Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Disturbances to energy metabolism in juvenile lake sturgeon (Acipenser fulvescens) following exposure to niclosamide.

Since the 1960s, invasive sea lamprey (Petromyzon marinus) populations in the Laurentian Great Lakes have been controlled by applying two chemicals, 3-trifluoromethyl-4-nitrophenol (TFM) and 2',5-dichloro-4'-nitrosalicylanilide (niclosamide, aka. Bayluscide®), to streams infested with larval sea lamprey. These "lampricide" applications primarily rely on TFM, and are often combined with 1-2% niclosamide, which increases treatment effectiveness. Niclosamide is also used alone to treat lentic habitats and in rivers with high discharge. However, little is known about niclosamide's possible adverse physiological effects on non-target organisms. Of particular concern is the lake sturgeon (Acipenser fulvescens), which is threatened throughout the Great Lakes basin where its habitat often overlaps with larval lamprey. Because niclosamide is believed to impair ATP production by uncoupling oxidative phosphorylation, we determined how it altered metabolic processes and acid-base balance in young-of-the-year (YOY) lake sturgeon exposed to their 9-h LC50 of niclosamide (0.11 mg L-1) for 9 h. Exposure to niclosamide led to decreased brain ATP and glucose reserves, and increased lactate, with no effect on brain glycogen. In contrast, substantial (60%) reductions in glycogen were observed in liver, suggesting that hepatic glycogen reserves were mobilized to meet the brain's glucose requirements when ATP supply was impaired during niclosamide exposure. Disturbances in carcass included reduced phosphocreatine (65-70%), 2- and 4-fold increases in pyruvate and lactate, and a slight metabolic acidosis, characterized by a 0.1 unit decrease in intracellular pH (pHi). Each of these disturbances were corrected within 24 h following depuration in clean (niclosamide-free) water. We conclude that if lake sturgeon survive exposure to niclosamide, they are able to rapidly replenish their energy stores (glycogen, ATP, phosphocreatine) and correct any corresponding metabolic disturbances within 24 h.

Reversible disruptions to energy supply and acid-base balance in larval sea lamprey exposed to the pesticide: Niclosamide (2',5-dichloro-4'-nitrosalicylanilide).

Since the 1960s, chemical control of larval sea lamprey has been achieved using the pesticides 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide (Bayluscide®). Much more potent, niclosamide is often used as an adjuvant for TFM, and on its own to treat lentic habitats, rivers with high discharge and currents, and for population surveys. Yet, little is known about its mode of action or physiological effects on sea lamprey. Like TFM, niclosamide is thought to impair mitochondrial ATP production by uncoupling oxidative phosphorylation. We therefore tested the hypothesis that niclosamide would result in metabolic perturbations and disturbances to acid-base balance in larval lamprey due to their need to balance ATP supply with ATP demands. When larval sea lamprey were exposed to the nominal 9-h niclosamide LC50 (0.11 mg L-1) over 9 h, it resulted in significant decreases in brain, phosphocreatine (35 %) and glycogen (50 %), accompanied by a 5-fold increase in lactate. In carcass, there were 25-30 % decreases in glycogen, corresponding increases in pyruvate and lactate, and a pronounced 0.5 unit decrease in intracellular pH. Calculation of the NAD+/NADH ratio in the carcass indicated that neither oxygen delivery nor the flux of reducing equivalents through the mitochondrial electron transport chain were impaired by niclosamide, supporting the hypothesis that niclosamide interferes with mitochondrial ATP production by uncoupling oxidative phosphorylation. Thus, greater reliance on glycogen, characterized by higher rates of glycolysis, temporarily mitigates the corresponding shortfall in ATP supply caused by niclosamide. Notably, all lamprey that survived niclosamide exposure readily restored ATP, phosphocreatine, glycogen and acid-base balance after recovery in niclosamide-free water. This resilience suggests that sea lamprey that survive or escape niclosamide treatment could compromise sea lamprey control efforts by subsequently completing their larval stage and developing into parasitic juvenile sea lamprey that could ultimately threaten Great Lake's fisheries populations.

The lampricide 3-trifluoromethyl-4-nitrophenol causes temporary metabolic disturbances in juvenile lake sturgeon (Acipenser fulvescens): implications for sea lamprey control and fish conservation.

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is applied to rivers and streams draining into the Laurentian Great Lakes to control populations of invasive sea lamprey (Petromyzon marinus), which are ongoing threats to fisheries during the lamprey's hematophagous, parasitic juvenile life stage. While TFM targets larval sea lamprey during treatments, threatened populations of juvenile lake sturgeon (Acipenser fulvescens), particularly young-of-the-year (<100 mm in length), may be adversely affected by TFM when their habitats overlap with larval sea lamprey. Exposure to TFM causes marked reductions in tissue glycogen and high energy phosphagens in lamprey and rainbow trout (Oncorhynchus mykiss) by interfering with oxidative ATP production in the mitochondria. To test that environmentally relevant concentrations of TFM would similarly affect juvenile lake sturgeon, we exposed them to the larval sea lamprey minimum lethal concentration (9-h LC99.9), which mimicked concentrations of a typical lampricide application and quantified energy stores and metabolites in the carcass, liver and brain. Exposure to TFM reduced brain ATP, PCr and glycogen by 50-60%, while lactate increased by 45-50% at 6 and 9 h. A rapid and sustained depletion of liver glucose and glycogen of more than 50% was also observed, whereas the respective concentrations of ATP and glycogen were reduced by 60% and 80% after 9 h, along with higher lactate and a slight metabolic acidosis (~0.1 pH unit). We conclude that exposure to environmentally relevant concentrations of TFM causes metabolic disturbances in lake sturgeon that can lead to impaired physiological performance and, in some cases, mortality. Our observations support practices such as delaying TFM treatments to late summer/fall or using alternative TFM application strategies to mitigate non-target effects in waters where lake sturgeon are present. These actions would help to conserve this historically and culturally significant species in the Great Lakes.

Self-reported disease severity in women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), pathology with net feminine predominance, is one of the most complex autoimmune diseases and has major impact on patients' life. The aim is to identify patient and disease-related factors associated with self-perceived disease severity in female SLE patients. This cross-sectional study enrolled 73 women fulfilling the 2012 Systemic Lupus International Collaborating Clinic (SLICC) criteria. SLE disease activity was assessed by the Systemic Lupus Activity Measure (SLAM) score and overall damage by the SLICC/American College of Rheumatology (ACR) index. Patients' general characteristics, associated conditions as well as SLE specific clinical involvements and therapeutic principles were also noted. Fatigue was assessed by FACIT-fatigue scale. Self-perceived disease severity was assessed using numerical rating scales (1-10 NRSs), to evaluate the disease severity at inclusion (1-10 NRS now) and worst severity anytime during disease history (1-10 NRS worst ever). In regard to worst ever lupus severity, 54.8% of patients responded with 9 or 10, while none with 1 or 2 even if only 22.9% of the patients responded with 7 or more for disease severity at inclusion (1-10 NRS now). Women with higher 1-10 NRS now answers had also higher 1-10 NRS worst ever, SLAM, SLICC, and FACIT-fatigue scores. They associated more frequently anxiety/depression diagnosis, antiphospholipid syndrome, joint involvement as well as treatments with corticosteroids. Self-reported disease severity worst ever, anxiety/depression diagnosis, fatigue, and the daily dose of corticosteroids were independently associated with patients' perception on lupus severity at inclusion: OR (95% CI), 2.13 (1.15-3.94) p = 0.017, 6.67 (1.11-39.97) p = 0.038, 1.10 (1.02-1.19) p = 0.018, and 1.11 (1.02-1.21) p = 0.020, respectively. The vast majority of patients identified severe and very severe events during their disease history, results that raise awareness of burden concerning lupus occurrence in women's life. Self-perceived lupus severity is multifactorial, influenced also by factors less considered in the SLE management like fatigue and the depression/anxiety disorders, but also by the previous patient's experience.

Paternal exposure to antirheumatic drugs-What physicians should know: Review of the literature.

Reproduction capacity and long-term preserved hormonal function are important aspects with big impacts on patients' quality of life. Updated information on the interaction between drug therapy and reproductive function is essential when discussing family planning with patients. Currently, limited data is published regarding paternal exposure to different medications. Thus, it may be a challenge for the practitioner to choose the right therapy for a young male patient. Therefore we reviewed the literature, for effects of antirheumatic drugs on male gonadal function with a focus on spermatogenesis and offspring.

The relationship between disease activity, quality of life, and personality types in rheumatoid arthritis and ankylosing spondylitis patients.

We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.

Different effects of anti-TNF-alpha biologic drugs on the small bowel macroscopic inflammation in patients with ankylosing spondylitis.

BACKGROUND & AIMS: Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. METHODS: Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. RESULTS: The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, p<0.001). 16 patients (42.1%) were on anti-TNF alpha therapy (Adalimumab (n = 5), Infliximab (n = 5) or Etanercept (n = 6)).31.3% of them used NSAIDs simultaneously, compared with 77.3% of the other patients (p<0.01). Their Lewis scores were lower compared to the other patients for the entire small bowel (306 ± 164 vs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). CONCLUSION: Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).

Socio-economical factors that influence the perception of quality of life in patients with osteoporosis.

The appearance of osteoporosis in elders and the growth of the frequency which it is diagnosed with as we approach patients who are older and older, makes this health problem very important in the societies in which a high number of persons reach old age. These societies, usually belonging to economically advanced jurisdictions, are the first interested in the way health expenses can balance the benefits of the quality of life acquired in these groups of population. The evaluation of the quality of life has become a very important process, which still raises methodological problems to the researchers. The aim of this study was to analyze to what extent the factors involved in defining the quality of life by the patients modified according to the existence of osteoporosis as a defined but also as a perceived disease, as far as it is considered a serious or less serious affection by each patient. 210 female patients participated in the study. The statistical analysis was done by using SPSS 22.0 (IBM Corp. - U.S.A.). p < 0,05 was used as a limit for the statistical significance. Descriptive and analytical analyses were made by following Pearson correlation index in cases of normal distributions, the comparison between groups was made by using t-Student test, respectively chi square test in the cases which required its use. The current study highlights a direct relationship between the quality of life, as it is perceived by the patients, and the quality of the health status, which is more important than the relationship between the quality of life and the other objectives measured by WHOQOL scale. This study also shows that for the Romanian patient diagnosed with osteoporosis, who is enclosed in the age limits of this study, the health status represents the main driver of monitoring the quality of life.

Evaluation of adherence to anti-osteoporosis treatment from the socio-economic context.

Osteoporosis is a disease characterized by the reduction of the bone mass and the modification of the bone architecture, which leads to the risk of fracture of the fragile bones, this being the main clinical consequence of the disease. At the same time, osteoporosis is not only a problem by itself, but it is very important from the point of view of the consequences it may produce. Among its consequences, fractures should be mentioned especially in elders, their presence finally leading to an important decrease in the quality of life or even to death. Osteoporosis affects a high amount of persons, preponderantly elders, being considered a very important problem as the society we are talking about deals with the problem of aging. Socio-economical factors and their impact in the development of different pathologies have been seriously analyzed, especially by the western school of medicine. The aim of the current study is to evaluate the adherence to the treatment for osteoporosis of patients diagnosed with osteoporosis or in whom this diagnosis was taken into consideration by the physician, according to some characteristics identified as being the most relevant by a group of specialists. 210 patients were evaluated in this study during January 2011 and December 2013. This study highlighted the way patients with a real or presumptive diagnosis of osteoporosis adhere to the treatment for this disease according to the conditions considered relevant by a team of rheumatologists. It is important to notice that, still from the beginning, once the duration of the disease grows, patients become more and more conscious of the seriousness of the disease and more and more of them adhere to the treatment.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients.

BACKGROUND: The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. AIM: To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. METHODS: 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aß2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aß2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aß2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. CONCLUSIONS: IgG aß2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.

Sudden cardiac death due to triple myocardial bridging associated with atypical coronary topography.

Myocardial bridging (MB) is defined as the presence of an intramural course of a coronary artery, most likely caused by a defect in resorption of the musculature that encircles the epicardial arteries during morphogenesis. We present a case of the young man who died suddenly while playing professional football and whose cause of death was acute myocardial infarction associated with multiple myocardial bridges (1.8 cm on the anterior interventricular artery, 1.3 cm on the circumflex artery, and an intramyocardial trajectory of the posterior interventricular artery), and discuss the causes of death and possible consequences of this pathology.

Anti-cyclic citrullinated peptide antibodies in psoriatic arthritis--cross-sectional study and literature review.

RATIONALE: Anti-CCP antibodies are detectable not only in rheumatoid arthritis (RA), but also in psoriatic arthritis (PsA). It is possible those anti-CCP antibodies are associated with features of PsA and that these auto-antibodies are useful in distinguishing PsA from RA. OBJECTIVE: to evaluate the prevalence and the associations of anti-CCP antibodies in PsA patients; to evaluate the usefulness of anti-CCP antibodies in distinguishing PsA from RA. METHODS AND RESULTS: The inquiry was designed as a cross-sectional study of 41 PsA patients, 139 RA patients and 147 normal subjects, which recorded demographic data, disease activity and serology: rheumatoid factor (RF), anti-CCP antibodies. Five PsA patients (12.2%) were anti-CCP positive. Compared to anti-CCP negative PsA patients, anti-CCP positive PsA patients had a more frequently a polyarticular disease pattern (p = 0.005), they were more frequently treated with biologics (p = 0.015) and less frequently with classic disease-modifying drugs (p < 0.001). An optimal positive cutoff value for anti-CCP titer was determined (11.6 U/mL), over which it is highly probable that a known PsA patient actually has RA and psoriasis. DISCUSSION: The more aggressive the disease of anti-CCP positive PsA patients indicates the need of a more intensive management regarding anti-rheumatic treatment and follow-up. Anti-CCP antibodies can be a useful tool in differentiating PsA from RA, especially in RA-like forms of PsA, which present no elements pertaining to spondyloarthropathies.

Ultrasound in rheumatoid arthritis: volar versus dorsal synovitis evaluation and scoring.

BACKGROUND: Assessment of synovitis in rheumatoid arthritis (RA) is a major issue for a proper treatment administration; it has been proven that ultrasound (US) examination could be of valuable help and it is currently being investigated as a possible outcome measure for the disease. It is, though, of greatest importance to accurately establish the place of US scores among the already validated outcome measures, according to Outcome Measures for Rheumatoid Arthritis in Clinical Trials (OMERACT) filter. The present study is designed to compare the results of gray-scale ultrasound (GSUS) and Power Doppler ultrasound (PDUS) additive scores, separately calculated for volar and dorsal aspects of the hand, with physical examination, patient's evaluation of disease pain and global activity on Visual Analogic Scale (VAS) and traditional scores for disease activity assessment (DAS28, CDAI, SDAI, HAQ). The final aim is to prove the advantages of volar US evaluation in RA patients. METHODS: 42 RA patients have been clinically evaluated for pain and swelling of their hand joints, completed VAS and HAQ questionnaires and underwent both volar and dorsal sonography of the hands during the same day. The US examiner was blinded to clinical assessments and lab results. For each patient 20 joints were assessed by sonography (radiocarpal, intercarpal, metacarpophalangeal (MCP) 2-5, proximal interphalangeal (PIP) 2-5). Carpal joints were only evaluated from dorsal view, while MCPs and PIPs were evaluated both from dorsal and volar aspect resulting a total of 36 distinct evaluations for each patient. GSUS synovial hypertrophy was assessed both by quantitative measurement and semiquantitative scale (0-3 grades); Doppler signal (PDUS) was recorded on a semiquantitative scale (0-3 grades). The semiquantitative grades for both GSUS and PDUS evaluation of each joint were added and the sum was defined as the Echographic Score (ES) of each patient. Separately, we added the semiquantitative grades for volar and dorsal side, resulting in Volar ES (VES) and Dorsal ES (DES) of each patient. RESULTS: We found ESs correlated with other activity scores: DAS28, CDAI, SDAI, HAQ. Correlations with clinical indices as CDAI and SDAI were stronger for VES than for DES. US discovered more synovitis than clinical examination. CONCLUSION: VES is a suitable reflection of RA activity and volar US examination should accompany the dorsal one both in clinical practice and in clinical trials.

Neuromyelitis optica--complication or comorbidity in primary Sjögren's syndrome?

We report two cases of neuromyelitis optica (NMO) associated with primary Sjögren's syndrome (pSS), comparing the clinical and laboratory features of these predominant neurological patients and reporting their different outcome. NMO - a severe demyelinating disorder of the central nervous system - primarily affects the spinal cord and optic nerves, resulting in longitudinally extensive transverse myelitis and/or optic neuritis. Our patients had a late pSS diagnosis, due to the absence of sicca syndrome and specific Sjögren serology in the early stages of their diseases, when the neurological symptoms prevailed. Many NMO patients have an accompanying autoimmune disease, most commonly Sjögren syndrome and systemic lupus erythematosus or a related profile of non-organ-specific autoantibodies. Neurologic involvement occurs in approximately 20% of patients with pSS, usually preceding the diagnosis (in 75-80% of the cases) [1,2]. The frequency of both neurologic manifestations (revealing pSS) and negative autoimmune serology, especially in the event of CNS involvement, could explain why underlying pSS is misdiagnosed [3,4]. Screening for pSS should be systematically performed in cases of acute or chronic myelopathy and/or cranial nerve involvement, mainly because these patients have a severe outcome. The presence of the anti-aquaporin4 antibodies, besides anti-Ro and anti-La, in both reported cases, is intriguing and raises the question of whether we are facing two distinct diseases or the NMO is just complicating an unusually less expressive Sjögren's syndrome subtype.

Treatment of extrahepatic manifestations of chronic hepatitis C viral infection--a challenge.

Often, chronic hepatitis C infection is clinically manifested as extra hepatic disease. Therapy of the extra hepatic manifestations (EHM) is always difficult and based on the optimal and individual association of antiviral treatment, immunosuppressant and plasma cleaning techniques. We observed for 4 years 246 patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were diagnosed as chronic C hepatitis. 130 of those patients have had at least one EHM. In our experience, the presence of an EHM is significantly correlated with lack of early viral response and sustained viral response, as well. Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy associated to plasmapheresis. When present, peripheral neuropathy and cryocrit greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Long-term outcomes of office-based buprenorphine/naloxone maintenance therapy.

BACKGROUND: Buprenorphine/naloxone was approved by the FDA for office-based opioid maintenance therapy (OMT), with little long-term follow-up data from actual office-based practice. 18-Month outcome data on the office-based use of buprenorphine/naloxone (bup/nx) and the impact of socioeconomic status and other patient characteristics on the duration and clinical effects of bup/nx are reported. METHODS: This retrospective chart review and cross-sectional telephone interview provide treatment retention of opioid-dependent patients receiving bup/nx-OMT in an office-based setting. 176 opioid-dependent patients from two different socioeconomic groups (high and low SES) were begun on bup/nx, started intensive outpatient treatment, and followed-up after a minimum of 18 months (18-42 months) by telephone interview to assess treatment outcome. RESULTS: 110 subjects (67%) completed the interview, 77% remained on bup/nx with no difference in retention between high and low SES groups. Those on bup/nx at follow-up were more likely to report abstinence, to be affiliated with 12-step recovery, to be employed and to have improved functional status. CONCLUSIONS: Bup/nx-OMT is a viable treatment option and when coupled with a required abstinence oriented addiction counseling program is effective in promoting abstinence, self-help group attendance, occupational stability, and improved psychosocial outcomes in both low SES and high SES patient populations over an 18-42-month period.