Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

A qualitative analysis of rural syringe service program fidelity in Appalachian Kentucky: Staff and participant perspectives.

PURPOSE: As drug-related epidemics have expanded from cities to rural areas, syringe service programs (SSPs) and other harm reduction programs have been slow to follow. The recent implementation of SSPs in rural areas demands attention to program fidelity based on core components of SSP success. METHODS: Semistructured interviews conducted with clients and staff at 5 SSPs in 5 counties within 2 Central Appalachian health districts. Interviews covered fidelity of SSP implementation to 6 core components: (1) meet needs for harm reduction supplies; (2) education and counseling for sexual, injection, and overdose risks; (3) cooperation between SSPs and local law enforcement; (4) provide other health and social services; (5) ensure low threshold access to services; and (6) promote dignity, the impact of poor fidelity on vulnerability to drug-related harms, and the risk environment's influence on program fidelity. We applied thematic methods to analyze the data. FINDINGS: Rural SSPs were mostly faithful to the 6 core components. Deviations from core components can be attributed to certain characteristics of the local rural risk environment outlined in the risk environment model, including geographic remoteness, lack of resources and underdeveloped infrastructure, and stigma against people who inject drugs (PWID) CONCLUSIONS: As drug-related epidemics continue to expand outside cities, scaling up SSPs to serve rural PWID is essential. Future research should explore whether the risk environment features identified also influence SSP fidelity in other rural areas and develop and test strategies to strengthen core components in these vulnerable areas.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Geographic distribution of risk ("Hotspots") for HIV, HCV, and drug overdose among persons who use drugs in New York City: the importance of local history.

AIMS: To identify geographic "hotspots" for potential transmission of HIV and HCV and for drug overdose among persons who use heroin and cocaine in New York City and to examine historical continuities in problem drug use hotspots in the city. METHODS: A total of 2714 study participants were recruited among persons entering Beth Israel substance use treatment programs. A structured questionnaire was administered and blood samples for HIV and HCV testing were collected. Hotspots for potential virus transmission were defined as ZIP codes with 10+ participants, 2+ persons infected with the virus and engaging in transmission behavior, and 2+ persons not infected and engaging in acquisition behavior. ZIP codes with 3+ persons with previous overdoses were considered potential hotspots for future overdoses. RESULTS: Participants resided in 166/178 (93%) of the ZIP codes in New York City. Injecting drug use was reported in 150/178 (84%) of the ZIP codes. No zip codes were identified for injecting-related HIV transmission, 5 zip codes were identified for sexual HIV transmission, 3 for HCV transmission, and 8 for drug overdose. Many of the ZIP code potential hotspots were in neighborhoods long associated with drug use: Lower Eastside and Harlem in Manhattan, the South Bronx, and Central Brooklyn. DISCUSSION: Heroin and cocaine use requiring treatment were reported from almost all ZIP codes in New York City, indicating needs for widely dispersed harm reduction services. Identified hotspots should be targeted for reducing sexual transmission of HIV, transmission of HCV, and drug overdoses. Some of the hotspots have persisted as problem drug use areas for 40 to over 100 years. Monitoring of drug use patterns in historical hotspot neighborhoods may permit early identification of and response to emerging drug use-related health problems. Persistent historical hotspots for problem drug use present a complex problem for implementing harm reduction services that deserve additional research.

Hepatitis C virus prevalence and estimated incidence among new injectors during the opioid epidemic in New York City, 2000-2017: Protective effects of non-injecting drug use.

OBJECTIVE: Assess hepatitis C virus (HCV) prevalence and incidence among person who began injecting drugs during the opioid epidemic in New York City (NYC) and identify possible new directions for reducing HCV infection among persons who inject drugs. METHODS: 846 persons who began injecting drugs between 2000 and 2017 were recruited from persons entering Mount Sinai Beth Israel substance use treatment programs. A structured interview was administered and HCV antibody testing conducted. Protective effects of non-injecting drug use were examined among persons who "reversed transitioned" to non-injecting drug use and persons who used non-injected heroin in addition to injecting. RESULTS: Participants were 79% male, 41% White, 15% African-American, 40% Latinx, with a mean age of 35. Of those who began injecting in 2000 or later, 97 persons (11%) "reverse transitioned" back to non-injecting drug use. Reverse transitioning was strongly associated with lower HCV seroprevalence (30% versus 47% among those who continued injecting, p < 0.005). Among those who continued injecting, HCV seropositivity was inversely associated with current non-injecting heroin use (AOR = 0.72, 95%CI 0.52-0.99). HCV incidence among persons continuing to inject was estimated as 13/100 person-years. HCV seropositive persons currently injecting cocaine were particularly likely to report behavior likely to transmit HCV. CONCLUSIONS: Similar to other locations in the US, NYC is experiencing high rates of HCV infection among persons who have begun injecting since 2000. New interventions that facilitate substitution of non-injecting for injecting drug use and that reduce transmission behavior among HCV seropositives may provide additional methods for reducing HCV transmission.

Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

OBJECTIVE: We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. METHODS: We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. RESULTS: Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. DISCUSSION: For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

Presence of the HLA-A*3101 allele in a familial case of drug reaction with eosinophilia and systemic symptoms, secondary to carbamazepine.

Anticonvulsants such as carbamazepine and phenytoin are associated with adverse skin reactions ranging from maculopapular exanthems to more severe reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and toxic epidermal necrolysis. In addition to their antiepileptic role, anticonvulsants are also used to treat pain syndromes including trigeminal neuralgia. Until recently, the associated skin reactions were thought to be unpredictable; however, the current literature suggests a genetic predisposition involving the human leucocyte antigen (HLA) in cutaneous reactions associated with carbamazepine usage. We present two familial cases of DRESS secondary to carbamazepine, in which an underlying genetic predisposition and allelic association were identified.

Combined HIV prevention, the New York City condom distribution program, and the evolution of safer sex behavior among persons who inject drugs in New York City.

Examine long term sexual risk behaviors among persons who inject drugs (PWID) in New York City following implementation of "combined" prevention programming, including condom social marketing. Quantitative interviews and human immunodeficiency virus (HIV) testing were conducted among PWID entering Beth Israel Medical Center drug treatment programs 1990-2012. Data were analyzed by four time periods corresponding to the cumulative implementation of HIV prevention interventions. 7,132 subjects were recruited from 1990 to 2012; little change in sexual behavior occurred among HIV seronegative subjects, while HIV seropositive subjects reported significant decreases in being sexually active and significant increases in consistent condom use. HIV transmission risk (being HIV positive and engaging in unprotected sex) declined from 14 % in 1990-1995 to 2 % in 2007-2012 for primary sexual partners and from 6 to 1 % for casual partners. Cumulative implementation of combined prevention programming for PWID was associated with substantial decreases in sexual risk behavior among HIV seropositives.

Scombrotoxin poisoning: an important differential diagnosis for anaphylaxis.

We report a case of scombrotoxin poisoning, an acute illness that develops within minutes to hours of eating poorly processed oily fish, such as tuna or mackerel. It presents with symptoms that can mimic an anaphylactic reaction. It is presumed to arise due to ingestion of histamine that is formed by contaminating bacteria that have flourished during periods of suboptimal refrigeration, following capture. Knowledge of this underdiagnosed malady as a potential differential diagnosis for patients presenting with symptoms suggestive of histamine release is important. It is a notifiable condition. The alternative diagnosis of anaphylaxis may have significant lifestyle implications for the patient. This article reports on one such presentation and the way that the diagnosis was explored.

A guide to anticoagulation and endocarditis prophylaxis during cutaneous surgery.

Management of perioperative antiplatelet/anticoagulation drugs and appropriate antibiotic prophylaxis for endocarditis are two controversial issues in the safe practice of cutaneous surgery. This article highlights the current best practice based on a literature review on these topics. Antiplatelet agents should be continued perioperatively whenever clinically possible, and discontinued only after consultation with the patient's cardiologist. The exception to this is primary cardiovascular disease, when antiplatelet drugs should be stopped for 1 week before surgery. Warfarin can be continued perioperatively when the international normalised ratio is controlled at < 3. The use of antibiotics in patients at risk of endocarditis has been recently reviewed by the National Institute of Health and Clinical Excellence (NICE), the American Heart Association, and the European Society of Cardiology. The advice has changed significantly over the past few years, and the routine use of antibiotics perioperatively should occur only when there is evidence of infection perioperatively at the site of surgery.

Estimates of injecting drug users at the national and local level in developing and transitional countries, and gender and age distribution.

OBJECTIVE: To present and update available national and subnational estimates of injecting drug users (IDUs) in developing/transitional countries, and provide indicative estimates of gender and age distribution. METHODS: Literature review of both grey and published literature including updates from previously reported estimates on estimates of IDU population and data sources giving age and gender breakdowns. The scope area was developing/transitional countries and the reference period was 1998-2005. RESULTS: Estimates of IDU numbers were available in 105 countries and 243 subnational areas. The largest IDU populations were reported from Brazil, China, India, and Russia (0.8 m, 1.9 m, 1.1 m, and 1.6 m respectively). Subnational areas with the largest IDU populations (35,000-79,000) are: Warsaw (Poland); Barnadul, Irtkustk, Nizhny-Novgorod, Penza, Voronez, St Petersburg, and Volgograd (Russia); New Delhi and Mumbai (India); Jakarta (Indonesia), and Bangkok (Thailand). By region, Eastern Europe and Central Asia have the largest IDU prevalence (median 0.65%) (min 0.3%; max 2.2%; Q1 0.39%; Q3 1.32%) [corrected] followed by Asia and Pacific: 0.24% (min 0.004%; max 1.47%; Q1 0.14%; Q3 1.47%) [corrected] In the Middle East and Africa the median value equals 0.2% (min 0.0003%; max 0.35%; Q1 0.11%; Q3 0.23%) [corrected] and in Latin America and the Caribbean: 0.12% (min 0.11%; max 0.69%; Q1 0.04%; Q3 0.13%) [corrected] Subnational areas with the highest IDU prevalence among adults (8-14.9%) were Shymkent (Kazakhstan), Balti (Moldova), Astrakhan, Barnadul, Irtkustk, Khabarovsk, Kaliningrad, Naberezhnyje Chelny, Penza, Togliatti, Volgograd, Voronez, and Yaroslavl (Russia), Dushanbe (Tajikistan), Ashgabad (Turkmenistan), Ivano-Frankivsk and Pavlograd (Ukraine) and Imphal, Manipur (India). 66% (297/447) of the IDU estimates were reported without technical information. Data on the IDU age/gender distributions are also scarce or unavailable for many countries. In 11 Eastern European and Central Asian countries the age group 50% of the total. The proportion of IDU men was 70%-90% in Eastern Europe and Central Asia, and there was a marked absence of data on women outside this region. CONCLUSION: Unfortunately data on IDU prevalence available to national and international policymakers is of an unknown and probably yet to be tested quality. This study provide baseline figures but steps need to be taken now to improve the reporting and assessment of these critical data.

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.

Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (Rituximab).

We describe a 54-year-old man with resistant pemphigus vulgaris. Standard therapies had afforded inadequate control and have been associated with considerable side-effects. The anti-CD20 monoclonal antibody, Rituximab (MabThera, Roche), was trialled with significant benefit. We discuss its potential mechanism of action.

Rehearsal by eye movement improves visuomotor performance in cerebellar patients.

In order to assess the effect of rehearsal by eye movement alone on visuomotor performance, the eye movements and visually guided stepping of two cerebellar patients were monitored before and after a first and second batch of eye-movement rehearsals, in which patients made saccadic eye movements to the first 6 footfall targets (in a sequence of 18) whilst standing stationary at the start of the walkway. There was a marked improvement in oculomotor and locomotor performance following the second batch of eye-movement rehearsal. Both patients showed reduced occurrence of saccadic dysmetria, evident as a significant increase in the proportion of single to multi-saccadic eye movements (from 46 to 77% for DB and from 75 to 94% for TP). This was accompanied by increased regularity and accuracy of stepping in both patients, and decreased stance and double support phase durations (one patient only). Separate testing confirmed that these improvements in eye movements and stepping did not result from simple repetition of the task. This is the first demonstration of a technique--rehearsal by eye movement--that improves the visuomotor performance of cerebellar patients. It is compelling evidence for our proposal that during visually guided stepping the locomotor control system is dependent on assistance from the oculomotor control system.

Anti-oncogenic effects of tropomyosin: isoform specificity and importance of protein coding sequences.

Suppression of muscle type isoforms of tropomyosin (TM) is a common biochemical event in malignantly transformed cells. To evaluate the role of TM proteins and isoform specificity in cellular transformation, cDNAs that consist of coding sequences of TM1 (product of beta gene) and TM2 (product of alpha gene), but lacking untranslated regions (UTRs), have been expressed separately in DT (v-Ki-ras transformed NIH3T3) cells, and elevated levels of the corresponding proteins were detected. DT cells which over express TM2 manifest growth in soft agar. Elevated levels of TM1 protein in DT cells resulted in flattened cell morphology and complete abolition of anchorage independent growth. Tumorigenesis in athymic nude mice was observed in the absence of transduced TM1 mRNA. Thus, expression of TM1 protein is sufficient for tumor suppression: the UTRs of TM1 are not required for the tumor suppressive effects. Expression of TM2 protein, on the other hand, has no effect on the transformed phenotype of DT cells. These data indicate that isoforms 1 and 2 of TMs perform distinct physiological roles.