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.

OARSI guidelines for the non-surgical management of knee osteoarthritis.

OBJECTIVE: To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide. METHOD: Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores. RESULTS: Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). CONCLUSION: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.

A clinical predictive score for mood disorder risk in low-income primary care settings.

BACKGROUND: Despite availability of validated screening tests for mood disorders, busy general practitioners (GPs) often lack the time to use them routinely. This study aimed to develop a simplified clinical predictive score to help screen for presence of current mood disorder in low-income primary care settings. METHODS: In a cross-sectional study, 197 patients seen at 10 primary care centers in Santiago, Chile completed self-administered screening tools for mood disorders: the Patient Health questionnaire (PHQ-9) and the Mood Disorder Questionnaire (MDQ). To determine participants' current-point mood disorder status, trained clinicians applied a gold-standard diagnostic interview (SCID-I). A simplified clinical predictive model (CM) was developed based on clinical features and selected questions from the screening tools. Using CM, a clinical predictive score (PS) was developed. Full PHQ-9 and GP assessment were compared with PS. RESULTS: Using multivariate logistic regression, clinical and demographic variables predictive of current mood disorder were identified for a simplified 8-point predictive score (PS). PS had better discrimination than GP assessment (auROC-statistic=0.80 [95% CI 0.72, 0.85] vs. 0.58 [95% CI 0.52, 0.62] p-value <0.0001), but not as good as the full PHQ-9 (0.89 [95% CI 0.85, 0.93], p-value=0.03). Compared with GP assessment, PS increased sensitivity by 50% at a fixed specificity of 90%. Administered in a typical primary care clinical population, it correctly predicted almost 80% of cases. LIMITATIONS: Further research must verify external validity of the PS. CONCLUSION: An easily administered clinical predictive score determined, with reasonable accuracy, the current risk of mood disorders in low-income primary care settings.

Inter and intra-estuary variability in ingress, condition and settlement of the American eel Anguilla rostrata: implications for estimating and understanding recruitment.

The objective of this study was to quantify spatial and temporal variability of anguillid glass eel ingress within and between adjacent watersheds in order to help illuminate the mechanisms moderating annual recruitment. Because single fixed locations are often used to assess annual recruitment, the intra-annual dynamics of ingress across multiple sites often remains unresolved. To address this question, plankton nets and eel collectors were deployed weekly to synoptically quantify early stage Anguilla rostrata abundance at 12 sites across two New Jersey estuaries over an ingress season. Numbers of early-stage glass eels collected at the inlet mouths were moderately variable within and between estuaries over time and showed evidence for weak lunar phase and water temperature correlations. The relative condition of glass eels, although highly variable, declined significantly over the ingress season and indicated a tendency for lower condition A. rostrata to colonize sites in the lower estuary. Accumulations of glass eels and early-stage elvers retrieved from collectors (one to >1500 A. rostrata per collector) at lower estuary sites were highly variable over time, producing only weak correlations between estuaries. By way of contrast, development into late-stage elvers, coupled with the large-scale colonization of up-river sites, was highly synchronized between and within estuaries and contingent on water temperatures reaching c. 10-12 degrees C. Averaged over the ingress season, abundance estimates were remarkably consistent between paired sites across estuaries, indicating a low degree of interestuary variability. Within an estuary, however, abundance estimates varied considerably depending on location. These results and methodology have important implications for the planning and interpretation of early-stage anguillid eel surveys as well as the understanding of the dynamic nature of ingress and the spatial scales over which recruitment varies.

Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia.

OBJECTIVE: To determine the feasibility of using the Medication Event Monitoring System (MEMS) to estimate medication compliance in patients with schizophrenia or schizoaffective disorder. SUBJECTS AND SETTING: Fourteen of 35 consecutive patients admitted to a psychiatric inpatient hospital with schizophrenia or schizoaffective disorder who met eligibility requirements and gave informed consent. INTERVENTION: After random assignment to either risperidone or typical antipsychotic treatment, medication upon discharge from hospital was dispensed in a bottle with a MEMS cap which recorded the number of bottle openings and the date and time of each opening. The first 6 patients were asked to return monthly for data downloading. The next 8 were asked to return weekly during the first month and every 2 weeks thereafter; they were also paid $5 for returning each bottle. OUTCOME MEASURES: MEMS data collected over a 6-month period and hospital readmission data. RESULTS: Patient medication compliance data were collected from 10 (71%) of 14 patients during the first month, from 7 (58%) of 12 (2 patients dropped out) during the second and from 5 (45%) of 11 (a third patient dropped out) during months 3-6. Mean compliance rates were 63% for the first month and ranged from 56% to 45% over the next 5. First-month compliance rates were significantly lower for those who were subsequently readmitted to hospital (n = 7) than for those who were not (p < 0.01). CONCLUSIONS: Electronic monitoring devices can be used to estimate compliance with medication regimens in patients with severe schizophrenic disorders, but there are methodological improvements that can be made to increase data recovery and compliance, and these are discussed.

Do superconductors have zero resistance in a magnetic field?

We show that dc voltage versus current measurements of a YBa(2)Cu(3)O(7-delta) film in a magnetic field can be collapsed onto scaling functions proposed by Fisher et al. [Phys. Rev. B 43, 130 (1991)] as is widely reported in the literature. We find, however, that good data collapse is achieved for a wide range of critical exponents and temperatures. These results strongly suggest that agreement with scaling alone does not prove the existence of a phase transition. We propose a criterion to determine if the data collapse is valid, and thus if a phase transition occurs. To our knowledge, none of the data reported in the literature meet our criterion.

Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents.

Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with Ki values < 5 microM are described). The most effective inhibitor studied was compound 12 with a Ki value of 0.151 microM. Six of the compounds described are also effective trypanocides with IC50 values < 1 microM.

Notes from the field--an adventure in multiculturalism.

M.C. Sullivan was formerly the Executive Vice President of Midwest Bioethics Center. During her tenure at MBC, she was awarded a Kornfeld Foundation fellowship to pursue fieldwork in multicultural healthcare ethics. This article reports on her project, which involved travel in Europe, Asia, Central and North America, and the Caribbean, to experience indigenous culture, and to learn, in the United States, from established agencies serving immigrant populations. The research was not conducted scientifically. The methods and findings are anecdotal and attributable only to the author.

Longitudinal neurologic follow-up in neonatal intensive care unit survivors with various neonatal morbidities.

OBJECTIVE: The purpose of this prospective longitudinal study was to examine neurocognitive and school performance outcomes of low birth weight infants with reference to neonatal morbidity and socioeconomic status. We further evaluated the cognition and school performance based on their neurologic status at the time of assessment. METHODS: One hundred eighty-eight children (39 healthy full-term and 149 preterm infants) were classified into 4 subgroups based on their neonatal medical status: healthy, sick (without neurologic complications), small for gestational age, and neurologically compromised infants. Neurologic status was classified as normal, suspect, or abnormal at hospital discharge, 18 months, 30 months, 4 years, and 8 years of age. Socioeconomic status, cognitive, and school performances were assessed. RESULTS: Neurologically, both full-term and healthy preterm groups did well during the 8-year period. There were significant fluctuations between suspect and abnormal neurologic classifications among the 3 preterm groups with neonatal complications. Preterms with neurologic abnormality during the neonatal period did the poorest with 45% of the group remaining abnormal at 8 years of age. Children who were neurologically normal had higher cognitive scores at ages 4 and 8 than those categorized as suspect or abnormal. Preterm infants with neurologic abnormality required significantly more academic resources in the school. Reading and math achievement scores were the lowest for the preterm groups classified as neurologically suspect or abnormal. CONCLUSIONS: Neonatal morbidities exert a significant impact in neurologic outcomes among preterm children during the 8 years of assessment. Compromised neurologic status adversely affects cognitive and school performances. Neonatal medical status is an important variable indicating neurocognitive and school performance outcomes in low birth weight infants.

Medical and ecological factors in estimating motor outcomes of preschool children.

The twofold purpose of this study was to compare motor function in preschool children born with varying degrees of medical risk and to determine the independent contribution to motor function of three domains of ecological influence. One hundred and eighty-four 4-year-old children and their mothers participated. Three predictor sets, proximal, distal, and child, and four motor outcomes were measured by multiple methods. Children born prematurely scored lower on all dimensions of motor function. Prematurity complications had a different effect on motor function. Hierarchical regression models explained 16-40% of motor score variance. Results are discussed in relation to heterogeneity of prematurity and ecological influences on motor outcomes.

Proximal and distal correlates of maternal control style.

Control, as an aspect of maternal interaction, has been found to be an important component to optimal child development. Maternal control style is defined as a mother's tendency to be controlling or supportive of her child's autonomy. The relationship between two types of maternal characteristics, proximal and distal, and maternal control style was investigated in a sample of 184 mothers and their 4-year-old children. Global ratings of videotaped data of two problem-solving tasks were made on a 5-point scale. An optimal maternal control style was associated with higher levels of the distal maternal characteristics of maternal education, age, occupation, and higher levels of the proximal characteristics of maternal responsivity and involvement. A hierarchical regression model explaining 26% of the variance in maternal control style scores supports the importance of both types of maternal characteristics. The results are discussed in relation to the methodology and the theoretical framework of role.

The PATHWAYS Hospital Project.

In 1995, the Hospital Ethics Committee Consortium organized by Midwest Bioethics Center created the PATHWAYS to Patient-Centered Palliative Care: A Community Approach--a guideline document, or "how to" manual for hospitals that want to improve care of the seriously ill and dying. Following the publication and wide dissemination of this manual, the Center began to implement strategies to produce positive change in the way hospitals respond to dying persons and their families. Spurred by the same desire to alter hospital culture through improved care of the dying, eleven hospitals collaborated with the Center to form the PATHWAYS Hospital Project.

Lessons from the field--health care experiences and preferences in a Latino community.

As part of Midwest Bioethics Center's PATHWAYS to Improve End-of-Life Care project, we conducted an exploratory study in the Latino community of Kansas City to understand health beliefs, practices, and values, particularly as they relate to end-of-life care. We conducted ten focus groups and interviewed more than seventeen individuals who serve the Latino community in a social service, ministry, or health care capacity. We found that people were very concerned with "barriers to health care" (our term), and very willing to reveal their preferences for health care decision making and end-of-life care treatment options. We believe that bioethicists should conduct other, similar projects because they can improve our engagement with the Latino population and help Latinos find a greater voice in health care settings.

Maternal interaction patterns and preschool competence in high-risk children.

BACKGROUND: The influence of specific maternal interaction patterns as compensatory mechanisms in promoting development of medically high-risk children has been understudied. OBJECTIVES: To investigate the association of three maternal interaction patterns, maternal responsivity, involvement, and control style, with preschool competency in a medically heterogeneous sample. METHOD: Children (N= 184) and their mothers participating in a prospective longitudinal study were assessed in a laboratory protocol and home visit. The methods of measurement were maternal self-report, global rating scales, interview, and nationally standardized instruments. RESULTS: Evidence of a maternal compensatory mechanism was exhibited in mothers' higher involvement with their children who were born at high medical risk (F(1,183) = 6.26, p = .01). Mothers of the most competent children demonstrated higher maternal responsivity, involvement, and more appropriate control than mothers of children who were not as competent. In hierarchical regression models, the three maternal interaction patterns were significant predictors after perinatal risk and maternal education were controlled explaining 29-37% of the variance in child competence scores. CONCLUSION: These findings imply that differential child outcomes are associated with specific maternal interaction patterns. It suggests that a combination of diverse information revealed in specific maternal interaction pattern is needed to predict cognitive, linguistic, and problem-solving competencies. Future research should consider individual differences in mother-child interaction patterns in order to isolate their significance for optimal child development.

Abnormal development of biceps brachii phasic stretch reflex and persistence of short latency heteronymous reflexes from biceps to triceps brachii in spastic cerebral palsy.

Co-contraction of antagonist muscles is characteristic of spasticity arising from perinatal brain damage but not in spasticity occurring after brain damage in adulthood. Such co-contraction is a normal feature of early post-natal motor development. Heteronymous, monosynaptic Group Ia projections from biceps brachii to both the antagonist triceps brachii and to other synergist and non-synergist muscles of the upper limb occur in the newborn baby and become restricted during the first 4 years to motor neurons of primarily synergistic muscles. Longitudinal and cross-sectional studies have been performed to test the hypothesis that inappropriate heteronymous excitatory projections persist in children with perinatal brain damage who develop spasticity. Subjects with spasticity, from brain damage acquired in adulthood were also studied to determine if these projections simply become unmasked as part of spasticity, independent of the age of occurrence of the brain damage. Twenty-nine healthy newborn babies and 29 at high risk for cerebral palsy, 12 of whom developed spastic quadriparesis, were studied longitudinally for 4 years. Thirty-eight subjects, aged 8-30 years, with spasticity of perinatal origin (11 hemiplegic, 11 quadriplegic, 16 with Rett syndrome) and 11 subjects with stroke in adulthood and spastic hemiplegia were also studied. The results were compared with those obtained in 372 normal subjects aged from birth to 55 years. Small taps were delivered to the tendon of biceps brachii using an electromechanical tapper. Surface EMG was recorded from biceps and triceps brachii, pectoralis major and deltoid. In the longitudinal study, those developing spastic quadriparesis showed persistent low thresholds for the homonymous phasic stretch reflex, which had abnormally short onset latencies. There was persistence of short onset heteronymous excitatory responses in triceps brachii, while a normal pattern of restriction of heteronymous responses to pectoralis major and deltoid occurred. The same pattern was observed in older subject groups with spasticity of perinatal origin. In adults with hemiplegia following stroke the threshold of the homonymous phasic stretch reflex was low, but it had a normal onset latency. There was no evidence of abnormal heteronymous excitatory responses. In conclusion, exaggerated excitatory responses to primary muscle afferent input were observed in the homonymous (biceps brachii) and antagonist (triceps brachii) motor neurons in subjects with spasticity arising from perinatal brain damage. They are likely to play an important role in the predominant co-contraction of agonist/antagonist muscles during voluntary movement observed in subjects with spastic cerebral palsy.

Thoughts on the clinician's response to health care reform: a cautionary note.

In the course of contemporary health care discussion, we frequently refer to "health care reform" and its effect on health care delivery. The context within which we use the expression somehow manages to convey the idea that there is some kind of discreet "fait accompli" to which we can point. This basic premise is incorrect and ascribing to it renders much of the discussion about it in error.