Comparative functional and pharmacological characterization of Sandoz proposed biosimilar adalimumab (GP2017): rationale for extrapolation across indications

Background: Biosimilars are approved biologics that match reference medicine in quality, safety, and efficacy. The development of Sandoz proposed biosimilar adalimumab (SPBA; GP2017) involved a target-directed, iterative state-of-the-art quality-by-design development program. Here, we describe the functional and pharmacological characterization of SPBA and its proposed mechanism of action in immune-mediated inflammatory diseases.

Methods: Sensitive in vitro binding and functional characterization studies, and nonclinical evaluations (pharmacokinetics, pharmacodynamics, and safety/toxicology) were performed as part of a stepwise approach to confirm the biosimilarity of SPBA with reference adalimumab.

Results: Matching values were reported for SPBA and reference adalimumab in binding assays involving tumor necrosis factor (TNF)-α, complement 1q and human immune effector cell Fcγ receptor subtypes in cell-based bioassays for Fc receptor function (complement- and antibody-dependent cytotoxicity), and in apoptosis inhibition. Furthermore, SPBA and reference adalimumab were equivalent in terms of membrane TNF binding and induction of reverse signaling. Pharmacokinetics of SPBA and reference adalimumab were comparable in rabbits, and the two biologics were equally effective in a human TNF transgenic mouse model of polyarthritis.

Conclusion: SPBA matches reference adalimumab with regards to target binding, functional, pharmacokinetic, and pharmacodynamic properties at the nonclinical level supporting its approval in all indications of the reference adalimumab.     

An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly

Introduction: Psoriasis in elderly patients is considered to be of emerging clinical relevance because of the increase in the aged segment of the population. Psoriasis in such a group raises significant management challenges. There is an age-related immunosuppression, a high frequency of comorbidities, and polypharmacy, which enhances the potential risk of drug interactions or side effects when an additional systemic treatment must be administered. Despite the aging of the general population, clinical studies focusing on treatment of geriatric psoriasis are limited. Patients > 65 years are often not included in randomized clinical trials. As a result, the geriatric population affected by moderate-to-severe psoriasis is usually under-treated.

Areas covered: This review focuses on the use of systemic treatments in elderly psoriatic patients and their efficacy and safety data, analyzing the available literature evidences.

Expert opinion: Conventional agents should be carefully evaluated in each patient considering the possible organ impairment, comorbidities, concomitant medications and contraindications. Apremilast is an appropriate treatment for elderly patients. Biologics represent a safe option for a long-term management of psoriasis. Etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and brodalumab have not been associated to a higher risk of adverse events in the elderly.     

The effect on the patient flow in a local health care after implementing reverse triage in a primary care emergency department: a longitudinal follow-up study

Objective: Reverse triage means that patients who are not considered to be in need of medical services are not placed on the doctor’s list in an emergency department (ED) but are sent, after face-to-face evaluation by a triage nurse, to a more appropriate health care unit. It is not known how an abrupt application of such reverse triage in a combined primary care ED alters the demand for doctors’ services in collaborative parts of the health care system.

Design: An observational study.

Setting: Register-based retrospective quasi-experimental longitudinal follow-up study based on a before–after setting in a Finnish city.

Subjects: Patients who consulted different doctors in a local health care unit.

Main outcome measures: Numbers of monthly visits to different doctor groups in public and private primary care, and numbers of monthly referrals to secondary care ED from different sources of primary care were recorded before and after abrupt implementation of the reverse triage.

Results: The beginning of reverse triage decreased the number of patient visits to a primary ED doctor without increasing mortality. Simultaneously, there was an increase in doctor visits in the adjacent secondary care ED and local private sector. The number of patients who came to secondary care ED without a referral or with a referral from the private sector increased.

Conclusions: The data suggested that the reverse triage causes redistribution of the use of doctors’ services rather than a true decrease in the use of these services.     

Factors associated with self-rated health in primary care

Background: Self-rated health (SRH) measures one’s current general health and is a widely used health indicator. Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships are suspected to influence SRH, but studies in primary health care settings are sparse.

Objective: To examine the associations between patients’ self-rated health and their sleep problems, somatic health complaints, and unmet needs in interpersonal relationships.

Design: We collected data via questionnaires for this cross-sectional study from general practice.

Setting: Primary health care in Norway.

Subjects: 1302 consecutive patients participated.

Main outcome measures: The questionnaire included a single question about SRH, the Bergen Insomnia Scale (BIS), five questions on somatic health complaints, and three questions from the Basic Psychological Needs Scale (BPNS) pertaining to the relationships domain. We analyzed our data using ordinal logistic regression models.

Results: Our response rate was 74%. The prevalence of fair/poor SRH was 26%, with no gender differences. We revealed a significant association between increasing age and reduced SRH. The study showed that sleep problems and somatic health complaints were strongly associated with SRH, and unmet needs in relationships were also significantly and independently associated with reduced SRH in a full model analysis.

Conclusion: Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH. These factors are all modifiable and could be managed both within and outside a primary care setting in order to improve SRH.

• Key Points

• There was a high prevalence of reduced SRH in clinical general practice

• Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH

• These predictors are all modifiable with a potential to improve SRH

     

Use of panel testing for detection of antinuclear antibody in a resource-limited setting: an appraisal

Objectives: Despite an increase in the incidence of systemic connective tissue diseases (CTD), panel testing for detection of antinuclear antibodies (ANA) is not a routine practice in many health centers of the Indian subcontinent. Consequently, the data on its significance is scanty.

Methods: To evaluate utility of panel testing, line immunoassay (LIA) and indirect immunofluorescence antinuclear antibody test (IIF-ANA) were performed in 321 cases of CTD.

Results: Out of 321 serum samples screened by the above tests, 227 were positive and 18 were negative by both LIA and IIF-ANA. Additional 11/321 (3.4%) cases were picked up by LIA. SSA was most common specificity in these cases followed by SSA/SSB, SSB, Ro-52, Jo-1, dsDNA and nRNP/Sm.

Conclusion: Use of LIA along with IF-ANA and ELISA improves sensitivity of CTD screening.     

A systematic review to determine the optimal type and dosage of land-based exercises for treating knee osteoarthritis

Background: Exercise has been acknowledged as an effective non-pharmacological intervention for osteoarthritis. Consensus regarding the type of exercise i.e., aerobic or resistance, weight bearing or non-weight bearing, and dosage i.e., frequency, loading, duration, or intensity, is yet to be reached.

Objective: The purpose of this review was to address two questions: (1) is there a difference in clinical outcomes between different exercise programmes; and (2) what is the optimal dosage of exercises for people with knee osteoarthritis.

Methods: A systematic review was conducted. A study of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, and the Cochrane Library) and unpublished literature (WHO International Clinical Trials Registry Platform, current controlled trials and the United States National Institute of Health Trials Registry, and Open Grey) was undertaken in January 2013. Studies assessing the clinical outcomes of different types and dosages of exercise for people with osteoarthritis of the knee were included. Methodological quality was assessed using the critical appraisal skills programme (CASP) randomized controlled trial (RCT) appraisal tool.

Results: Ten studies assessing 958 knees from 916 participants were included. Exercise significantly improved pain and function for people with knee osteoarthritis. There was no significant difference in outcomes for different types of exercise i.e., aerobic versus resistance, weight bearing versus non-weight bearing. There was no significant difference in respect to the intensity of exercise i.e., high- versus lower-intensity resistance or aerobic exercises. The quality of the literature was moderate to high.

Conclusions: While exercise appears to improve symptoms and optimize function for people with knee osteoarthritis, the optimal form and dosage of exercise remains unknown.

Funding: None.

PROSPERO Registration Number: CRD42012002811.     

Does an exercise programme integrating the Nintendo Wii-Fit Balance Board improve balance in ambulatory children with cerebral palsy?

Background: Cerebral palsy is a common childhood movement disorder with balance impairment a common complaint. Active video games such as the Nintendo Wii-Fit have been found to be a valuable therapeutic tool, enjoyed by a variety of populations including children with CP, but a synthesis of the research investigating its specific use for balance in children with CP has yet to be conducted.

Objectives: To determine the effectiveness of a Nintendo Wii-Fit Balance board programme in improving balance in ambulatory children with CP.

Methods: A systematic search of the literature was conducted. A total of six studies matching inclusion and exclusion criteria were found and critically appraised by a modified version of Downs and Black's Checklist.

Results: All studies used the Nintendo Wii-Fit software, with variable programme length and frequency of sessions. All but one study demonstrated a significant improvement in at least one balance outcome post-intervention, with dynamic balance appearing to be greater influenced.

Discussion: The impact of age on the results was inconclusive. Children with cognitive, visual or vestibular impairments may show less of an improvement. A 6-week programme appears sufficient, provided training frequency remains high. Overall, there is moderate evidence to suggest that a Nintendo Wii-Fit Balance Board programme can improve balance in children with CP.

Conclusions: Balance training with a Nintendo Wii-Fit Balance Board can enhance balance in individuals with ambulatory CP. Due to limited evidence investigating ataxic or dyskinetic CP, results from this study should be generalised with caution to these subtypes. Future research should aim to investigate the long-term effects of the intervention.     

Identification of the affected ear in lateral canal benign paroxysmal positional vertigo

Background:

The effective management of lateral canal benign paroxysmal positional vertigo (LC-BPPV) is dependent upon the accurate identification of the affected ear. The supine roll test is the gold standard for diagnosing LC-BPPV. However, in some cases, the elicited nystagmus has a similar intensity when the head is rolled to the right or to the left.

Objectives:

The purpose of this systematic review was to determine the effectiveness of accessory diagnostic procedures, used in conjunction with the supine roll test, at accurately identifying the affected ear in individuals with LC-BPPV.

Methods:

The following databases were searched: (1) CINAHL Plus with Full Text, (2) ProQuest Medical Library, and (3) MEDLINE. The following search terms were used: (1) ‘lateral canal’ OR ‘horizontal canal’ AND (2) ‘positional vertigo’ OR ‘positioning vertigo’ OR ‘positional nystagmus’ OR ‘positioning nystagmus’. Evidence level was examined with the Oxford Centre for Evidence-Based Medicine 2011 levels of evidence method, and methodological rigour was examined with the QUADAS method.

Results:

A database search originally identified 1348 records, and nine studies were ultimately included in the qualitative synthesis. This systematic review revealed four index tests that, when used in conjunction with the supine roll test, were able to accurately identify the affected ear in a majority of individuals with LC-BPPV.

Conclusions:

The pseudo-spontaneous test was found to be slightly superior to the other three index tests in terms of eliciting nystagmus during its administration and identifying the same affected ear as the supine roll test.     

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series

Background: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome.

Purpose: We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers.

Methods: A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management.

Results: All 13 patients experienced symptom relief after administration of capsaicin cream.

Conclusion: Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.     

Serum osmolal gap in clinical practice: usefulness and limitations

Background: Although serum osmolal gap can be a useful diagnostic tool, clinicians are not familiar with its use in clinical practice.

Objectives: The review presents in a series of questions-answers and under a clinical point of view the current data regarding the use of osmolal gap.

Discussion: The definition and the best formula used for the calculation of osmolal gap, the main causes of increased osmolal gap with or without increased anion gap metabolic acidosis, as well as the role of concurrent lactic acidosis or ketoacidosis are presented under a clinical point of view.

Conclusions: The calculation of osmolal gap is crucial in the differential diagnosis of many patients presenting in emergency departments with possible drug or substance overdose as well as in comatose hospitalized patients.     

Effects of numerical information on intention to participate in cervical screening among women offered HPV vaccination: a randomised study

Objectives: To investigate the effects of different types of information about benefits and harms of cervical screening on intention to participate in screening among women in the first cohorts offered human papilloma virus (HPV) vaccination.

Design: Randomised survey study.

Setting: Denmark.

Subjects: A random sample of women from the birth cohorts 1993, 1994 and 1995 drawn from the general population.

Interventions: A web-based questionnaire and information intervention. We randomised potential respondents to one of the following four different information modules about benefits and harms of cervical screening: no information; non-numerical information; and two numerical information modules. Moreover, we provided HPV-vaccinated women in one of the arms with numerical information about benefits and harms in two steps: firstly, information without consideration of HPV vaccination and subsequently information conditional on HPV vaccination.

Main outcome measure: Self-reported intention to participate in cervical screening.

Results: A significantly lower proportion intended to participate in screening in the two groups of women receiving numerical information compared to controls with absolute differences of 10.5 (95% CI: 3.3–17.6) and 7.7 (95% CI: 0.4–14.9) percentage points, respectively. Among HPV-vaccinated women, we found a significantly lower intention to participate in screening after numerical information specific to vaccinated women (OR of 0.38).

Conclusions: Women are sensitive to numerical information about the benefits and harms of cervical screening. Specifically, our results suggest that HPV-vaccinated women are sensitive to information about the expected changes in benefits and harms of cervical screening after implementation of HPV vaccination.

• KEY POINTS

• Women were less likely to participate in cervical screening when they received numerical information about benefits and harms compared to non-numerical or no information.

• Specifically, numerical information about the potential impact of the reduced risk of cervical cancer among HPV-vaccinated women reduced the intention to participate among vaccinated women.

     

Content and bibliometric analyses of the Journal of Manual & Manipulative Therapy

Background:

Article characteristics and trends have been elucidated for other physical therapy-focused journals using content and bibliometric analysis. These findings are important for assessing the current state of a journal and for guiding future publication of research. To date, these analyses have not been performed for the Journal of Manual & Manipulative Therapy (JMMT).

Objective:

To describe content and trends for articles published in JMMT over a 20-year period (1993–2012).

Methods:

Journal articles were coded using previously-established domains (article type, participant type, research design, study purpose, and clinical condition). Total publications and proportion of publications based on domain were described. Articles specific to manual therapy intervention were examined and compared to data from other physical therapy-focused journals. Impact by citation and author was examined using bibliometric software.

Results:

Journal of Manual & Manipulative Therapy was found to have a recent acceleration in the number of articles published annually. Over time, topical reviews have decreased in favor of research reports. However, rigorous study designs have represented only a small portion of total journal content, and case reports have maintained a consistent publication presence. Manual therapy intervention articles in JMMT are predominantly case designs, however are similar in characteristics to manual therapy intervention articles published in other physical therapy-focused journals. For JMMT articles overall and manual therapy intervention articles across journals, young to middle-aged symptomatic adults with low back and/or neck pain were the most common study participants.

Discussion:

Increases in the number of papers and a move toward research reports were observed in JMMT over the 20-year period. Considerations for the future were outlined, including the publication of articles with more rigorous research designs. Manual therapy research for adolescents and older adults and for upper and lower extremity conditions should also be considered as priorities for the future.     

Itolizumab,a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis

Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 – dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.

Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.

Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.     

ABP 501 for the treatment of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Tumour necrosis factor α (TNF) is a cytokine with diverse cellular effects, and a key regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a TNF inhibitor.

Areas covered: In this review, we examined ABP 501, as a biosimilar candidate to adalimumab in the treatment of RA focusing on the available data. Current data indicate that ABP 501 is a highly similar alternative to adalimumab in terms of safety, efficacy, tolerability and immunogenicity. ABP 501 has already been approved by health authorities in Europe and the United States of America, as a subcutaneous (s.c.) therapy option for the treatment of patients with RA, but also for the full spectrum approved for its bio-originator adalimumab.

Expert opinion: Current body of evidence suggests that all biologic activities have been demonstrated to be equivalent between ABP 501 and the originator, including binding rates and affinity to TNF, and also the effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC). Therefore, it is fully expected to have same efficacy and safety in all indications.     

Adductor-related groin pain in the athlete

Background:

Owing to a multifactorial etiology, the differential diagnosis of groin pain in the athlete is often complex, with a diagnosis being clinically elusive in up to 30% of individuals. It has been suggested in the literature that the adductor musculature is a viable and prevalent source of groin pain. Thus, recognition of the elements related to effective management of these individuals is essential for the clinician.

Objectives:

To review the current literature related to prevalence, risk factors, clinical testing, conservative, and surgical interventions for adductor-related groin pain.

Major findings:

Adductor-related groin injuries may occur in isolation or combination. Athletes participating in multi-directional sports, with prior groin injury, weakness of adductors compared to abductors, and higher level of play are at greatest risk. Clinical testing using the adductor squeeze test at varying angles offers high specificity in the absence of imaging modalities. Evidence for preventative programs exists among soccer and ice hockey players. Interventions focusing on progressively improving adductor muscle performance and lower extremity impairments have been found effective, as have multi-modal interventions. Surgical interventions, recommended for those recalcitrant (>2 months) to conservative care appear effective, with adductor repair or tenotomy procedures being primarily described in case series designs.

Conclusion:

A paucity of research exists to determine the diagnostic utility of clinical tests as well as the efficacy of interventions. Clinicians should be aware of adductor-related groin pain as a clinical entity and recognize the potential merits and limitations of both preventive and adductor-focused interventions.     

Social disparities in diabetes care: a general population study in Denmark

Objective: We investigated the association between socioeconomic factors and the attainment of treatment goals and pharmacotherapy in patients with type 2 diabetes in Denmark.

Design: A cross-sectional population study.

Setting: The municipality of Naestved, Denmark.

Subjects: We studied 907 patients with type 2 diabetes identified from a random sample of 21,205 Danish citizens.

Main outcome measures: The proportion of patients who were not achieving goals for diabetes care based on their HbA_1c, LDL-cholesterol, blood pressure, and lifestyle, and the proportion of patients who were treated with antihypertensive and cholesterol- and glucose-lowering medication.

Methods: We investigated the association of the socioeconomic factors such as age, gender, education, occupation, income, and civil status and attainment of treatment goals and pharmacotherapy in logistic regression analyses. We investigated effect modification of cardiovascular disease and kidney disease.

Results: Middle age (40–65 years), low education level (i.e. basic schooling), and low household income (i.e. less than 21,400 € per year) were associated with nonattainment of goals for diabetes care. The association of socioeconomic factors with attainment of individual treatment goals varied. Patients with low socioeconomic status were more often obese, physically inactive, smoking, and had elevated blood pressure. Socioeconomic factors were not associated with treatment goals for hyperglycemia. Socioeconomic factors were inconsistently associated with pharmacotherapy. There was no difference in contacts to general practitioners according to SES.

Conclusions: In a country with free access to health care, the socioeconomic factors such as middle age, low education, and low income were associated with nonattainment of goals for diabetes care.

• KEY POINTS

• Middle age, low education, and low income were associated with nonattainment of goals for diabetes care, especially for lifestyle goals.

• Patients with low socioeconomic status were more often obese, physically inactive, smoking, and had elevated blood pressure.

• Association of socioeconomic factors with pharmacotherapy was inconsistent.

     

Parent-based diagnosis of ADHD is as accurate as a teacher-based diagnosis of ADHD

Objective: To review the literature evaluating the psychometric properties of parent and teacher informants relative to a gold-standard ADHD diagnosis in pediatric populations.

Method: We included studies that included both a parent and teacher informant, a gold-standard diagnosis, and diagnostic accuracy metrics. Potential confounds were evaluated. We also assessed the ‘OR’ and the ‘AND’ rules for combining informant reports.

Results: Eight articles met inclusion criteria. The diagnostic accuracy for predicting gold standard ADHD diagnoses did not differ between parents and teachers. Sample size, sample type, participant drop-out, participant age, participant gender, geographic area of the study, and date of study publication were assessed as potential confounds.

Conclusion: Parent and teachers both yielded moderate to good diagnostic accuracy for ADHD diagnoses. Parent reports were statistically indistinguishable from those of teachers. The predictive features of the ‘OR’ and ‘AND’ rules are useful in evaluating approaches to better integrating information from these informants.     

Association between continuity of care in Swedish primary care and emergency services utilisation: a population-based cross-sectional study

Objective: The primary objective of this study was to determine the association between longitudinal continuity of care (CoC) in Swedish primary care (PC) and emergency services (ES) utilisation.

Study design: A cross-sectional analysis of longitudinal population data. Setting. PC centres, out-of-hours PC facilities and emergency departments (EDs) in Blekinge County in southern Sweden. Subjects: People of all ages who lived in Blekinge County and who had made two or more visits per year to a general practitioner (GP) during office hours from 1 January 2012 to 31 December 2014.

Main outcome measure: ES utilisation.

Results: Eight-thousand one-hundred and eighty-five people were included in the study. CoC was quantified using three different indices—Usual Provider of Care index (UPC), Continuity of Care index (CoCI), and Sequential Continuity index (SECON). The CoC that the PC centres could offer their enrolled patients varied significantly between the different centres, ranging from 0.23–0.57 for UPC, 0.12–0.43 for CoCI, and 0.25–0.52 for SECON. Association between the three CoC indices and ES utilisation was computed as an incidence rate ratio which ranged between 0.50 and 0.59.

Conclusion: Longitudinal CoC was shown to have a negative association with ES utilisation. The association was significant and of a magnitude that implies clinical relevance. Computed incidence rate ratios suggest that patients with the lowest CoC had twice as many ES visits compared to patients with the highest CoC.     

Physical activity interventions for fatigue in rheumatoid arthritis: a systematic review

Background: Fatigue is a major symptom of rheumatoid arthritis (RA) and the need for effective interventions is evident. Programmes based upon physical activity (PA) have been shown to improve patient-reported fatigue in other long-term conditions.

Objectives: To investigate the effectiveness of PA interventions for reducing fatigue in adults with RA and to identify key components of effective PA interventions.

Methods: Methods were based on a previous Cochrane systematic review for non-pharmacological interventions for fatigue in RA. The following electronic databases were searched up to October 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; Social Science Citation Index; Web of Science; Dissertation Abstracts International; Current Controlled Trials Register; The National Research Register Archive; The UKCRN Portfolio Database. Randomised controlled trials evaluating PA interventions in people with RA with self-reported fatigue as an outcome measure were included.

Results: Eight studies met the inclusion criteria. Results indicated a small beneficial effect of PA on RA fatigue. The type, frequency, duration, and intensity of PA varied between studies. Delivery methods included supervised group programmes and unsupervised home exercise. Information regarding overall adherence to PA interventions was limited.

Conclusions: There is some evidence of the potential for PA to be effective in reducing symptoms of RA fatigue. However, few interventions in the included studies were designed to manage RA fatigue. These findings suggest that further work is needed to identify the optimal PA intervention for fatigue management that meets the needs of people with RA.     

The toxicity of picaridin containing insect repellent reported to the National Poison Data System

Context: While low toxicity is reported, there are sparse data on the safety of acute picaridin (icaridin) exposures in humans.

Objective: The purpose of this study was to review National Poison Data System (NPDS) data regarding ingestion of insect repellents containing picaridin and compare those to insect repellents containing DEET and other insect repellents not containing DEET.

Methods: NPDS was queried for single agent human insect repellent ingestions reported between 1 January 2000 and 31 May 2015 using the American Association of Poison Control Center generic categories 201048 (Insect Repellents with DEET) and 201049 (Insect Repellents without DEET). Picaridin-containing product exposures were assessed using Poisindex^® product ID 6744589. Insect repellents of unknown type were not included.

Results: 68,429 exposures occurred; 24% were non-DEET-containing products, of which 2% were picaridin-containing products. Among picaridin exposures, 92.9% were managed outside of a health-care facility; there were no reported cases of major effect or death, and only one case of moderate effect. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Treatment primarily included dilution/irrigation/wash.

Conclusion: Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity and was generally managed outside of a health-care facility.