BACKGROUND: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. METHODS: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS. RESULTS: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-β-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. CONCLUSION: Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis.

PURPOSE: Database linkage between cancer registries and clinical trial consortia has the potential to elucidate referral patterns of children and adolescents with newly diagnosed cancer, including enrollment into cancer clinical trials. This study's primary objective was to assess the feasibility of this linkage approach. METHODS: Patients younger than 20 years diagnosed with incident cancer during 2012-2017 in the Kentucky Cancer Registry (KCR) were linked with patients enrolled in a Children's Oncology Group (COG) study. Matched patients between databases were described by sex, age, race and ethnicity, geographical location when diagnosed, and cancer type. Logistic regression modeling identified factors associated with COG study enrollment. Timeliness of patient identification by KCR was reported through the Centers for Disease Control and Prevention's Early Case Capture (ECC) program. RESULTS: Of 1,357 patients reported to KCR, 47% were determined by matching to be enrolled in a COG study. Patients had greater odds of enrollment if they were age 0-4 years (v 15-19 years), reported from a COG-affiliated institution, and had renal cancer, neuroblastoma, or leukemia. Patients had lower odds of enrollment if Hispanic (v non-Hispanic White) or had epithelial (eg, thyroid, melanoma) cancer. Most (59%) patients were reported to KCR within 10 days of pathologic diagnosis. CONCLUSION: Linkage of clinical trial data with cancer registries is a feasible approach for tracking patient referral and clinical trial enrollment patterns. Adolescents had lower enrollment compared with younger age groups, independent of cancer type. Population-based early case capture could guide interventions designed to increase cancer clinical trial enrollment.

OBJECTIVES: To describe recent investigations of potential workplace cancer clusters. METHODS: We identified Health Hazard Evaluations (HHEs) of cancer concerns during 2001-2020. We described information about industry, requestors, cancer characteristics, investigative procedures, and determinations about the presence of a cluster (ie, presence of excess cases, unusual case distribution or exposure). RESULTS: Of 5754 HHEs, 174 included cancer concerns, comprising 1%-5% of HHEs per year. In 123 HHEs, the cancer cluster concerns involved different cancer primary sites. Investigation procedures varied but included record review (n=63, 36%) and site visits (n=22, 13%). Of 158 HHEs with a cluster determination by investigator(s), 151 (96%) were not considered cancer clusters. In seven HHEs, investigators found evidence of a cluster, but occupational exposure to a carcinogen was not identified. CONCLUSIONS: The proportion of HHEs on workplace cancer cluster concerns remained steady over time; most did not meet the definition of a cluster or uncover an occupational cause. Public health practitioners can use this information to provide updated context when addressing workplace cancer cluster concerns and as motivation to refine investigative approaches. More broadly, this review highlights an opportunity to identify best practices on how to apply community cluster investigation methods to the workplace.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: One author evaluated all titles and abstracts from the literature searches to determine their eligibility. Two authors independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons. Acceptability results favored the combination injectable in one study and the progestin-only in another.Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials. The NET-EN plus E(2)V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making. METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status. RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10-2.00]), largely driven by surveillance IMI cases. Aspergillus was the most common species cultured (33.5% prehurricane and 39.9% posthurricane). About one-quarter (25.8%) of IMI patients lacked classical IMI risk factors such as hematologic malignancy and transplantations. Overall, 45.1% of IMI patients received intensive care, and in-hospital all-cause mortality was 24.2%. CONCLUSIONS: IMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change.

BACKGROUND: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone. We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI). METHODS: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N=1255). We measured thirteen phthalate biomarkers and creatinine in 2-3 urine samples per participant collected over 3 years, when all participants were cancer-free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use. RESULTS: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT non-users, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT non-users and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%, 95% CI -2.81 - -0.78%) or mono-carboxynonyl phthalate (-1.84%, 95% CI -2.80 - -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change. DISCUSSION: Certain phthalate biomarkers are associated with greater percent decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.

We aimed to describe coronavirus disease 2019 (COVID-19) deaths among first responders early in the COVID-19 pandemic. We used media reports to gather timely information about COVID-19-related deaths among first responders during March 30-April 30, 2020, and evaluated the sensitivity of media scanning compared with traditional surveillance. We abstracted information about demographic characteristics, occupation, underlying conditions, and exposure source. Twelve of 19 US public health jurisdictions with data on reported deaths provided verification, and 7 jurisdictions reported whether additional deaths had occurred; we calculated the sensitivity of media scanning among these 7 jurisdictions. We identified 97 COVID-19-related first-responder deaths during the study period through media and jurisdiction reports. Participating jurisdictions reported 5 deaths not reported by the media. Sixty-six decedents worked in law enforcement, and 31 decedents worked in fire/emergency medical services. Media reports rarely noted underlying conditions. The media scan sensitivity was 88% (95% CI, 73%-96%) in the subset of 7 jurisdictions. Media reports demonstrated high sensitivity in documenting COVID-19-related deaths among first responders; however, information on risk factors was scarce. Routine collection of data on industry and occupation could improve understanding of COVID-19 morbidity and mortality among all workers.

PURPOSE OF REVIEW: To examine respiratory and skin diseases that occur among workers exposed to metalworking fluids (MWFs) used during machining processes. RECENT FINDINGS: Five cases of a severe and previously unrecognized lung disease characterized by B-cell bronchiolitis and alveolar ductitis with emphysema (BADE) were identified among workers at a machining facility that used MWFs, although MWF exposure could not be confirmed as the etiology. In the United Kingdom, MWF is now the predominant cause of occupational hypersensitivity pneumonitis (HP). Under continuous conditions associated with respiratory disease outbreaks, over a working lifetime of 45 years, workers exposed to MWF at 0.1 mg/m3 are estimated to have a 45.3% risk of acquiring HP or occupational asthma under outbreak conditions and a 3.0% risk assuming outbreak conditions exist in 5% of MWF environments. In addition to respiratory outcomes, skin diseases such as allergic and irritant contact dermatitis persist as frequent causes of occupational disease following MWF exposure. SUMMARY: Healthcare providers need to consider MWF exposure as a potential cause for work-related respiratory and skin diseases. Additional work is necessary to more definitively characterize any potential association between MWF exposures and BADE. Medical surveillance should be implemented for workers regularly exposed to MWF.

OBJECTIVES: Numerous states within the USA have legalized cannabis for medical or non-medical (adult/recreational) use. With the increased availability and use of cannabis, occupational and environmental exposures to secondhand cannabis smoke (SHCS) raise concerns over whether non-users may be at risk for a 'contact high', impaired neurocognitive function, harm from irritants and carcinogens in smoke, or potentially failing a cannabis screening test. The extent of health effects from potential occupational exposure to SHCS is unknown. This is a study of occupational exposures to SHCS among law enforcement officers (LEOs) providing security at outdoor concerts on a college campus in a state where adult use of cannabis is legal. METHODS: Investigators evaluated a convenience sample of LEOs' potential exposure to SHCS and symptoms experienced while providing security during two open-air stadium rock-n-roll concerts on consecutive days in July 2018. During each event, full-shift area and LEO personal air samples were collected for Delta9-tetrahydrocannabinol (Delta9-THC), the psychoactive component of cannabis. Urine (pre- and postevent; n = 58) and blood (postevent; n = 29) were also collected and analyzed for Delta9-THC and two of its metabolites [11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and 11-nor-hydroxy-delta-9-tetrahydrocannabinol (OH-THC)]. Urine samples were analyzed using ultrahigh performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry and results were compared with the Department of Transportation guidelines for urine screening for cannabis. Blood (postevent) samples were also collected and the plasma fraction was tested for Delta9-THC, THC-COOH, and OH-THC using high-performance liquid chromatography coupled with mass spectrometry. LEOs also completed a medical questionnaire asking about symptoms experienced during the concerts. RESULTS: Twenty-nine LEOs participated in the evaluation. Measurable amounts of Delta9-THC were found in area (concentrations ranged from non-detectable to 330 ng m-3) and personal air samples (53-480 ng m-3). Small amounts (<1.0 ng ml-1) of a Delta9-THC metabolite (THC-COOH) were found in the postevent urine of 34% of LEOs. Neither Delta9-THC nor its metabolites were detected in any blood sample. LEOs reported experiencing non-specific symptoms during the concerts, such as burning, itchy, or red eyes (31%); dry mouth (21%); headache (21%); and coughing (21%). CONCLUSIONS: Identification of Delta9-THC in the breathing zone for some LEOs indicates the potential for airborne exposure to the psychoactive component of cannabis. However, the magnitude of these exposures was small compared with those that would result in a dose of Delta9-THC associated with psychotropic effects. Similarly, THC-COOH was found in the postevent urine of some LEOs at concentrations that were orders of magnitude below active use cut-points used during a cannabis screening test (50 ng ml-1). Exposure to SHCS was not high enough to detect concentrations of THC, THC-COOH, to OH-THC in the blood, which could be due to differences between the limits of detection for the tests employed. The ocular and respiratory symptoms reported by LEOs may be related to irritants in SHCS. However, the health effects of SHCS remain unclear, and further research concerning occupational and environmental exposures is warranted.

Since 2004, the National Institute for Occupational Safety and Health (NIOSH) has received 10 cannabis-related health hazard evaluation (HHE) investigation requests from law enforcement agencies (n = 5), state-approved cannabis grow operations (n = 4), and a coroner's office (n = 1). Earlier requests concerned potential illicit drug exposures (including cannabis) during law enforcement activities and criminal investigations. Most recently HHE requests have involved state-approved grow operations with potential occupational exposures during commercial cannabis production for medicinal and non-medical (recreational) use. As of 2019, the United States Drug Enforcement Administration has banned cannabis as a Schedule I substance on the federal level. However, cannabis legalization at the state level has become more common in the USA. In two completed cannabis grow operation HHE investigations (two investigations are still ongoing as of 2019), potential dermal exposures were evaluated using two distinct surface wipe sample analytical methods. The first analyzed for delta-9-tetrahydrocannabinol (Delta9-THC) using a liquid chromatography and tandem mass spectrometry (LC-MS-MS) method with a limit of detection (LOD) of 4 nanograms (ng) per sample. A second method utilized high performance liquid chromatography with diode-array detection to analyze for four phytocannabinoids (Delta9-THC, Delta9-THC acid, cannabidiol, and cannabinol) with a LOD (2000 ng per sample) which, when comparing Delta9-THC limits, was orders of magnitude higher than the LC-MS-MS method. Surface wipe sampling results for both methods illustrated widespread contamination of all phytocannabinoids throughout the tested occupational environments, highlighting the need to consider THC form (Delta9-THC or Delta9-THC acid) as well as other biologically active phytocannabinoids in exposure assessments. In addition to potential cannabis-related dermal exposures, ergonomic stressors, and psychosocial issues, the studies found employees in cultivation, harvesting, and processing facilities could potentially be exposed to allergens and respiratory hazards through inhalation of organic dusts (including fungus, bacteria, and endotoxin) and volatile organic compounds (VOCs) such as diacetyl and 2,3-pentanedione. These hazards were most evident during the decarboxylation and grinding of dried cannabis material, where elevated job-specific concentrations of VOCs and endotoxin were generated. Additionally, utilization of contemporary gene sequencing methods in NIOSH HHEs provided a more comprehensive characterization of microbial communities sourced during cannabis cultivation and processing. Internal Transcribed Spacer region sequencing revealed over 200 fungal operational taxonomic units and breathing zone air samples were predominantly composed of Botrytis cinerea, a cannabis plant pathogen. B. cinerea, commonly known as gray mold within the industry, has been previously associated with hypersensitivity pneumonitis. This work elucidates new occupational hazards related to cannabis production and the evolving occupational safety and health landscape of an emerging industry, provides a summary of cannabis-related HHEs, and discusses critical lessons learned from these previous HHEs.

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine >/=10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

BACKGROUND: Cannabis has been legalized in some form for much of the United States. The National Institute for Occupational Safety and Health (NIOSH) received a health hazard evaluation request from a Minnesota cannabis facility and their union to undertake an evaluation. METHODS: NIOSH representatives visited the facility in August 2016 and April 2017. Surface wipe samples were collected for analysis of delta-9 tetrahydrocannabinol (Delta9-THC), delta-9 tetrahydrocannabinol acid (Delta9-THCA), cannabidiol, and cannabinol. Environmental air samples were collected for volatile organic compounds (VOCs), endotoxins (limulus amebocyte lysate assay), and fungal diversity (NIOSH two-stage BC251 bioaerosol sampler with internal transcribed spacer region sequencing analysis). RESULTS: Surface wipe samples identified Delta9-THC throughout the facility. Diacetyl and 2,3-pentanedione were measured in initial VOC screening and subsequent sampling during tasks where heat transference was greatest, though levels were well below the NIOSH recommended exposure limits. Endotoxin concentrations were highest during processing activities, while internal transcribed spacer region sequencing revealed that the Basidiomycota genus, Wallemia, had the highest relative abundance. CONCLUSIONS: To the authors' knowledge, this is the first published report of potential diacetyl and 2,3-pentanedione exposure in the cannabis industry, most notably during cannabis decarboxylation. Endotoxin exposure was elevated during grinding, indicating that this is a potentially high-risk task. The findings indicate that potential health hazards of significance are present during cannabis processing, and employers should be aware of potential exposures to VOCs, endotoxin, and fungi. Further research into the degree of respiratory and dermal hazards and resulting health effects in this industry is recommended.

BACKGROUND: Colorectal cancer (CRC) screening remains underutilized especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FIT) compared with usual care. METHODS: Patients aged 50-75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomized to outreach intervention with usual care versus usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at one year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided. RESULTS: 5,386 patients were randomized to the intervention group and 5,434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs. 37.4%, P < 0.001; difference 20.5%, 95% CI 18.6-22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT versus those who had not (71.9% vs. 35.7%, P < 0.001). There was evidence of effect modification of the intervention by race/ethnicity, marital status, language, and clinic. Outreach cost approximately $23/patient and $112/additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9,200/quality-adjusted life-year gained vs. usual care. CONCLUSION: Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remains to be determined.

In 2012, CDC’s National Institute for Occupational Safety and Health (NIOSH) became aware of the potential for occupational and take-home exposures to lead and cadmium in the electronics recycling industry (1) and contacted electronics industry stakeholders to discuss these exposures and provide information about NIOSH’s ability to investigate workplace hazards. NIOSH subsequently received requests for health hazard evaluations to estimate employee exposures and to assess the potential for take-home contamination from lead and cadmium at facilities A and B, in two states. Both facilities refurbished electronics for resale, removed electronic components for reuse and resale, and recycled electronics for waste management. Facility A employees received and inventoried electronics for either recycling or refurbishment and resale. Recycled materials were disassembled by hand or shredded using an industrial shredder. Employees at facility B performed similar job tasks as did those at facility A, but did not shred electronic parts.

Background: Human adenoviruses (HAdVs) are known causes of respiratory illness outbreaks in congregate settings, but cases and clusters are less well described from community settings in the United States. During December 2016-February 2017, the New Jersey Department of Health received reports of HAdV infections from 3 sources in 3 adjacent counties. We investigated to characterize the epidemiologic, laboratory, and clinical features of this HAdV outbreak. Methods: A case was defined as a New Jersey resident with acute respiratory illness during December 1, 2016-March 31, 2017 with laboratory identification of HAdV genome type 7d (HAdV-7d). Human adenovirus was detected by real-time and conventional polymerase chain reaction and molecular typed by partial hexon capsid protein gene sequencing. The HAdV genome type was identified by whole genome sequencing analysis. Available medical, public health, and surveillance records were reviewed. Results: We identified 12 cases, including 3 treatment facility patients, 7 college students, and 2 cases at a tertiary-care hospital. Four cases died; all had underlying comorbidities. Nine HAdV-7d whole genome sequences obtained from all 3 sites were nearly identical. Conclusions: Transmission of HAdV-7d occurred in community and congregate settings across 3 counties and resulted in severe morbidity and mortality in some cases with underlying comorbidities. Clinicians and local and state health departments should consider HAdV in patients with severe respiratory infection.

On February 3, 2017, a local health department notified the New Jersey Department of Health (NJDOH) of a severe respiratory illness outbreak, including two hospitalizations and one death, at a substance abuse treatment facility. During December 2016–January 2017, NJDOH surveillance for noninfluenza respiratory viruses identified multiple human adenovirus (HAdV) cases in the surrounding community. HAdVs can cause severe respiratory illness, and outbreaks of HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) have been associated with communal living facilities, including military barracks (1). A combined HAdV-4 and HadV-7 live oral vaccine is available but is currently limited to military use (2). NJDOH and the local health department investigated the outbreak in consultation with CDC to describe outbreak scope and provide infection control recommendations in this communal facility.

OBJECTIVES: All US states and territories have an Early Hearing Detection and Intervention (EHDI) program to facilitate early hearing evaluation and intervention for infants who are deaf or hard of hearing. To ensure efficient coordination of care, the state EHDI programs rely heavily on audiologists' prompt reporting of a newborn's hearing status. Several states have regulations requiring mandatory reporting of a newborn's hearing status. This is an important public health responsibility of pediatric audiologists. Reasons for failing to report vary. DESIGN: The Early Hearing Detection and Intervention-Pediatric Audiology Links to Services (EHDI) facility survey was used to inform reporting compliance of audiology facilities throughout the United States. The survey was disseminated via articles, newsletters, and call-to-action notices to audiologists. RESULTS: Among 1024 facilities surveyed, 88 (8.6%) reported that they did not report newborn's hearing findings to their state EHDI program. Not knowing how to report to the state EHDI program was the most frequently chosen reason (60%). However, among the 936 facilities that were compliant with the reporting requirements, 51 estimated that they reported less than two-third of all hearing evaluation results (5.4%). Some facilities did not report a normal-hearing result and some failed to report because they assumed another facility would report the hearing results. CONCLUSIONS: Survey results indicated that audiologists were compliant reporting hearing results to the state EHDI programs. However, there is room for improvement. Regular provider outreach and training by the state EHDI program is necessary to ensure those who are not reporting will comply and to clarify reporting requirements for those who are already compliant.

The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.

Drawing evidence from epidemiology and exposure assessment studies and recommendations from expert practice, we describe a process to guide health care providers helping their patients who present with symptoms that might be associated with living in damp housing. We present the procedures in the form of a guided 2-part interview. The first part has 5 questions that triage the patient toward a more detailed questionnaire that reflects features of housing conditions known to be reliably associated with exposures to mold and dampness contaminants. We chose the questions based on the conditions associated with moisture problems in homes across the United States and Canada. The goal is to facilitate the clinician's effort to help patients reduce exposure to environmental triggers that elicit symptoms to better manage their disease.

The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg-1 GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.

Dust mites are 8-legged arthropods that live in the house dust of homes located in regions where they are prevalent. They have been recognized as the major source of allergens in house dust since 1967. The most common species found in homes in temperate regions of the United States are Dermatophagoides farinae and Dermatophagoides pteronyssinus. In addition, others, such as Blomia tropicalis, can be found in homes in tropical and subtropical regions. | Dust mites feed on organic materials, including skin scales, fungi, yeasts, and bacteria. Because they are composed of approximately 75% water by weight, they maintain their water balance through uptake of water vapor when RH is at least approximately 65%. They are susceptible to water loss when humidity decreases below 65% and have decreased survival and reproduction with an RH below 50%. | Mites produce and excrete numerous allergens into the environment, including cysteine proteases such as Der p 1 and Der f 1, serine proteases including Der p 3, 6 and 9, and proteases that can activate protease-activated receptor-2, which are proinflammatory in humans through a non–IgE-dependent mechanism. Mites also produce glycosidases and carbohydrate-binding proteins and muscle, cytoskeleton, and calcium-binding proteins. There is cross-reactivity among various mite species and between mites and other related families, such as crustaceans and cockroaches.

BACKGROUND: Combination injectable contraceptives (CICs) provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of CICs. SEARCH METHODS: In January and February 2013, we searched for randomized controlled trials (RCTs) of combination injectable contraceptives. Databases include MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS. We searched for current trials in ClinicalTrials.gov and ICTRP.Earlier searches also included AIM and IMEMR. For the initial review, we also assessed the references listed in review articles and in the eligible trial reports. SELECTION CRITERIA: RCTs were eligible if they compared a combination injectable contraceptive with any other contraceptive method (e.g., a second CIC,a progestin-only injectable contraceptive, another hormonal contraceptive or a barrier method) or a placebo. We limited the review to marketed CICs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on contraceptive efficacy, bleeding patterns, continuation, and side effects. We calculated the Peto odds ratio or mean difference with 95% confidence interval for dichotomous or continuous outcome, respectively. Survival analysis estimates for method discontinuation were presented where available. MAIN RESULTS: Twelve trials met the inclusion criteria. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA)25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons.Acceptability results favored the CIC in one study and the progestin-only in another. Studies comparing two CICs found that NET-EN 50 mg plus E(2)V (5)mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials.The NET-EN plus E (2) V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward improving the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

During a pneumococcal disease outbreak in a pediatric psychiatric unit in a hospital in Rhode Island, USA, 6 (30%) of 20 patients and staff were colonized with Streptococcus pneumoniae serotype 15A, which is not included in pneumococcal vaccines. The outbreak subsided after implementation of antimicrobial drug prophylaxis and enhanced infection control measures.

BACKGROUND: Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. OBJECTIVES: The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. SEARCH STRATEGY: We searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). Searches were conducted from January to May 2011. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. SELECTION CRITERIA: All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. MAIN RESULTS: We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied. AUTHORS' CONCLUSIONS: Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non-hormonal group to control for other factors, including changes in weight over time.

The Centers for Disease Control and Prevention (CDC) estimate that 1.1 million people are living with HIV in the United States and approximately 56,000 new infections occur each year (CDC, 2008; Hall et al., 2008). By the end of 2006, an estimated 21% of people with HIV did not know that they were infected (calculated using extended back-calculation methods) (Campsmith et al., 2010). Many of those who do learn their serostatus are diagnosed in the late stages of the disease—approx-imately 38% of those who are diagnosed with HIV progress to AIDS within a year of their first positive HIV test. HIV transmission rates from persons who are aware of their seropositivity is approximately 3.3 compared to a rate of approximately 11.4 of those unaware of their seropositivity (Holtgrave, 2010). Furthermore, with high-quality care, a 25-year-old HIV-positive person can live an additional 39 years (Lohse, 2007). This information confirms the importance of routine HIV testing and early linkage to care for persons who test positive (CDC, 2009).

We agree with Dr. Grimes that epidemiologic research using administrative data can be problematic and is associated with possible pitfalls,1 and support his cautionary message about the careful use of these data in epidemiologic studies. However, we would like to point out that administrative claims data are ideal data for health services research and economic analyses. As is true of all data sources, administrative data are not a panacea for all research. The optimal data for a study should depend on the question being posed, and for some questions administrative data are the most appropriate choice. Many of the pitfalls that Dr. Grimes described can be avoided with careful analysis designs, transparency in the reporting of methods and results, and discussion of a study's limitations. | Administrative data are derived from insurers' billing systems and contain information about health plan enrollees' demographic characteristics, clinician profiles, healthcare services provided by providers who submit claims, and the cost of those services. These data are processed to create valid variables, are supported by a data clearinghouse, and made available for research. They are an invaluable resource for health services research studies monitoring access, utilization, quality of health services, and healthcare expenditures. Although Dr. Grimes discussed the use of Medicaid, Medicare, and HMO databases, he did not discuss the very large claims databases for services provided to other commercially-insured populations. These service provision data tend to be more complete, because services for most commercially-insured persons are typically provided on a fee-for-service basis which results in careful, complete filing of claims. This type of administrative data has steadily improved in completeness and accuracy in recent years by including more patient demographic information and laboratory testing data.2,3 Although medical records are thought to be the gold standard of healthcare service provision, analysis of administrative data along with medical record review can identify more sexual health services for adolescents than medical record review alone.4 In addition, administrative data have an important role in disease surveillance and outbreak detection in the United States.5 | The use of administrative data in health services and economic analyses can result in quality output that is essential for assessing the healthcare landscape, and the importance of these databases will grow in the upcoming years with the requirement to monitor both quality of services and spending for those services.

BACKGROUND: Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns. OBJECTIVES: To test the hypothesis that COCs containing ≤ 20 mug ethinyl estradiol (EE) perform similarly as those containing > 20 mug in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov, and ICTRP, and examined references of eligible trials. Initially, we wrote to oral contraceptive manufacturers to identify trials. SELECTION CRITERIA: English-language reports of randomized controlled trials were eligible that compare a COC containing ≤ 20 mug EE with a COC containing > 20 mug EE. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review. DATA COLLECTION AND ANALYSIS: One author evaluated all titles and abstracts from literature searches to determine whether they met the inclusion criteria. Two authors independently extracted data from studies identified for inclusion. We wrote to the researchers when additional information was needed. Data were entered and analyzed with RevMan. MAIN RESULTS: No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported. Compared to the higher-estrogen pills, several COCs containing 20 mug EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea or infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting). AUTHORS' CONCLUSIONS: While COCs containing 20 mug EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. Higher follow-up rates are essential for meaningful interpretation of results.