Depression and anxiety as mediators of the relationship between sleep disturbance and somatic symptoms among adolescents on a psychiatric inpatient unit.

Background: This study investigated the relationship between sleep disturbance and somatic symptoms among adolescents residing on a psychiatric inpatient unit. Given the evidence that sleep disturbance may precede the onset of depression and anxiety and the clear associations between mood and somatic symptoms, depression and anxiety were considered as potential mediators of this relationship. Gender was tested as a potential moderator of the relationship between sleep disturbance and depression and anxiety, respectively. Method: A convenience sample of 83 adolescents completed a packet of self-report measures after admission to the unit. Measures assessed depression, sleep disturbance, anxiety, and somatic symptoms. Mediation and moderation analyses were conducted using SPSS PROCESS macro. Results: With anxiety included as a covariate, the overall indirect effect of sleep disturbance on somatic symptoms through depression was significant. No significant moderation effects were found, although females reported significantly higher levels of sleep disturbance, depression, anxiety, and somatic symptoms than males. Conclusions: Results indicated that depression mediated the relationship between sleep disturbance and somatic symptoms above and beyond the effects of anxiety. These findings suggest that interventions aimed at reducing the negative effects of sleep disturbance should also target mood in this population. Individual differences including gender should be considered when developing interventions.

Shame and stigma in association with the HCV cascade to cure among people who inject drugs.

BACKGROUND: Psycho-social experiences including shame and experienced and internalized stigma have been associated with substance use, HCV infection, and reluctance to disclose HCV status and pursue treatment. These psycho-social barriers have been examined independently for many chronic diseases, including HCV, but to our knowledge have not been quantitatively explored in a large multi-site US-based sample of people who inject drugs (PWID) in HCV treatment. METHODS: We examine baseline relationships with HCV-stigma and engagement across the HCV treatment cascade as well as baseline and longitudinal relationships between shame and engagement across the HCV treatment cascade including treatment initiation, adherence, completion, and sustained virologic response (SVR) among a multi-site sample of PWID with HCV, where N=755 were randomized to the pragmatic trial comparing HCV treatment outcomes in modified directly observed treatment (mDOT) or patient navigation, and N=623 initiated treatment. RESULTS: While cross-sectional assessments of shame and HCV-stigma were not associated with engagement across the HCV treatment cascade, those whose shame scores decreased compared to those who reported consistently high and increasing levels of shame were significantly more likely to complete HCV treatment (aOR=5.29; 95%CI: 1.56,18.00) and achieve SVR (aOR=6.32; 95%CI: 1.61, 24.87). CONCLUSION: Results underscore the relationships between lower levels of shame and health-related behavior and treatment outcomes among PWID and suggest SVR achievement may contribute to reductions in shame or that reductions in shame may contribute to continued treatment and thus SVR.

Personality predictors of 6-month readmission in adult psychiatric inpatients.

Readmission of psychiatric inpatients is highly prevalent and places a significant financial burden on the healthcare system. Rehospitalisation is often used as a metric of quality of care in psychiatric settings, but little is known about how specific personality traits impact readmission in adult psychiatric inpatients. A convenience sample of 94 adults (mean age = 36.8 years; female = 54.3%; European American = 76.6%) at an inpatient psychiatric hospital completed the Personality Inventory for DSM-5-Brief Form (PID-5-BF; American Psychiatric Association, 2013); demographic and medical information and readmission data were extracted via chart review. Poisson regression was used to predict number of readmissions at 6 months after discharge from PID-5-BF domain scores of Negative Affectivity, Detachment, Antagonism, Disinhibition and Psychoticism. Twenty-three patients (24.5%) were readmitted at least once by 6-month follow-up. Higher PID-5-BF Negative Affectivity domain scores predicted greater number of readmissions at 6 months (incidence rate ratio (IRR) = 1.14, robust standard error (RSE) = 0.05, p < .01, 95% confidence interval [1.04, 1.25]). The other PID-5-BF domain scores were not significantly related to number of readmissions. Thus, greater negative affect, indicative of higher trait neuroticism, heightened experience of negative emotions and poor self-concept, was a significant personality predictor of readmission in the study. These results suggest that assessing this trait domain might help to identify psychiatric inpatients at greater risk for readmission and determine those most in need of enhanced services to reduce rehospitalisation.

Real-World User Experiences with a Digital Pill System to Measure PrEP Adherence: Perspectives from MSM with Substance Use.

Once-daily oral pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV transmission, but adherence can be challenging for men who have sex with men (MSM) who use substances. A novel method for directly measuring ingestion events is a digital pill system (DPS), which comprises an ingestible radiofrequency emitter that signals a wearable Reader device upon PrEP ingestion, relaying ingestion data to a wearable Reader device and then to a smartphone application. Qualitative interviews were conducted with 15 MSM with non-alcohol substance use following an open-label pilot demonstration trial involving use of the DPS to measure PrEP adherence for 90 days. The purpose of this qualitative investigation was to understand overall user experiences and potential barriers and facilitators to using the DPS to measure PrEP adherence among MSM. The DPS was largely perceived as acceptable, novel, and valuable, with most participants reporting that the system was easily integrated into their daily routines. Technological and design factors, especially related to the wearable Reader, impacted participants' interest in using the technology long-term; several suggested improvements were discussed.Trial Registration ClinicalTrials.gov: NCT03842436.

Race, trust, and COVID-19 vaccine hesitancy in people with opioid use disorder.

OBJECTIVE: Vaccination against coronavirus disease 2019 (COVID-19) is a promising avenue for arresting the COVID-19 pandemic, yet suboptimal rates of vaccine uptake in at-risk groups may hinder efficacy and worsen existing health disparities. People with opioid use disorder (OUD) are likely to face increased vulnerability to COVID-19 due to a confluence of biological and social risk factors. We sought to assess factors associated with willingness to vaccinate against COVID-19 in people with OUD. METHOD: Phone surveys were conducted from May to October 2020 with participants enrolled in an urban methadone maintenance program (MMP). Participants were adults who met DSM-5 criteria for OUD and reported injection drug use or sexual risk behavior. Participants were asked about their willingness to receive a highly or partially effective vaccine. Provider trust was assessed using the Trust in Physician scale. Multinomial regression was used to assess demographic and psychosocial factors related to vaccination willingness. RESULTS: We surveyed 109 people with OUD enrolled in a MMP (M = 47 years; 56% women; 59% White, 23% Black/African American, 14.4% Hispanic/Latinx; 1.8% other). Participants who identified as Black or African American were significantly less likely to endorse willingness to use a partially effective COVID-19 vaccine (adjusted odds ratio [aOR] = .10; 95% confidence interval (CI) [.02, .61], p = .012), although not necessarily less willing to receive a highly effective vaccine (aOR = .40; 95% CI [.09, 1.73], p = .219; n.s.). Trust in physician was positively associated with willingness to use a partially effective vaccine (aOR = 1.12; 95% CI [1.02, 1.23], p = .017), but was not significantly associated with willingness to receive a highly effective vaccine (aOR = 1.07; 95% CI [.98, 1.16], p = .162, n.s) Conclusions: Proactive outreach from trustworthy sources will be needed to counter vaccine hesitancy in people with OUD, especially among Black Americans with OUD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The impact of depression and post-traumatic stress symptoms on physical health perceptions and functional impairment among sexual minority men living with HIV with histories of trauma.

Mental health symptoms may compromise health-related quality of life (HRQOL), including among men who have sex with men (MSM) living with HIV, who experience high rates of trauma and other stressors. This study sought to examine the relative contributions of post-traumatic stress disorder (PTSD) symptoms, depression symptoms, and biological indices of HIV disease status on HRQOL in this population. Participants were 79 MSM with HIV (49% White; 35% Black; 8% Hispanic/Latinx) with trauma histories (52% met current PTSD diagnostic criteria). HRQOL outcomes were general perceptions of health (0-100 visual analog scale) and functional disability (WHODAS 2.0). Dominance analysis was applied to examine the relative share of variance in these outcomes accounted for by PTSD symptom severity, depression symptom severity, viral suppression status, and CD4 count. Depression symptom severity accounted for 70% and 92% of variance in perceived health, respectively, across models (p's < 0.05). Both PTSD symptom severity (45%) and depression symptom severity (43%) scores also accounted for significant variance in functional disability (p's < 0.05). Medical indices of HIV disease progression did not explain significant variance in HRQOL in any model. A trauma-informed approach may aid clinicians in interpreting reports of health and physical functioning in MSM with HIV.

Development of a digital pill and respondent behavioral intervention (PrEPSteps) for HIV pre-exposure prophylaxis adherence among stimulant using men who have sex with men.

The efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention in men who have sex with men (MSM) is contingent upon consistent adherence. Digital pill systems (DPS) provide real-time, objective measurement of ingestions and can inform behavioral adherence interventions. Qualitative feedback was solicited from MSM who use stimulants to optimize a cognitive behavioral therapy (CBT)-based intervention (LifeSteps), used in conjunction with a DPS, to promote PrEP adherence (PrEPSteps). Seven focus groups and one individual qualitative interview were conducted in Boston, MA with cisgender, HIV-negative MSM who reported stimulant use and current PrEP use or interest. Focus groups and interviews explored reactions to the DPS and PrEPSteps messaging components: contingent reinforcement (CR), corrective feedback (CF), LifeSteps, and substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT). Quantitative assessments were administered. Qualitative data were analyzed using applied thematic analysis. Twenty MSM participated. Most were White (N = 12), identified as homosexual or gay (N = 15), and college-educated (N = 15). Ages ranged from 24 to 68 years (median 35.5). Participants were willing to engage with the DPS and viewed it as beneficial for promoting adherence. Confirmatory CR messages were deemed acceptable, and a neutral tone was preferred. CF messages were viewed as most helpful and as promoting individual responsibility. LifeSteps was perceived as useful for contextualizing nonadherence. However, SBIRT was a barrier to DPS use; concerns around potential substance use stigma were reported. MSM who use stimulants were accepting of the DPS and PrEPSteps intervention. CR, CF, and LifeSteps messages were viewed as helpful, with modifications pertaining to tone and content; SBIRT messages were not preferred.

DigiPrEP: A Pilot Trial to Evaluate the Feasibility, Acceptability, and Accuracy of a Digital Pill System to Measure PrEP Adherence in Men Who Have Sex With Men Who Use Substances.

BACKGROUND: Adherence to once daily oral preexposure prophylaxis (PrEP) for HIV prevention can be challenging for men who have sex with men (MSM) with substance use. Digital pill systems (DPS) comprise a radiofrequency emitter integrated into a gelatin capsule containing PrEP, which transmits data to a wearable Reader following ingestion, thereby enabling direct, real-time adherence measurement. This study evaluated the feasibility, acceptability, and accuracy of a DPS to measure PrEP adherence. METHODS: A 90-day, single-arm, open-label, pilot demonstration trial was conducted with adult, cisgender, HIV-negative MSM on PrEP with nonalcohol substance use. Feasibility was measured via DPS engagement and timeline followback. Acceptability was assessed via qualitative user experience interviews. Accuracy was evaluated via DPS performance metrics, pill counts, and DBS to quantify tenofovir diphosphate. RESULTS: Sixteen MSM enrolled (median age, 32 years), and 15 completed the study. Engagement remained stable over time. Emergent nonadherence patterns included intercurrent substance use. The DPS was largely acceptable based on interviews; the predominant barrier to use was the Reader. DPS-recorded ingestions totaled 1099, including 83.9% were detected by Reader and 16.1% were reported manually. The DPS recorded 92.2% of 1192 total expected ingestions per pill counts. Point-biserial correlation (R = 0.58; 95% CI: 0.21 to 0.80; P = 0.047) and Pearson correlation (month 1: R = 0.85; 95% CI: 0.57 to 0.95; P = 0.0002; month 3: R = 0.75; 95% CI: 0.17 to 0.94; P = 0.0197) showed strong correlations between DPS-recorded adherence and tenofovir diphosphate in dried blood spots. CONCLUSION: DPS are a feasible, acceptable, and accurate method of measuring PrEP adherence in MSM with substance use. Future investigations should incorporate DPS into behavioral interventions targeting nonadherence.

Differential impacts of COVID-19 across racial-ethnic identities in persons with opioid use disorder.

OBJECTIVE: The COVID-19 pandemic has exacerbated health disparities, particularly among at-risk people with opioid use disorder (OUD). We sought to characterize the direct and indirect impacts of COVID-19 on this group to understand how the pandemic has affected this group, this group's public health response to COVID-19, and whether there were differences by race/ethnicity. METHODS: This study recruited its sample from a drug treatment setting in the northeast region of the United States. We surveyed 110 individuals on methadone as treatment for OUD and assessed COVID-19-related impacts on their health behaviors and other indices of social, physical, and mental well-being, including sexual health behaviors, substance use, mental health status, health care access, income, and employment. RESULTS: Our findings highlight overall increases in depression, anxiety, loneliness, and frustration among the sample of people with OUD; the study also observed decreases in financial stability. Significant differences between groups indicated a greater financial burden among racial-ethnic minorities; this subgroup also reported greater direct adverse effects of COVID-19, including being more concerned about contracting COVID-19, not being able to get a COVID-19 test, and knowing someone who had died from COVID-19. A greater proportion of Whites indicated increases in alcohol consumption and non-prescription drug use than did racial-ethnic minorities. CONCLUSIONS: Treatment providers must be vigilant in managing direct and indirect outcomes of COVID-19 among people with OUD. Findings highlight the need to develop culturally competent, differentiated interventions in partnership with community-based organizations to meet the unique challenges that the COVID-19 pandemic presents for people in treatment for OUD.

A Brief Training Program to Support the Use of a Digital Pill System for Medication Adherence: Pilot Descriptive Study.

BACKGROUND: Digital pill systems (DPSs), which comprise ingestible radiofrequency sensors integrated into a gelatin capsule that overencapsulates a medication, can directly measure ingestion events. OBJECTIVE: Teaching users to operate a DPS is vital to ensure the collection of actionable ingestion and adherence data. In this study, we aim to develop and pilot a training program, grounded in the Technology Acceptance Model, to instruct individuals on DPS operation. METHODS: A two-part training program, comprising in-person and text message-based components, was used with HIV-negative men who have sex with men with nonalcohol substance use, who had enrolled in a 90-day pilot demonstration study using the DPS to measure adherence to pre-exposure prophylaxis. We assessed the number of responses to text check-ins, the number and types of episodes where technical support was requested, the resolutions of such issues, and engagement with the program over the study period. Participant feedback on the program was evaluated through qualitative user experience interviews. RESULTS: A total of 15 participants were enrolled in and completed the program. Seven technical challenges related to DPS operations were reported across 5 participants. Most commonly, participants requested support connecting the wearable Reader device with their smartphone, charging the Reader, and operating the mobile app. A total of 6 issues were resolved asynchronously or in real time via phone; 1 required in-person evaluation and resolution. Preliminary qualitative findings indicate that both the in-person and remote follow-up components of the training program were perceived as acceptable. Suggested improvements included repeated DPS refresher sessions at in-person follow-up visits and enhanced written materials for the independent resolution of technological issues. CONCLUSIONS: A brief two-part DPS training program, drawing from individuals' experiences and from the Technology Acceptance Model, can provide valuable insights for users. The program also identifies and addresses several areas of actual or potential challenges related to operating a DPS and allows for the resolution of such issues within the first week of DPS use.

Developing a cognitive dysfunction risk score for use with opioid-dependent persons in drug treatment.

BACKGROUND: Cognitive dysfunction is common in persons seeking medication for opioid use disorder (MOUD) and may hinder many addiction-related services. Brief but accurate screening measures are needed to efficiently assess cognitive dysfunction in these resource-limited settings. The study aimed to develop a brief predictive risk score tailored for use among patients in drug treatment. METHODS: The present study examined predictors of mild cognitive impairment (MCI), objectively assessed via the NIH Toolbox, among 173 patients receiving methadone as MOUD at an urban New England drug treatment facility. Predictors of MCI were identified in one subsample using demographic characteristics, medical chart data, and selected items from the Brief Inventory of Neuro-Cognitive Impairment (BINI). Predictors were cross-validated in a second subsample using logistic regression. Receiver operating curve (ROC) analyses determined an optimal cut-off score for detecting MCI. RESULTS: A cognitive dysfunction risk score (CDRS) was calculated from patient demographics (age 50+, non-White ethnicity, less than high school education), medical and substance use chart data (history of head injury, overdose, psychiatric diagnosis, past year polysubstance use), and selected self-report items (BINI). The CDRS discriminated acceptably well, with a ROC curve area of 70.6 %, and correctly identified 78 % of MCI cases (sensitivity = 87.5 %; specificity = 55.6 %). CONCLUSIONS: The CDRS identified patients with cognitive challenges at a level likely to impede treatment engagement and/or key outcomes. The CDRS may assist in efficiently identifying patients with cognitive dysfunction while requiring minimal training and resources. Larger validation studies are needed in other clinical settings.

Intersecting Barriers to PrEP Awareness and Uptake in Black Men Who Have Sex with Men in Atlanta, GA: a Syndemic Perspective.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can sharply reduce HIV transmission risk, yet has not been widely adopted among those at highest risk for HIV, including Black men who have sex with men (BMSM). To better understand the evolving landscape of PrEP uptake in this at-risk population, we sought to examine psychosocial factors associated with PrEP uptake in a sample of BMSM residing in the Atlanta, GA, area. METHOD: BMSM were recruited through online social media, LGBT venues, and participant referral, and self-reported demographic and psychosocial information via computer-assisted self-interview. Multivariate logistic regression was used to examine psychosocial factors associated with PrEP uptake. RESULTS: In 293 BMSM, most (N = 260; 88.7%) reported awareness of PrEP yet few (N = 30; 10.1%) reported ever having taken PrEP. BMSM reporting more syndemic conditions were less likely to be current PrEP users (OR = 0.59; 95% CI: 0.36, 0.96). BMSM reporting recent condomless anal sex (CAS) with a partner met online (adjusted odds ratio (aOR) = 2.53; 95% CI: 1.07, 5.93), or who reported having chlamydia (aOR = 8.21; 95% CI: 1.42, 47.67) or STI-related symptoms (aOR = 4.35; 95% CI: 1.32, 14.37) in the past 3 months, or genital warts in their lifetime (aOR = 7.74; 95% CI: 2.47, 24.21) were more likely to have ever used PrEP. Sexual orientation stigma from health care providers was negatively associated with PrEP uptake (OR = 0.81, 95% CI: 0.68, 0.95) among BMSM reporting recent CAS and multiple partners. CONCLUSION: Syndemic and stigma theories may inform strategies for improving PrEP uptake in BMSM.

Assessing an Epidemic: Utility of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Level 2 Substance Use Screener in Adult Psychiatric Inpatients.

BACKGROUND: Inpatient psychiatric hospitals provide an important point of care for assessing and stabilizing substance use and for facilitating linkage to appropriate treatment. Toxicology screening provides a key measure of substance use yet may miss many cases of substance use because of variable windows of detection and the limited scope of substances assessed. This study assesses the utility of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Level 2 Substance Use screener as a supplemental tool for identifying substance use by self-report within an inpatient psychiatric hospital setting. METHODS: From a larger sample of 97 adult psychiatric inpatients, 60 who underwent drug toxicology testing and completed the DSM-5 screener were assessed. We examined the sensitivity and specificity of the self-report screener in comparison with drug toxicology test results collected by chart review. RESULTS: Sensitivity of the DSM-5 screener varied across substances assessed: The self-report measure identified 100% of individuals who tested positive for opioid use, 83% who tested positive for cannabis use, 50% who tested positive for cocaine use, and 37% who tested positive for benzodiazepine use. The self-report measure also identified 27 instances among 60 participants in which substance use identified by self-report was not detected by toxicology testing. CONCLUSION: The brief and easily administered DSM-5 Level 2 Substance Use screener shows promise for improving identification of substance use in an inpatient psychiatric hospital setting. This measure may also provide psychiatric inpatient nursing staff with a means of working collaboratively with patients to assess substance use and coordinate appropriate treatment plans.

Substance Use, HIV Serostatus Disclosure, and Sexual Risk Behavior in People Living with HIV: An Event-Level Analysis.

People living with HIV (PLWH) face difficult decisions about disclosing their HIV status to new sexual partners. Alcohol and other drug use could impact these decision-making processes and subsequent sexual risk behavior. We sought to examine the event-level relationships between substance use, HIV disclosure, and condom use in PLWH and their first-time HIV-negative or unknown status sexual partners. Adult PLWH were recruited from care settings in a southeastern U.S. city. Participants reported their sexual behavior for 28 consecutive days via text message prompts. We employed multilevel covariation in a causal system to examine the event-level relations between substance use and condom use. We proposed that this relationship would be mediated by HIV disclosure and moderated by viral suppression status. A total of 243 participants (83% male, 93% Black) reported 509 sexual events with first-time HIV-negative/unknown status sexual partners. Substance use at the time of sex was negatively associated with disclosure in PLWH with suppressed viral load (OR 0.29, ß = - 1.22, 95% CI [- 2.42, - 0.03], p = .045), but differentially associated with condom use in PLWH with detectable versus undetectable viral load. In PLWH with viral suppression, participants who always disclosed versus who never disclosed their HIV status were more likely to use condoms (ß = 1.84, 95% CI [0.35, 3.53], p = .017), but inconsistent disclosers were less likely to use a condom after disclosing (OR 0.22, 95% CI [0.07, 0.68], p = .008). Event-level analysis offers a more nuanced understanding of the proximal (substance use, HIV disclosure) and person-level (substance use, viral load) determinants of HIV transmission risk behavior in PLWH.

PROMIS®-assessed sleep problems and physical health symptoms in adult psychiatric inpatients.

OBJECTIVE: The goal of this study was to assess the relationship between sleep problems and somatic symptoms in a sample of adult psychiatric inpatients and evaluate the utility of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Sleep Disturbance Measure as a predictor of physical health symptom severity within this population. METHOD: Ninety-five adults were assessed following admission to an inpatient psychiatric hospital. Demographic and medical information were extracted via chart review. Participants completed the PROMIS® Sleep Disturbance Measure-Short Form, the PROMIS® Depression Measure-Short Form, the DSM-5 Cross-Cutting Symptom Measure (CCSM), and the Patient Health Questionnaire-Physical Symptoms (PHQ-15). A hierarchical linear regression was conducted predicting severity of physical symptoms from PROMIS® Sleep scores, while controlling for gender, depression scores, number of medications, number of psychiatric diagnoses, and whether the participant was undergoing detoxification. RESULTS: Data showed that 50% of participants reported medium/high levels of physical health symptoms, and 41% reported moderate/severe levels of sleep disturbance. A positive screen on the CCSM Somatic Symptoms domain was a significant predictor of more self-reported physical health symptoms (ß = 0.278, p = .005, 95% CI [1.24, 6.61]). When PROMIS® Sleep scores were included, the model accounted for significantly more variability in physical health symptom scores (ΔR2 = 0.085, F = 9.150, p < .001), and the CCSM Somatic Screener remained a significant predictor (ß = 0.230, p = .013, 95% CI [0.70, 5.79]). PROMIS® Sleep scores significantly predicted physical health symptom scores (ß = 0.364, p = .001, 95% CI [0.11, 0.42]). CONCLUSIONS: A significant proportion of psychiatric inpatients report elevated levels of physical health symptoms, and greater sleep disturbance is a significant predictor of somatic symptoms severity. The PROMIS® Sleep Disturbance Measure may be a better predictor of physical health symptoms among psychiatric inpatients than the CCSM alone. The PROMIS® Sleep Disturbance Measure may also serve as a useful screening and outcome assessment tool in future clinical and research work among this understudied population. Identifying and intervening with psychiatric inpatients at risk for poor sleep and more severe physical health symptoms has the potential to positively impact patients' hospitalization and postdischarge outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Safety of Repeated Injections of Sodium Hyaluronate (SUPARTZ) for Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Though there is no consensus on its efficacy, knee osteoarthritis is symptomatically managed with intra-articular hyaluronic acid (IAHA). Recent reports suggest that IAHA may delay the need for total knee replacement, with the magnitude of delay proportional to the number of injection series. However, the safety of repeated injection series is reported to vary between commercial products. This report describes a systematic review of safety data on repeated treatment courses of SUPARTZ. DESIGN: We performed a systematic search of MEDLINE, Cochrane database, EMBASE, Web of Science, Google Scholar, and unpublished data. We included all human randomized controlled trials or observational studies with adverse event (AE) data for SUPARTZ in knee osteoarthritis. Two independent reviewers extracted data and evaluated study quality. Data were analyzed separately for the first and subsequent series of injections. RESULTS: The primary sources for repeated-injection data on SUPARTZ were a postmarket registry (N = 7404), 4 prospective studies (N = 127 total), and a retrospective study (N = 220). None of the sources reported increased frequency or severity of AEs with repeated injections. In the registry, 95% of multiple-injection-series patients who reported an AE did so during the first series. None of the AEs was serious, and most resolved spontaneously without medical intervention. The overall adverse event rate after repeat courses of SUPARTZ was 0.008 (95% confidence interval: 0.001-0.055). CONCLUSIONS: Multiple courses of SUPARTZ injections appear to be at least as safe, and probably safer, than the first course. This study supports the safety of repeat courses of SUPARTZ injections for knee osteoarthritis.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial.

BACKGROUND: We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among patients with type II bipolar disorder (BD, BD-II) more than patients with type I BD (BD-I). METHODS: Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, BD-I (n = 21) and BD-II (n = 49) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then randomized openly to continue or discontinue ADs for up to 3 years. Outcomes were episode recurrences and changes in standardized symptom ratings. RESULTS: In follow-up averaging 1.64 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in BD-I than in BD-II (for type II, mean [standard deviation] decrease in depressive episodes per year, 0.21 [0.26]; for type I, mean (SD) decrease, 0.35 [0.15]). Subjects with BD-II who continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. CONCLUSIONS: The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I, except somewhat lower risk of manic/hypomanic episodes.