelter is necessary during a chemical incident.

Assessing prevention measures and Sin Nombre hantavirus seroprevalence among workers at Yosemite National Park.

BACKGROUND: During 2012, a total of 10 overnight visitors to Yosemite National Park (Yosemite) became infected with a hantavirus (Sin Nombre virus [SNV]); three died. SNV infections have been identified among persons with occupational exposure to deer mice (Peromyscus maniculatus). METHODS: We assessed SNV infection prevalence, work and living environments, mice exposures, and SNV prevention training, knowledge, and practices among workers of two major employers at Yosemite during September-October, 2012 by voluntary blood testing and a questionnaire. RESULTS: One of 526 participants had evidence of previous SNV infection. Participants reported frequently observing rodent infestations at work and home and not always following prescribed safety practices for tasks, including infestation cleanup. CONCLUSION: Although participants had multiple exposures to deer mice, we did not find evidence of widespread SNV infections. Nevertheless, employees working around deer mice should receive appropriate training and consistently follow prevention policies for high-risk activities.

Coccidioidomycosis among cast and crew members at an outdoor television filming event--California, 2012.

In March 2013, the California Department of Public Health (CDPH) identified two Doctor's First Reports of Occupational Injury or Illness (DFRs) regarding Los Angeles County residents who had worked at the same jobsite in January 2012 and had been evaluated for possible work-associated coccidioidomycosis (valley fever). Occupational exposure to Coccidioides, the causative fungi, typically is associated with soil-disrupting activities. The physicians noted that both workers were cast or crew members filming a television series episode, and the site of possible exposure was an outdoor set in Ventura County, California. On the basis of their job titles, neither would have been expected to have been engaged in soil-disrupting activities. Los Angeles County Department of Public Health (LACDPH) conducted an outbreak investigation by using CDPH-provided occupational surveillance records, traditional infectious disease surveillance, and social media searches. This report describes the results of that investigation, which identified a total of five laboratory-confirmed and five probable cases linked to this filming event. The employer and site manager were interviewed. The site manager stated that they would no longer allow soil-disruptive work at the site and would incorporate information about the potential risk for Coccidioides exposure onsite into work contracts. Public health professionals, clinicians, and the television and film industry should be aware that employees working outdoors in areas where Coccidioides is endemic (e.g., central and southern California), even those not engaged in soil-disruptive work, might be at risk for coccidioidomycosis.

Shedding of soluble epidermal growth factor receptor (sEGFR) is mediated by a metalloprotease/fibronectin/integrin axis and inhibited by cetuximab.

Soluble epidermal growth factor receptor (sEGFR) is a circulating serum biomarker in cancer patients. Recent studies suggest that baseline serum sEGFR concentrations may predict responsiveness to EGFR-targeted therapy. Here, we demonstrate that sEGFR is generated through proteolytic cleavage of a cell surface precursor of an alternately spliced EGF receptor isoform and that sEGFR binds to EGF with high affinity. Proteolytic cleavage is stimulated by an anti-α5/ß1 integrin antibody and 4-aminophenylmercuric acetate, and inhibited by fibronectin. Two FDA-approved therapeutic anti-EGFR antibodies also inhibit shedding of sEGFR, thus implicating the cell surface precursor of sEGFR as a competing target for anti-EGFR antibodies in human tissues. These observations parallel trastuzumab regulation of HER2 shedding and have implications for patient stratification in future clinical trials of EGFR-targeted antibodies.

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study.

BACKGROUND: A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. METHODS: Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. RESULTS: Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. CONCLUSIONS: This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.

EGFR/HER-targeted therapeutics in ovarian cancer.

Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer. While several HER-targeted therapeutics are US FDA approved for the treatment of various malignancies, none have gained approval for the treatment of ovarian cancer. Here, we review the published literature on HER-targeted therapeutics for the treatment of ovarian cancer, including novel HER-targeted therapeutics in various stages of clinical development, as well as the challenges that have limited the use of these inhibitors in clinical settings.

The Ninth Annual American Association of cancer research international conference on frontiers in cancer prevention research.

UNLABELLED: The Ninth Annual AACR Frontiers in Cancer PREVENTION Research conference was held in Philadelphia in November 7-10, 2010. Its thematic focus was " PREVENTION: From Basic Science to Public Health Benefit." Telomere plasticity, the microenvironment, inflammation, transformation to the metastatic phenotype, and pathways to obesity were highlighted as important elements of carcinogenesis amenable to intervention. The integration of information from novel technologies related to physical biology, molecular and genetic profiles, and imaging along with behavioral and clinical parameters have advanced risk stratification and early detection. Cancer prevention represents a powerful testing ground for the development of individually tailored intervention and for increasing the efficiency of drug discovery. Advances in clinical trials relate to more efficient design strategies, have shown first-in-human targeting capabilities, and have developed powerful strategies to overcome accrual barriers. Tailored intervention strategies now show high efficacy on large cohorts across several cancer types. These successes are expected to increase.

Identification of immunoreactive regions of homology between soluble epidermal growth factor receptor and α5-integrin.

Proteins encoded by the epidermal growth factor receptor (EGFR/HER1/ERBB1) gene are being studied as diagnostic, prognostic, and theragnostic biomarkers for numerous human cancers. The clinical application of these tissue/tumor biomarkers has been limited, in part, by discordant results observed for epidermal growth factor receptor (EGFR) expression using different immunological reagents. Previous studies have used EGFR-directed antibodies that cannot distinguish between full-length and soluble EGFR (sEGFR) expression. We have generated and characterized an anti-sEGFR polyclonal antiserum directed against a 31-mer peptide (residues 604-634) located within the unique 78-amino acid carboxy-terminal sequence of sEGFR. Here, we use this antibody to demonstrate that sEGFR is coexpressed with EGFR in a number of carcinoma-derived cell lines. In addition, we show that a second protein of ~140 kDa (p140) also is detected by this antibody. Rigorous biochemical characterization identifies this second protein to be α5-integrin. We show that a 26-amino acid peptide in the calf domain of α5-integrin (residues 710-735) is 35% identical in sequence with a 31-mer carboxy-terminal sEGFR peptide and exhibits an approximately 5-fold lower affinity for anti-sEGFR than the homologous 31-mer sEGFR peptide does. We conclude that the carboxy terminus of sEGFR and the calf-1 domain of α5-integrin share a region of sequence identity, which results in their mutual immunological reactivity with anti-sEGFR. We also demonstrate that anti-sEGFR promotes three-dimensional tissue cohesion and compaction in vitro, further suggesting a functional link between sEGFR and α5-integrin and a role of the calf-1 domain in cell adhesion. These results have implications for the study of both EGFR and sEGFR as cancer biomarkers and also provide new insight into the mechanisms of interaction between cell surface EGFR isoforms and integrins in complex processes such as cell adhesion and survival signaling.