Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination. Recommendations were supported by structured rationales, integrating evidence from one or more sources: systematic review, related evidence (evidence not from the systematic review), principles of care, and inference from evidence. RESULTS: Thirty recommendations were developed: 17 on starting DMTs, including recommendations on who should start them; 10 on switching DMTs if breakthrough disease develops; and 3 on stopping DMTs. Recommendations encompassed patient engagement strategies and individualization of treatment, including adherence monitoring and disease comorbidity assessment. The panel also discussed DMT risks, including counseling about progressive multifocal leukoencephalopathy risk in people with MS using natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate; and made suggestions for future research to evaluate relative merits of early treatment with higher potency DMTs vs standard stepped-care protocols, DMT comparative effectiveness, optimal switching strategies, long-term effects of DMT use, definitions of highly active MS, and effects of treatment on patient-specified priority outcomes. This guideline reflects the complexity of decision-making for starting, switching, or stopping MS DMTs. The field of MS treatment is rapidly changing; the Academy of Neurology development process includes planning for future updates.

Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms. METHODS: Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used. RESULTS: Twenty Cochrane reviews and an additional 73 full-text articles were selected for data extraction through an updated systematic review (completed November 2016). For people with RRMS, many DMTs are superior to placebo (annualized relapses rates [ARRs], new disease activity [new MRI T2 lesion burden], and in-study disease progression) (see summary and full text publications). For people with RRMS who experienced a relapse on interferon-ß (IFN-ß) or glatiramer acetate, alemtuzumab is more effective than IFN-ß-1a 44 µg subcutaneous 3 times per week in reducing the ARR. For people with primary progressive MS, ocrelizumab is probably more effective than placebo (in-study disease progression). DMTs for MS have varying adverse effects. In people with CIS, glatiramer acetate and IFN-ß-1a subcutaneous 3 times per week are more effective than placebo in decreasing risk of conversion to MS. Cladribine, immunoglobulins, IFN-ß-1a 30 µg intramuscular weekly, IFN-ß-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS. Suggestions for future research include studies considering comparative effectiveness, usefulness of high-efficacy treatment vs stepped-care protocols, and research into predictive biomarkers.

Utilization and impact of a pulsed-xenon ultraviolet room disinfection system and multidisciplinary care team on Clostridium difficile in a long-term acute care facility.

Health care-associated transmission of Clostridium difficile has been well documented in long-term acute care facilities. This article reports on 2 interventions aimed at reducing the transmission risk: multidisciplinary care teams and no-touch pulsed-xenon disinfection. C difficile transmission rates were tracked over a 39-month period while these 2 interventions were implemented. After a baseline period of 1 year, multidisciplinary teams were implemented for an additional 1-year period with a focus on reducing C difficile infection. During this time, transmission rates dropped 17% (P = .91). In the following 15-month period, the multidisciplinary teams continued, and pulsed-xenon disinfection was added as an adjunct to manual cleaning of patient rooms and common areas. During this time, transmission rates dropped 57% (P = .02). These results indicate that the combined use of multidisciplinary teams and pulsed-xenon disinfection can have a significant impact on C difficile transmission rates in long-term care facilities.

Disinfecting personal protective equipment with pulsed xenon ultraviolet as a risk mitigation strategy for health care workers.

The doffing of personal protective equipment (PPE) after contamination with pathogens such as Ebola poses a risk to health care workers. Pulsed xenon ultraviolet (PX-UV) disinfection has been used to disinfect surfaces in hospital settings. This study examined the impact of PX-UV disinfection on an Ebola surrogate virus on glass carriers and PPE material to examine the potential benefits of using PX-UV to decontaminate PPE while worn, thereby reducing the pathogen load prior to doffing. Ultraviolet (UV) safety and coverage tests were also conducted. PX-UV exposure resulted in a significant reduction in viral load on glass carriers and PPE materials. Occupational Safety and Health Administration-defined UV exposure limits were not exceeded during PPE disinfection. Predoffing disinfection with PX-UV has potential as an additive measure to the doffing practice guidelines. The PX-UV disinfection should not be considered sterilization; all PPE should still be considered contaminated and doffed and disposed of according to established protocols.

Non-inferiority of pulsed xenon UV light versus bleach for reducing environmental Clostridium difficile contamination on high-touch surfaces in Clostridium difficile infection isolation rooms.

The standard for Clostridium difficile surface decontamination is bleach solution at a concentration of 10 % of sodium hypochlorite. Pulsed xenon UV light (PX-UV) is a means of quickly producing germicidal UV that has been shown to be effective in reducing environmental contamination by C. difficile spores. The purpose of this study was to investigate whether PX-UV was equivalent to bleach for decontamination of surfaces in C. difficile infection isolation rooms. High-touch surfaces in rooms previously occupied by C. difficile infected patients were sampled after discharge but before and after cleaning using either bleach or non-bleach cleaning followed by 15 min of PX-UV treatment. A total of 298 samples were collected by using a moistened wipe specifically designed for the removal of spores. Prior to disinfection, the mean contamination level was 2.39 c.f.u. for bleach rooms and 22.97 for UV rooms. After disinfection, the mean level of contamination for bleach was 0.71 c.f.u. (P = 0.1380), and 1.19 c.f.u. (P = 0.0017) for PX-UV disinfected rooms. The difference in final contamination levels between the two cleaning protocols was not significantly different (P = 0.9838). PX-UV disinfection appears to be at least equivalent to bleach in the ability to decrease environmental contamination with C. difficile spores. Larger studies are needed to validate this conclusion.

The role of the healthcare environment in the spread of multidrug-resistant organisms: update on current best practices for containment.

The role of the environment in harboring and transmitting multidrug-resistant organisms has become clearer due to a series of publications linking environmental contamination with increased risk of hospital-associated infections. The incidence of antimicrobial resistance is also increasing, leading to higher morbidity and mortality associated with hospital-associated infections. The purpose of this review is to evaluate the evidence supporting the existing methods of environmental control of organisms: environmental disinfection, contact precautions, and hand hygiene. These methods have been routinely employed, but transmission of multidrug-resistant organisms continues to occur in healthcare facilities throughout the country and worldwide. Several new technologies have entered the healthcare market that have the potential to close this gap and enhance the containment of multidrug-resistant organisms: improved chemical disinfection, environmental monitoring, molecular epidemiology, self-cleaning surfaces, and automated disinfection systems. A review of the existing literature regarding these interventions is provided. Overall, the role of the environment is still underestimated and new techniques may be required to mitigate the role that environmental transmission plays in acquisition of multidrug-resistant organisms.

Injection drug use, sexual risk, violence and STI/HIV among Moscow female sex workers.

BACKGROUND/OBJECTIVES: The HIV prevalence in Eastern Europe and Central Asia continues to increase. While injection drug use (IDU) is leading factor, heterosexual transmission is on the rise. Little is known about female sex workers (FSWs) in the region despite the central role of commercial sex in heterosexual sexually transmitted infection (STI)/HIV transmission globally. The authors evaluated the prevalence of STI/HIV among Moscow-based FSWs and potential risk factors including IDU, sexual risks and violence victimisation. METHODS: Moscow-based FSWs (n=147) completed a clinic-based survey and STI/HIV testing over an 8-month period in 2005. RESULTS: HIV prevalence was 4.8%, and 31.3% were infected with at least one STI including HIV. Sexual behaviours significantly associated with STI/HIV included anal sex (adjusted odds ratio (AOR) 3.48), high client volume (three or more clients daily, AOR 2.71), recent subbotnik (sex demanded by police; AOR 2.50) and regularly being presented with more clients than initially agreed to (AOR 2.45). Past year experiences of physical violence from clients and threats of violence from pimps were associated with STI/HIV (AOR 3.14 and AOR 3.65, respectively). IDU was not significantly associated with STI/HIV. Anal sex and high client volume partially mediated the associations of abuse with STI/HIV. CONCLUSIONS: Findings illustrate substantial potential for heterosexual STI/HIV transmission in a setting better known for IDU-related risk. Many of the STI/HIV risks observed are not modifiable by FSWs alone. STI/HIV prevention efforts for this vulnerable population will benefit from reducing coercion and abuse perpetrated by pimps and clients.

Evaluation of a pulsed-xenon ultraviolet room disinfection device for impact on hospital operations and microbial reduction.

This study evaluated the use of pulsed-xenon ultraviolet (PX-UV) room disinfection by sampling frequently touched surfaces in vancomycin-resistant enterococci (VRE) isolation rooms. The PX-UV system showed a statistically significant reduction in microbial load and eliminated VRE on sampled surfaces when using a 12-minute multiposition treatment cycle.

Male sex workers in Moscow, Russia: a pilot study of demographics, substance use patterns, and prevalence of HIV-1 and sexually transmitted infections.

The Russian federation has been undergoing a concentrated epidemic of HIV-1 with high rates of infection among injecting drug users. Less is known about the relative risk and contribution to the country's HIV epidemic by other at-risk populations including sex workers and men who have sex with men. The goals of this project were to explore demographic characteristics, substance use patterns, and estimate the prevalence of sexually transmitted infections (STIs) and high-risk behaviors among male sex workers (MSW) in Moscow and to assess the feasibility of prospective cohort recruitment and retention among this population. Research design was a longitudinal study of 50 men with a six-month follow-up period. Participants were recruited through venue-based and snowball sampling methods. Results revealed an HIV prevalence at baseline of 16%; one MSW seroconverted during the follow-up period, yielding an incidence estimate of 4.8/100PY (95%CI 0.0-11.2). Twenty-four percentage were diagnosed with at least one STI: 12% had syphilis; 8% had Human Papilloma Virus (HPV); and 4% had Herpes Simplex Virus (HSV)-2. Three (6%) of the study participants had evidence of previous Hepatitis C Virus (HCV) exposure at baseline. Retention rates were poor with higher retention significantly associated with older men (OR: 13.1, 95% CI 3.3-52.5). This was the first study to evaluate baseline demographics, substance use patterns, and prevalence of infectious disease among MSW in Moscow. Identification and recruitment of this population appears to be feasible, but retention a challenge. While the sample size in the current study was small, the results also suggested that this is a population at considerable high risk for HIV. MSW in Moscow may be an important at-risk population in the Russian HIV epidemic and further research is urgently required to address their needs and explore prevention strategies.

Characterization of the emerging HIV type 1 and HCV epidemics among injecting drug users in Dushanbe, Tajikistan.

This study aimed to determine HIV, HCV, and syphilis prevalence and correlates, and to characterize the molecular epidemiology of HIV-1 among injecting drug users (IDUs) in Dushanbe, Tajikistan. A cross-sectional study assessing risk factors for HIV and HCV through an interview administered survey was conducted. A total of 491 active adult IDUs were recruited from May to November 2004 in Dushanbe, Tajikistan. HIV-1 antibody status was determined with rapid testing and confirmed with ELISA. HCV antibody testing was conducted using a BIOELISA HCV kit. HIV-1 subtyping was done on a subset with full-length sequencing. Correlates of HIV and HCV infection were assessed using logistic regression. Overall prevalence of HIV was 12.1%, HCV was 61.3%, and syphilis was 15.7%. In a multivariate logistic regression model controlling for gender and ethnicity, daily injection of narcotics [odds ratio (OR) OR 3.22] and Tajik nationality (OR 7.06) were significantly associated with HIV status. Tajik nationality (OR 1.91), history of arrest (OR 2.37), living/working outside Tajikistan in the past 10 years (OR 2.43), and daily injection of narcotics (OR 3.26) were significantly associated with HCV infection whereas being female (OR 0.53) and always using a sterile needle (OR 0.47) were inversely associated with HCV infection. Among 20 HIV-1-positive IDU with specimens available for typing, 10 were subtype A, 9 were CRF02_AG, and one was an A-CRF02_AG recombinant. Epidemics of HIV-1, HCV, and drug use are underway in Dushanbe. The molecular epidemiology is distinctive, with West African variants accounting for roughly 50% of prevalent infections. Targeted prevention programs offering both needle exchange programs and opiate substitution therapies are urgently called for to prevent the further spread of HIV and HCV in Tajikistan.

Marked ethnic differences in HIV prevalence and risk behaviors among injection drug users in Dushanbe, Tajikistan, 2004.

OBJECTIVE: To examine differences by ethnicity of HIV prevalence and correlates among injection drug users (IDUs) in Dushanbe, Tajikistan. METHODS: The researchers enrolled 489 active adult IDUs in a cross-sectional risk factor study of HIV infection. Participants were provided HIV pre-and posttest counseling and risk reduction counseling and answered an interviewer-administered questionnaire. HIV-1 status was determined with rapid tests and confirmed with ELISA. RESULTS: Participants included four ethnicities: 204 Tajiks (49.1%), 145 Russians (29.7%), 58 Uzbeks (11.9%), and 46 participants of other nationalities (9.4%). Overall prevalence of HIV-1 infection was 12% and varied significantly by ethnicity: it was highest among ethnic Tajiks, at 19.2%; lowest among Russians and Uzbeks, at 3.4%; and 13% among other nationalities. Ethnic groups differed significantly in years injecting, receiving a needle from a needle exchange program (NEP), injecting in groups, having undergone drug treatment, reported condom use, and arrest history. Among Tajiks, HIV infection was significantly associated with daily injecting (OR 2.16); reporting that narcotics were very easy to obtain (OR 2.46); having undergone drug treatment (OR 2.75), and injecting "alone" (OR 3.12). CONCLUSIONS: Ethnic differences were strongly associated with HIV prevalence and risk behaviors in this multiethnic study, and prevention efforts might need to be targeted by ethnicity.

Application of the fetal alcohol syndrome facial photographic screening tool in a foster care population.

We determined the prevalence of fetal alcohol syndrome (FAS) in a foster care population and evaluated the performance of the FAS Facial Photographic Screening Tool. All children enrolled in a Washington State Foster Care Passport Program were screened for three conditions: (1) the FAS facial phenotype from a photograph, (2) evidence of brain damage with prenatal alcohol exposure from their Health and Education passport, and/or (3) other syndromes identifiable from a facial photograph. Screen-positives received diagnostic evaluations at a FAS Diagnostic and Prevention Network clinic. The prevalence of FAS in this foster care population was 10 to 15/1000, or 10 to 15 times greater than in the general population. The screening tool performed with 100% sensitivity, 99.8% specificity, 85.7% predictive value positive, and 100% predictive value negative. We conclude that the foster care population is a high-risk population for FAS. The screening tool performed with very high accuracy and could be used to track FAS prevalence over time in foster care to accurately assess the effectiveness of primary prevention efforts.