Carfentanil Outbreak - Florida, 2016-2017.

Increased prevalence of illicitly manufactured fentanyl and fentanyl analogs has contributed substantially to overdose deaths in the United States (1-3). On October 26, 2015, CDC issued a Health Advisory regarding rapid increases in deaths involving fentanyl. This CDC Health Advisory has been updated twice to address increases in fentanyl and fentanyl analog overdoses and their co-occurrence with nonopioids (4). Deaths involving carfentanil, an analog reportedly 10,000 times more potent than morphine and 100 times more potent than fentanyl, were first reported in Florida, Michigan, and Ohio in 2016 and described in an August 2016 CDC Health Advisory (1,5). Carfentanil is used to rapidly immobilize large animals in veterinary medicine and has no U.S. approved therapeutic use in humans. Carfentanil's street price per dose is likely lower than that of heroin. During 2016 and 2017, an outbreak of carfentanil-involved fatal overdoses in Florida emerged, and the Medical Examiner jurisdiction serving Sarasota, Manatee, and DeSoto counties (the Sarasota area) was the outbreak epicenter. This report describes toxicology profiles, sociodemographic information, and geographic distributions of carfentanil-involved fatal overdoses (carfentanil deaths) in the Sarasota area compared with those in the rest of Florida (i.e., all Florida counties excluding Sarasota area) from January 2016 to December 2017. The Sarasota area accounted for 19.0% of 1,181 statewide carfentanil deaths that occurred during this time and experienced a peak in carfentanil deaths preceding the larger Florida outbreak. The report of a single carfentanil death from August to December 2017 (compared with 73 reported deaths during the same period in 2016) appeared to mark the end of the outbreak in the area. The threat of such rapid, intense fatal overdose outbreaks highlights the need for accelerated reporting, reliable data sharing systems, and novel proactive surveillance to support targeted prevention and response efforts by public health and safety organizations (6).

Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015.† In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 - 10 States, July-December 2016.

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

Stressful and traumatic life events as disruptors to antiretroviral therapy adherence.

Stressful and traumatic life events (STLEs) are common among HIV-infected individuals and may affect health behaviors such as adherence to antiretroviral (ARV) therapy, with important implications for treatment outcomes. We examined the association between STLEs and ARV adherence among 289 US-based participants enrolled between 7/1/2010 and 9/1/2013 in a study of depression treatment for HIV-infected patients. Participants received monthly telephone calls to assess STLEs and pill count-based ARV adherence. Inverse probability of observation weighting was combined with multiple imputation to address missing data. Participants were mostly male (71%) and black (63%), with a median age of 45 years. Median monthly adherence was 96% (interquartile range (IQR): 85-100%). Participants experienced a mean of 2.48 STLEs (range: 0-14) in the previous month. The presence of ≥2 STLEs was associated with a mean change in adherence of -3.67% (95% confidence interval (CI): -7.12%, -0.21%) and decreased likelihood of achieving ≥95% adherence (risk ratio (95% CI) = 0.82 (0.71, 0.95)). For each additional STLE, the mean adherence change was -0.90% (95% CI: -1.79%, 0.00%). STLEs were associated with poorer ARV adherence, including decreased likelihood of adhering to ≥95% of ARV doses. This level of adherence has a critical role in regimen effectiveness and prevention of resistance.

Feasibility, safety, acceptability, and preliminary efficacy of measurement-based care depression treatment for HIV patients in Bamenda, Cameroon.

Depression affects 18-30 % of HIV-infected patients in Africa and is associated with greater stigma, lower antiretroviral adherence, and faster disease progression. However, the region's health system capacity to effectively identify and treat depression is limited. Task-shifting models may help address this large mental health treatment gap. Measurement-Based Care (MBC) is a task-shifting model in which a Depression Care Manager guides a non-psychiatric (e.g., HIV) provider in prescribing and managing antidepressant treatment. We adapted MBC for depressed HIV-infected patients in Cameroon and completed a pilot study to assess feasibility, safety, acceptability, and preliminary efficacy. We enrolled 55 participants; all started amitriptyline 25-50 mg daily at baseline. By 12 weeks, most remained at 50 mg daily (range 25-125 mg). Median (interquartile range) PHQ-9 depressive severity scores declined from 13 (12-16) (baseline) to 2 (0-3) (week 12); 87 % achieved depression remission (PHQ-9 <5) by 12 weeks. Intervention fidelity was high: HIV providers followed MBC recommendations at 96 % of encounters. Most divergences reflected a failure to increase dose when indicated. No serious and few bothersome side effects were reported. Most suicidality (prevalence 62 % at baseline; 8 % at 12 weeks) was either passive or low-risk. Participant satisfaction was high (100 %), and most participants (89 %) indicated willingness to pay for medications if MBC were implemented in routine care. The adapted MBC intervention demonstrated high feasibility, safety, acceptability, and preliminary efficacy in this uncontrolled pilot study. Further research should assess whether MBC could improve adherence and HIV outcomes in this setting.

Prevalence, characteristics and correlates of a positive-dementia screen in patients on antiretroviral therapy in Bamenda, Cameroon: a cross-sectional study.

BACKGROUND: In this study we assess the prevalence, characteristics as well as socio-demographic and clinical correlates of a positive screen for HIV-associated dementia in a group of patients on antiretroviral therapy (ART) in Bamenda, Cameroon. METHODS: In a cross-sectional study, a structured questionnaire was used to collect data on 400 patients attending the Bamenda Regional Hospital AIDS-treatment Centre. Patients were assessed for neurocognitive function using the International HIV Dementia Scale (IHDS) to assess finger-tapping (FT), alternating hand sequence (AHS) and a 4-word recall (4WR), each scored on a maximum of four. RESULTS: A total of 297 (74%) participants were females. The total IHDS score ranged from 6-12 with a mean of 9.02 and 85% of subjects screened positive for dementia (≤10 on IHDS). Participants performed worst in the AHS assessment with a mean of 2.25 (IQR: 2-3). In multivariable analyses, screening positive for dementia was significantly associated with having primary education or less (aOR: 8.33, 95%CI: 3.85, 16.67), and having HIV symptoms (aOR: 12.16, 95%CI: 3.08, 48.05). CONCLUSIONS: A very high proportion of patients on ART screened positive for dementia using the IHDS. This could potentially be an indication of a high prevalence of HIV-associated neurocognitive disorders in this population and or a poor performance of the IHDS in patients on ART. Future studies will need to assess the validity of the IHDS in this population of patients on ART and also evaluate long term outcomes in patients with positive dementia screens.

The depression treatment cascade in primary care: a public health perspective.

Major depressive disorder (MDD) is common and costly. Primary care remains a major access point for depression treatment, yet the successful clinical resolution of depression in primary care is uncommon. The clinical response to depression suffers from a "treatment cascade": the affected individual must access health care, be recognized clinically, initiate treatment, receive adequate treatment, and respond to treatment. Major gaps currently exist in primary care at each step along this treatment continuum. We estimate that 12.5% of primary care patients have had MDD in the past year; of those with MDD, 47% are recognized clinically, 24% receive any treatment, 9% receive adequate treatment, and 6% achieve remission. Simulations suggest that only by targeting multiple steps along the depression treatment continuum (e.g. routine screening combined with collaborative care models to support initiation and maintenance of evidence-based depression treatment) can overall remission rates for primary care patients be substantially improved.

Prevalence of and risk factors for chronic kidney disease in rural Nicaragua.

BACKGROUND: Mostly anecdotal reports describe a high prevalence of chronic kidney disease in northwestern Nicaragua, predominantly among younger men, resulting in substantial morbidity and mortality. The true prevalence, nature and aetiology of kidney disease in this region remain unknown. METHODS: We performed a population-based prevalence study in Quezalguaque, Nicaragua to assess the frequency of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), and compared the prevalence of reduced eGFR in Quezalguaque with the USA using the NHANES 1999-2006 data. We also conducted an embedded case-control study in a subset of participants to assess kidney disease risk factors. RESULTS: From 1882 eligible households, 771 individuals from 300 households participated in the prevalence study, 98 (13%) of whom had reduced eGFR. Reduced eGFR was more common among older participants, men and participants living at lower altitudes. Among 18-29-year-old participants, 2.6% had reduced eGFR, and among 30-41-year-old participants, 7.4% had reduced eGFR; this compares with 0.2% and 0.8%, respectively, in NHANES. No individuals in these age groups were diabetic. Among cases, only 27% had dipstick proteinuria of 1+ or greater, compared with 7% of controls. Haematuria did not significantly differ between cases and controls (24% versus 18%). In age- and sex-adjusted models, hypertension and residence at lower altitude were independently associated with reduced eGFR, while occupational history was not associated with reduced eGFR. CONCLUSIONS: Kidney disease appears common in residents of Quezalguaque, Nicaragua, particularly in younger men, with features most consistent with tubulointerstitial disease. Further research is needed to elucidate the causes of kidney disease in this region.

A reengineered hospital discharge program to decrease rehospitalization: a randomized trial.

BACKGROUND: Emergency department visits and rehospitalization are common after hospital discharge. OBJECTIVE: To test the effects of an intervention designed to minimize hospital utilization after discharge. DESIGN: Randomized trial using block randomization of 6 and 8. Randomly arranged index cards were placed in opaque envelopes labeled consecutively with study numbers, and participants were assigned a study group by revealing the index card. SETTING: General medical service at an urban, academic, safety-net hospital. PATIENTS: 749 English-speaking hospitalized adults (mean age, 49.9 years). INTERVENTION: A nurse discharge advocate worked with patients during their hospital stay to arrange follow-up appointments, confirm medication reconciliation, and conduct patient education with an individualized instruction booklet that was sent to their primary care provider. A clinical pharmacist called patients 2 to 4 days after discharge to reinforce the discharge plan and review medications. Participants and providers were not blinded to treatment assignment. MEASUREMENTS: Primary outcomes were emergency department visits and hospitalizations within 30 days of discharge. Secondary outcomes were self-reported preparedness for discharge and frequency of primary care providers' follow-up within 30 days of discharge. Research staff doing follow-up were blinded to study group assignment. RESULTS: Participants in the intervention group (n = 370) had a lower rate of hospital utilization than those receiving usual care (n = 368) (0.314 vs. 0.451 visit per person per month; incidence rate ratio, 0.695 [95% CI, 0.515 to 0.937]; P = 0.009). The intervention was most effective among participants with hospital utilization in the 6 months before index admission (P = 0.014). Adverse events were not assessed; these data were collected but are still being analyzed. LIMITATION: This was a single-center study in which not all potentially eligible patients could be enrolled, and outcome assessment sometimes relied on participant report. CONCLUSION: A package of discharge services reduced hospital utilization within 30 days of discharge. FUNDING: Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute, National Institutes of Health.

Prevalence and correlates of probable depression diagnosis and suicidal ideation among patients receiving HIV care in Lilongwe, Malawi.

BACKGROUND: Depression and suicide ideation among people living with HIV (PLHIV) can threaten the success of HIV care and treatment programs, particularly within high HIV prevalence settings. We describe the prevalence and correlates associated with depression and suicidal ideation among PLHIV receiving HIV care in Lilongwe, Malawi. METHODS: From July to September 2013, 206 HIV clinic patients, who were ≥18 years of age and either pre-antiretroviral therapy (ART) or established on ART for ≥6 months prior to study, participated in a survey to assess the prevalence of a likely depressive disorder and suicidal ideation using the Patient Health Questionnaire-9. We explored factors associated with depression using bivariable linear regression and suicidal ideation using bivariable log-binomial regression. RESULTS: The prevalence of a likely depressive disorder and suicidal ideation was 12% (95% CI: 8%, 17%) and 16% (95% CI: 11%, 21%), respectively. Pre-ART patients (ß=1.17, 95% CI: 0.03, 2.30, p-value=0.04) and those with problematic alcohol use (ß=0.49, 95% CI: 0.07, 0.92, p-value=0.02) were associated with a higher depression severity. Suicidal ideation was relatively common (8%, 95% CI: 5%, 13%) among those without a likely depressive disorder and significantly correlated with having no primary, secondary, or tertiary education (ß=-1.52, 95% CI: -2.46, -0.59, p-value<0.01). CONCLUSIONS: Interventions that enhance identification and management of depressive disorders and suicidal ideation should be integrated within HIV care clinics in Malawi.

Ongoing life stressors and suicidal ideation among HIV-infected adults with depression.

BACKGROUND: Suicidal ideation is the most proximal risk factor for suicide and can indicate extreme psychological distress; identification of its predictors is important for possible intervention. Depression and stressful or traumatic life events (STLEs), which are more common among HIV-infected individuals than the general population, may serve as triggers for suicidal thoughts. METHODS: A randomized controlled trial testing the effect of evidence-based decision support for depression treatment on antiretroviral adherence (the SLAM DUNC study) included monthly assessments of incident STLEs, and quarterly assessments of suicidal ideation (SI). We examined the association between STLEs and SI during up to one year of follow-up among 289 Southeastern US-based participants active in the study between 7/1/2011 and 4/1/2014, accounting for time-varying confounding by depressive severity with the use of marginal structural models. RESULTS: Participants were mostly male (70%) and black (62%), with a median age of 45 years, and experienced a mean of 2.36 total STLEs (range: 0-12) and 0.48 severe STLEs (range: 0-3) per month. Every additional STLE was associated with an increase in SI prevalence of 7% (prevalence ratio (PR) (95% confidence interval (CI)): 1.07 (1.00, 1.14)), and every additional severe STLE with an increase in SI prevalence of 19% (RR (95% CI): 1.19 (1.00, 1.42)). LIMITATIONS: There was a substantial amount of missing data and the exposures and outcomes were obtained via self-report; methods were tailored to address these potential limitations. CONCLUSIONS: STLEs were associated with increased SI prevalence, which is an important risk factor for suicide attempts and completions.

Changes in HIV Outcomes Following Depression Care in a Resource-Limited Setting: Results from a Pilot Study in Bamenda, Cameroon.

BACKGROUND: Little is known about how improved depression care affects HIV-related outcomes in Africa. In a sample of depressed HIV patients in a low income, sub-Saharan country, we explored how implementing measurement-based antidepressant care (MBC) affected HIV outcomes over 4 months of antidepressant treatment. METHODS: As part of a project adapting MBC for use in Cameroon, we enrolled 41 depressed HIV patients on antiretroviral therapy in a pilot study in which a depression care manager (DCM) provided an outpatient HIV clinician with evidence-based decision support for antidepressant treatment. Acute depression management was provided for the first 12 weeks, with DCM contact every 2 weeks and HIV clinician appointments every 4 weeks. We measured HIV clinical and psychiatric outcomes at 4 months. RESULTS: Participants were moderately depressed at baseline (mean Patient Health Questionnaire [PHQ] score = 14.4, range 13.1, 15.6). All HIV clinical outcomes improved by four month follow-up: mean (range) CD4 count improved from 436 (2, 860) to 452 (132, 876), mean (range) log-viral load decreased from 4.02 (3.86, 4.17) to 3.15 (2.81, 3.49), the proportion with virologic suppression improved from 0% to 18%, mean (range) HIV symptoms decreased from 6.4 (5.5, 7.3) to 3.1 (2.5, 3.7), the proportion reporting good or excellent health improved from 18% to 70%, and the proportion reporting any missed ARV doses in the past month decreased from 73% to 55%. Concurrently, psychiatric measures improved. The mean (range) PHQ score decreased from 14.4 (13.1, 15.6) to 1.6 (0.8, 2.4) and 90% achieved depression remission, while mean maladaptive coping style scores decreased and mean adaptive coping scores and self-efficacy scores improved. CONCLUSION: In this pilot study of an evidence-based depression treatment intervention for HIV-infected patients in Cameroon, a number of HIV behavioral and non-behavioral health outcomes improved over 4 months of effective depression treatment. These data are consistent with the hypothesis that better depression care can lead to improved HIV outcomes.

Providers' attitudes towards treating depression and self-reported depression treatment practices in HIV outpatient care.

Depression is highly prevalent among HIV-infected patients, yet little is known about the quality of HIV providers' depression treatment practices. We assessed depression treatment practices of 72 HIV providers at three academic medical centers in 2010-2011 with semi-structured interviews. Responses were compared to national depression treatment guidelines. Most providers were confident that their role included treating depression. Providers were more confident prescribing a first antidepressant than switching treatments. Only 31% reported routinely assessing all patients for depression, 13% reported following up with patients within 2 weeks of starting an antidepressant, and 36% reported systematically assessing treatment response and tolerability in adjusting treatment. Over half of providers reported not being comfortable using the full FDA-approved dosing range for antidepressants. Systematic screening for depression and best-practices depression management were uncommon. Opportunities to increase HIV clinicians' comfort and confidence in treating depression, including receiving treatment support from clinic staff, are discussed.

Validity of an interviewer-administered patient health questionnaire-9 to screen for depression in HIV-infected patients in Cameroon.

BACKGROUND: In high-income countries, depression is prevalent in HIV patients and is associated with lower medication adherence and clinical outcomes. Emerging evidence from low-income countries supports similar relationships. Yet little research has validated rapid depression screening tools integrated into routine HIV clinical care. METHODS: Using qualitative methods, we adapted the Patient Health Questionnaire-9 (PHQ-9) depression screening instrument for use with Cameroonian patients. We then conducted a cross-sectional validity study comparing an interviewer-administered PHQ-9 to the reference standard Composite International Diagnostic Interview in 400 patients on antiretroviral therapy attending a regional HIV treatment center in Bamenda, Cameroon. RESULTS: The prevalence of major depressive disorder (MDD) in the past month was 3% (n=11 cases). Using a standard cutoff score of ≥10 as a positive depression screen, the PHQ-9 had estimated sensitivity of 27% (95% confidence interval: 6-61%) and specificity of 94% (91-96%), corresponding to positive and negative likelihood ratios of 4.5 and 0.8. There was little evidence of variation in specificity by gender, number of HIV symptoms, or result of a dementia screen. LIMITATIONS: The low prevalence of MDD yielded very imprecise sensitivity estimates. Although the PHQ-9 was developed as a self-administered tool, we assessed an interviewer-administered version due to the literacy level of the target population. CONCLUSION: The PHQ-9 demonstrated high specificity but apparently low sensitivity for detecting MDD in this sample of HIV patients in Cameroon. Formative work to define the performance of proven screening tools in new settings remains important as research on mental health expands in low-income countries.

Post-discharge hospital utilization among adult medical inpatients with depressive symptoms.

BACKGROUND: Little evidence exists to determine whether depression predicts hospital utilization following discharge among adult inpatients on a general medical service. OBJECTIVE: We aimed to determine whether a positive depression screen during hospitalization is significantly associated with an increased rate of returning for hospital services. DESIGN: A secondary analysis was performed using data from 738 English-speaking, hospitalized adults from the Project RED randomized controlled trial (clinicaltrials.gov Identifier: NCT00252057) conducted at an urban academic safety-net hospital. MEASUREMENTS: We used the nine-item Patient Health Questionnaire (PHQ-9) depression screening tool to identify patients with depressive symptoms. The primary endpoint was hospital utilization, defined as the number of emergency department (ED) visits plus readmissions within 30 days of discharge. Poisson regression was used to control for confounding variables. RESULTS: Of the 738 subjects included in the analysis, 238 (32%) screened positive for depressive symptoms. The unadjusted hospital utilization within 30 days of discharge was 56 utilizations per 100 depressed patients compared with 30 utilizations per 100 non-depressed patients, incident rate ratio (IRR) (confidence interval [CI]), 1.90 (1.51-2.40). After controlling for potential confounders, a higher rate of post-discharge hospital utilization was observed in patients with depressive symptoms compared to patients without depressive symptoms (IRR [CI], 1.73 [1.27-2.36]). CONCLUSIONS: A positive screen for depressive symptoms during an inpatient hospital stay is associated with an increased rate of readmission within 30 days of discharge in an urban, academic, safety-net hospital population.