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.     

Certolizumab pegol for the treatment of psoriasis

Introduction: Psoriasis is a chronic immunomediated and inflammatory disease involving mainly skin and joints, often associated with several metabolic and non-metabolic comorbidities. TNF-alpha inhibitors have shown long-term efficacy and safety/tolerability in psoriasis, and preliminary data support the use of certolizumab pegol (CZP) as well.

Areas covered: The authors review the pharmacological properties of CZP, as well as its safety data and efficacy profile. They also review the quality of life outcomes related to CZP in psoriasis. The authors also provide their expert opinion on the subject.

Expert opinion: CZP is a promising treatment for psoriasis owing to its rapid reduction of disease activity, long-term therapeutic efficacy – both in bio-naive and non-bio-naive patients, long term safety and low rate of site injection reactions. CZP seems to be a promising therapeutic option for psoriasis patients, although further evidence supporting the continuing clinical program for development of CZP in psoriasis is needed.     

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.     

Pharmacokinetic and pharmacodynamic changes in older adults and implications for palliative care

Background: As the population of older adults continues to increase, there will be an increase in the number of older patients requiring pain and symptom management in the setting of advanced, serious illness.

Objectives: To review age-related changes in pharmacokinetics and pharmacodynamics, and to put these changes in the context of providing palliative care to geriatric patients.

Method: Review of literature relevant to age-related changes in physiology, pharmacokinetics, and pharmacodynamics; and the practice of palliative care for geriatric patients.

Results: Multiple age related changes occur which affect the choice and dosing of medications, including those used for pain and symptom management.

Conclusion: The safe and effective management of symptoms in advanced illness for older adults depends on having a clear understanding of physical and metabolic changes and their impact of selection of drug therapy.     

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.     

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.     

Effect of anti IL-12/23 on body composition: results of bioelectrical impedance analysis in Caucasian psoriatic patients

Background: Bioelectrical impedance analysis (BIA) is an inexpensive, non-invasive and fast method to assess body composition. Little is known of the interaction between anti IL 12/23 treatment and body composition. The aim of this study was to evaluate 6- and 12-month changes in body weight, Body Mass Index (BMI) and body composition assessed by BIA in psoriatic patients treated with anti-IL-12/23.

Research design and methods: Demographic and clinical data were collected for each enrolled patient. Physical examination, anthropometric assessment, Psoriasis Area and Severity Index (PASI) assessment and body composition by BIA (single-frequency 50 kHz), were assessed at baseline and at 6 and 12 months of treatment.

Results: A significant decrease in body weight, compared to baseline, in BMI, Fat Mass at month 6 and a significant increase at month 12 for body cellular mass (BCM) and Phase Angle (PhA) were observed. In addition, a significant increase was found for intracellular water.

Conclusion: At baseline, psoriatic patients showed a lower BCM and a lower mean PhA score. During ustekinumab treatment, the mean PhA and BCM scores increased with an improvement in psoriatic disease. Thus, ustekinumab can be an effective drug for improving not only psoriasis but also the general clinical status of patients.     

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.     

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

     

A double-blind placebo-controlled clinical investigation into pain reduction effect of placing the pain spot outside the intersection area of the two currents of interferential therapy compared to traditional method

Background: Interferential therapy (IFT) is applied to intersect in the painful area but no confirmed effect with this method. Experimentally, the highest voltage of IFT is induced outside the intersection of the two currents. Placing the painful area outside the intersection point (external application) would reveal a better effect.

Objectives: To examine the effect of external application in pain compared to traditional method.

Design: A double-blind placebo-controlled clinical investigation.

Setting: A public hospital.

Participants: 168 LBP subjects.

Interventions: Assignment: (1) external IFT, (2) placebo external IFT, (3) traditional IFT and (4) placebo traditional IFT. Groups 1 and 3 received 20 min of IFT at 100 Hz and groups 2 and 4 received sham IFT.

Main outcome measures: Before and after IFT session, pain severity (VAS), pressure threshold (PPT), pain distribution and ROM were assessed.

Results: IFT changed all outcomes similarly. VAS and ROM improved statistically, P < 0.03. A trend of better VAS reduced with active IFTs.

Conclusions: No therapeutic difference between the two methods.     

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.     

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.

     

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.     

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.     

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.     

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.     

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.