IL-17 inhibition in axial spondyloarthritis: current and future perspectives

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.

Areas covered: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.

Expert opinion: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.     

Brodalumab for the treatment of plaque psoriasis: up-to-date

Introduction: Brodalumab is one of the most efficacious biologic agents available for psoriasis. It also has a unique mechanism; it is the only agent that blocks the entire interleukin 17 receptors instead of blocking individual cytokines. However, the main drawback is that brodalumab has an FDA mandated black box warning regarding suicide. This is an up-to-date article reviews the scientific validity of this issue with brodalumab and suicide.

Areas covered: A worldwide literature search was conducted on the above issue regarding suicide risk and brodalumab. All relevant articles on this topic searchable in public domain were utilized.

Expert opinion: The FDA black box warning is based on three completed suicides that happened in one research location out of 390 research sites worldwide. All three completed suicides have alternative explanations unrelated to brodalumab. The overall data from phase III clinical trials shows that psoriasis patients recorded significant improvement in depression after treatment with brodalumab. The overall impression is that the suicide issue is far from being scientifically validated and this is why the FDA itself stated in the package insert that “the cause and effect relationship these suicides and brodalumab has not been established.”     

Effectiveness and safety of secukinumab in Italian patients with psoriasis: an 84 week,multicenter, retrospective real-world study

Background: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinumab in patients with moderate-to-severe psoriasis.

Research design and methods: This 84-week, multicenter (n = 7) retrospective study analyzed data from patients who initiated and received at least 6 months of secukinumab treatment between June 2016 and June 2018 in the Campania region of Italy. Patient demographic and treatment characteristics, duration of treatment and reasons for discontinuation as well as Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores were assessed.

Results: 324 patients (63% male, mean age 50.2 years) were enrolled and received a mean 11.7 months of secukinumab treatment. Overall, 9.5% discontinued secukinumab, including 5.2% who discontinued due to secondary inefficacy and 1.8% due to adverse events. PASI, BSA and DLQI scores were significantly improved from baseline at every follow-up visit (p < 0.001) and mean PASI decreased from 15.3 ± 6.3 at baseline to 0.5 ± 1.0 at week 84. Secukinumab had comparable effectiveness in biologic naïve and non-naïve patients.

Conclusions: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis.     

Risankizumab for the treatment of moderate to severe psoriasis

Introduction: Psoriasis is a chronic inflammatory skin disorder pathogenically mediated by multiple cytokines, including interleukin (IL)-23, IL-17, and TNF. An emerging class of therapeutics that selectively blocks IL-23 has been developed. Among these new agents, risankizumab is now being investigated in phase III clinical trials, and the preliminary data are promising in inducing an excellent clinical response.

Areas covered: This review aims to describe the pathogenic role of IL-23 in psoriasis and to collect clinical data related to the efficacy and safety of risankizumab, an anti-IL-23p19 agent, in the treatment of psoriasis.

Expert opinion: Risankizumab showed high response rates in reaching complete or almost complete clearance of psoriasis. When compared to other similarly effective drugs, it may show some advantages related to its mechanism of action (direct blockade of the main pathogenic pathway), safety (no impact on the immune surveillance against Candida infection), therapeutic regimen (every-12-week injections), and effectiveness in the treatment of immune-mediated psoriasis comorbid conditions, such as psoriatic arthritis and Crohn’s disease.     

Anti-IL-17 monoclonal antibodies for the treatment of ankylosing spondylitis

Introduction: Ankylosing spondylitis is the prototype of spondyloarthritis, a chronic inflammatory disease involving mainly the axial skeleton. The treatment strategy was, until now, restricted to NSAIDs and anti-TNF agents. Targeting Interleukin 17 is an emerging option with a currently available biologic agent, secukinumab.

Areas covered: This paper reviews the available data published on secukinumab (and other anti-IL-17 agents) in ankylosing spondylitis, evaluating the effect on clinical outcomes as well as radiological progression and extra articular manifestations and safety.

Expert opinion: Secukinumab represents the first anti-IL-17A agent available for the treatment of ankylosing spondylitis, with evidence of efficacy upon signs and symptoms of the disease, even after anti-TNF failure, and acceptable safety profile.     

Biologics that inhibit the Th17 pathway and related cytokines to treat inflammatory disorders

Introduction: Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors.

Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target. In particular, the authors start by giving a brief historical excursus on biologic agent development up until the success of TNF-α inhibitors, and continue with an overview of IL12/23 pathway inhibition. Next, they describe Th17 cell biology, focusing on the role of IL-17 in host defense and in human immune-inflammatory diseases, discussing the use and side effects of IL-17 inhibitors.

Expert opinion: The IL-23/Th17 signaling pathway plays a central role in the pathogenesis of several inflammatory diseases, such as psoriasis. Recent data has demonstrated that biologics neutralizing IL-17 (ixekizumab, secukinumab) or its receptor (brodalumab) are highly effective with a positive safety profile in treating moderate to severe psoriasis, offering new treatment possibilities, especially for patients who do not respond adequately to anti-TNF-α therapies.     

Anti-interleukin-12 and anti-interleukin-23 agents in Crohn’s disease

Introduction: Blockers of IL-12/23, as well as specific blockers of IL-23, have been investigated as options for medical therapy in inflammatory bowel disease. These biological agents include ustekinumab – the first agent of this pharmacological class which has shown clinical efficacy in psoriasis, psoriatic arthritis, and moderate-to-severe Crohn’s disease (CD) – and other monoclonal antibodies under investigation, including brazikumab, risankizumab, mirikizumab, and guselkumab.

Areas covered: This review will focus on the rationale of the blockade of IL-12/23 axis in CD, efficacy and safety data of ustekinumab derived from randomized controlled trials and real-life observational studies, and the preliminary data of the highly promising selective IL-23 inhibitors.

Expert opinion: Data from literature have demonstrated that ustekinumab holds the potential to deserve a relevant role in the management of patients with CD thanks to several properties, including the fast onset of action, the long duration of efficacy, the favorable safety profile, the systemic anti-inflammatory effect, and the peculiar way of administration. Nonetheless, additional research is warranted to determine the real value of ustekinumab, as current data are not able to answer all the questions about its effectiveness in real-life practice, and the external validity of the available results is not absolute.     

The clinical toxicology of sodium hypochlorite

Introduction: Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach.

Objective: The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning.

Methods: PubMed was searched from January 1950 to June 2018 using the terms “Hypochlorite”, “Sodium Hypochlorite”, “Sodium Oxychloride”, “Hypochlorous Acid”, “Bleach”, “Chlorine Bleach”, in combination with the keywords “poisoning”, “poison”, “toxicity”, “ingestion”, “adverse effects”, “overdose”, and “intoxication”. In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant.

Epidemiology: There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012–2016.

Mechanisms of toxicity: Hypochlorite’s potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin.

Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia.

Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage.

Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns.

Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways.

Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur.

Diagnosis: The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis.

Management: Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally.

Conclusions: Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.     

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.     

Mechanisms of toxic cardiomyopathy

Background: Dilated cardiomyopathy is a frequent disease responsible for 40–50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins.

Objective: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy.

Methods: The US National Library of Medicine Pubmed database was searched from 1980 to December 2017 utilizing the combinations of the search terms “toxic cardiomyopathy”, “drugs”, “anticancer drugs”, “azidothymidine”, “rosiglitazone”, “carbon monoxide”, “alcohol”, “illicit drugs”, “cocaine”, “metamfetamine”, “metals”, “venom”. A total of 339 articles were screened and papers that dealt with the pathophysiology of toxic cardiomyopathy, either in animal models or in clinical practice were selected, with preference being given to more recently published papers, which left 92 articles.

Anticancer drugs: The mechanisms of anthracycline-induced cardiotoxicity are primarily related to their mechanisms of action as anticancer drugs, mainly the inhibition of topoisomerase II β and DNA cleavage. Additional metabolic or oxidative stress factors may play a part, together with interference with iron metabolism. The more recent drugs, trastuzumab and imatinib, also influence stress pathways.

Antiretroviral agents: Azidothymidine is cardiotoxic as a result of mitochondrial toxicity. In addition to energy depletion, azidothymidine also increases the production of mitochondrial reactive oxygen species (ROS).

Antidiabetic drugs: The cardiotoxicity of thiazolidinedione antidiabetic drugs is still under investigation, though interference with mitochondrial respiration or oxidative stress is suspected.

Cocaine: Among the multiple mechanisms involved in cocaine-related cardiotoxicity, excessive sympathetic stimulation with increased myocardial oxygen consumption is well documented in the acute form of left ventricular dysfunction. As for cocaine-related cardiomyopathy, the role of apoptosis and ROS is under investigation.

Ethanol: The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. It involves apoptosis, alterations of the excitation–contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium.

Metamfetamines: Catecholamine-mediated toxicity is the probable cause, with a possible role for genetic susceptibility.

Carbon monoxide: In addition to hypoxic injury, carbon monoxide is also directly toxic to the mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP production. There is no evidence for a delayed dilated cardiomyopathy in survivors of an acute exposure.

Metals: Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often required. Antimony may cause lethal oxidative stress and cell death mediated by elevation in intra-cellular calcium. Proposed mechanisms for mercury toxicity include glutathione depletion, production of ROS, and interruption in selenium-dependent endogenous enzymatic reactions. The existence of a lithium-induced cardiomyopathy is still debated.

Scorpion venom: Catecholamine release is the probable cause of acute cardiomyopathy following scorpion envenomation.

Conclusions: The mechanisms behind toxic cardiomyopathy are complex and multifactorial but include interference with myocardial cell bioenergetics and intracellular calcium handling, the generation of ROS, neurohormonal stress, and induction of apoptosis.     

Influence of residency training on the clinical reasoning development of Kenyan physiotherapists

Objective: The purpose of this study was to explore the clinical reasoning development of physical therapists participating in an 18-month orthopaedic residency program in Nairobi, Kenya.

Methods: A mixed methods research design was utilized. The participants’ clinical reasoning was assessed through a live patient examination prior to entering the residency program and upon graduation. One-on-one interviews were performed with the residents to explore their clinical reasoning during the final examination.

Results: Residents (n = 14) demonstrated a statistically significant improvement in their ability to perform an examination of a patient and determine a hypothetical diagnosis. The clinical reasoning process described by the participants included the hypothetical deductive and narrative reasoning models. The residents did not appear to incorporate pattern recognition during the patient assessment.

Discussion: Similar to studies on novice and expert practice in physical therapy, residents demonstrated an improvement in cue acquisition, the ability to verify and refute a hypothetical diagnosis, and the ability to match interventions to patients impairments. In addition, the residents utilized a combination of clinical reasoning models during the examination and evaluation of the patient including hypothetical deductive reasoning and narrative reasoning.

Level of Evidence: 4     

Medication adherence,biological and lifestyle risk factors in patients with myocardial infarction: a ten-year follow-up on socially differentiated cardiac rehabilitation

Objective: There is strong evidence that medication adherence and lifestyle changes are essential in patients undergoing secondary cardiovascular disease prevention. Cardiac rehabilitation (CR) increases medication adherence and improves lifestyle changes. Patients with cardiac diseases and a low educational level and patients with little social support are less responsive to improve medication adherence and to adapt lifestyle changes. The aim of the present study was to investigate the long-term effects of a socially differentiated CR intervention on medication adherence as well as changes in biological and lifestyle risk factors at two- five- and ten-year follow-up.

Design: A prospective cohort study.

Setting: The cardiac ward at Aarhus University Hospital, Denmark.

Intervention: A socially differentiated CR intervention in addition to the standard CR program.

Subjects: Patients admitted with first-episode myocardial infarction between 2000 and 2004, N?=?379. Patients were defined as socially vulnerable or non-socially vulnerable according to their educational level and extent of social network.

Main outcome measures: Primary outcome was medication adherence to antithrombotics, beta-blockers, statins and angiotensin-converting enzyme inhibitors. Secondary outcomes were biological and lifestyle risk factors defined as; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycated hemoglobin, blood pressure and smoking status.

Results: No significant long-term effect of the intervention was found.

Conclusions: The results indicate a non-significant effect of the intervention. However, it was found that equality in health was improved in the study population except concerning smoking. General practitioners manage to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.

• Key points

• The socially differentiated intervention did not significantly improve medication adherence or biological and lifestyle risk factors.

• Despite the non-significant effect of the intervention, equality in health was improved except concerning smoking.

• General practitioners managed to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.

     

Visit patterns at primary care centres and individual blood pressure level – a cross-sectional study

Objective: Hypertension is a major cause of cardiovascular disease. Nevertheless, blood pressure (BP) is often inadequately treated. We studied visit patterns at primary health care centres (PHCCs) and their relation to individual BP control.

Design and setting: Cross-sectional register-based study on all patients with hypertension who visited 188 PHCCs in a Swedish region.

Patients: A total of 88,945 patients with uncomplicated hypertension age 40–79.

Main outcome measures: Odds ratio (OR) for the individual patient to achieve the BP target of ≤140/90?mmHg.

Results: Overall, 63% of patients had BP?≤?140/90?mmHg (48% BP?<?140/90). The PHCC that the patient was enrolled at and, as part of that, more nurse visits at PHCC level was associated with BP control, adjusted OR 1,10 (95% CI 1.01 to 1.21). Patients visiting PHCCs with the highest proportion of visits with nurses had an even higher chance of achieving the BP target, OR 1.19 (95% CI 1.07 to 1.32).

Conclusions: In a Swedish population of patients with hypertension, about half do not achieve recommended treatment goals. Organisation of PHCC and team care are known as factors influencing BP control. Our results suggests that a larger focus on PHCC organisation including nurse based care could improve hypertension care.     

Nursing Consultation in a Public Bathhouse: A Community Resource for the Vulnerable Population in a European Capital

Background: In Portugal’s capital, Lisbon, there are 19 public showers (PS) attended by a vulnerable population.

Aim: To describe the assessment and interventions performed during nursing consultations.

Method: This is a quantitative, observational, and cross-sectional study.

Findings: In a convenience sample of 77 users, 52% are females, 43% are single, 52% do not possess any economic resources, 87% have mental health issues, and 32% are homeless. The main nursing focuses found were: arterial hypertension, disease management skills, and emotional suffering. The most used nursing intervention is listening, followed by the expression of feelings, valuing the individual and his/her story, analyzing causes, providing support, and comforting.

Conclusions: This study shows that the main focus of the nursing care in these facilities is the human being. The respect for individuality and dignity was the primary concern, in an attempt to empower the individual to better manage his/her health and illness processes.     

Laparoscopic anterior and posterior native tissue repair: a new pelvic floor approach

Introduction: Traditionally, a cystocele caused by a midline defect of the pelvic fascia is treated by vaginal fascia duplication, also known as anterior colporraphy. The rectocele is managed by suturing the posterior fascia and, frequently, the levator ani muscles. We developed the approach of laparoscopic anterior and posterior fascia repair by native tissue.

Material and methods: The methods were based on anterior and posterior exposure of pelvic fascia similar to the preparation of an extended sacral colpopexy. The fascia was compressed and narrowed by absorbable woven sutures, size 1. Twenty-seven patients were followed up for 6–13?months. All patients received additional apical fixation by pectopexy.

Results: In the examination group, 13 patients underwent anterior laparoscopic fascia repair and 23 had posterior repair. We detected one apical and one posterior relapse, and also one in the anterior repair group. The patient with the apical relapse reported pain and de novo urgency. Anatomical reconstruction was achieved in all other patients.

Summary: Laparoscopic anterior and posterior native tissue repair appears to be a feasible method for the treatment of midline cystocele and rectocele. No new risks were observed. The technique leaves no scar in the vagina and is well accepted.

Abbreviations: POPQ: Pelvic Organ Prolapse Quantification System; FDA: Food and Drug Association; US: United States; Fig: Figure; ICIQ: International Consultation on Incontinence Questionnaire     

Prevalence of recent fentanyl use among treated users of illicit opioids in England: based on piloted urine drug screens

Objective: To use a pilot of national fentanyl screening to establish the current prevalence of recent fentanyl use among treated users of illicit opioids in the English treatment system and inform the design of a full study.

Design: Cross-sectional fentanyl metabolite urine screening in randomly-selected study sites, stratified to cover all nine geographical regions of England, supplemented with self-report subsequent to a positive fentanyl test.

Patients: 468 adult (18 years of age and above) patients receiving treatment for opioid use disorder, screened December 2017 to May 2018.

Results: The fentanyl-positive rate in patients receiving treatment for opioid use disorder in the English treatment system was 3% (15/468, 95% CI 1.8% to 5.2%) with a per-site range (for the 10 sites in 9 regions where fentanyl was detected) of between 2% (1/57) and 15% (4/27). Self-report data indicated that the majority of fentanyl-positives (12/15, 80%) was unaware of having purchased fentanyl.

Conclusions: Despite alerts already in place, patients receiving treatment for opioid use disorder, who were fentanyl-positive, were unwittingly purchasing and consuming fentanyl.     

The effectiveness of stretching for infants with congenital muscular torticollis

Introduction: Congenital muscular torticollis (CMT) is a neck deformity that involves unilateral shortening of the sternocleidomastoid (SCM). Conservative physiotherapy management of CMT is primarily focused on stretching the affected SCM. However, there is limited research evidence on the use of stretching to improve the extensibility of SCM in infants with CMT.

Aim: To investigate the effectiveness of stretching for infants with CMT.

Method: A systematic search of AMED, CINAHL, MEDLINE, EMBASE, Physiotherapy Evidence Database (PEDro) and Cochrane Library was conducted during the period 2011–2018.

Results: Seven articles that met eligibility criteria were reviewed out of a total number of 415 articles that were screened; two articles were randomised control trials and five were cohort studies. The studies typically reported statistically significant benefits of stretching for the restoration of cervical range of movement and SCM thickness (p < 0.05). Appraisal of the studies revealed varied quality.

Conclusion: The results suggest that stretching is an effective treatment intervention for the management of infants with CMT and early physiotherapy referral can lead to decreased treatment duration. However, due to a variation in study quality; additional high-quality research is needed to help formulate more robust conclusions.     

The lived experience of Joint Hypermobility and Ehlers-Danlos Syndromes: a systematic review and thematic synthesis

Background: Joint Hypermobility Syndrome (JHS) and Ehlers-Danlos Syndrome (EDS) are heritable connective tissue disorders characterised by joint instability, pain, anxiety, depression and poor quality of life. However, peoples’ lived experiences are not well understood.

Objective: To understand the lived experiences of people with JHS and EDS.

Methods: A systematic review was conducted using PRISMA guidelines. Critical appraisal and a thematic synthesis of participants’ lived experiences were conducted. Eight online databases were searched from 1990 to February 2018: AMED, CINAHL, EMBASE, MEDLINE, PubMed, PsychINFO, SPORTDiscus and the Cochrane Library. Eligibility criteria were: (1) People with either JHS or EDS, clearly distinguished from generalised joint laxity; (2) Qualitative studies, or mixed qualitative and quantitative studies with qualitative data reported independently and (3) Published in English.

Results: A total of nine studies were included. Five main themes were identified: (1) Lack of professional understanding; (2) Restricted life; (3) Social stigma; (4) Trying to ‘keep up’ and (5) Gaining control. The implications of these results are explored.

Conclusions: Further qualitative research is required to examine the impact of JHS/EDS on a wider range of participants and in greater depth.     

Quantitative real-time PCR for differential diagnostics of parvovirus B19 infection in acute liver failure patients

Background: Human Parvovirus B19 (B19V) is a common pathogen worldwide. After primary infection, B19V-DNA may permanently persist in non-erythroid tissues, including the liver of patients with acute liver failure (ALF).

Objective: To validate a real-time PCR (qPCR) for the quantification of B19V-DNA, in order to establish a differential diagnosis for B19V infection in ALF patients.

Methods: The qPCR techniques were based on Sybr Green® and TaqMan® methodologies. To evaluate the quality parameters of both methods, samples from patients with or without B19V infection were tested. The diagnostic utility of qPCR in the detection B19V-DNA in patients with ALF was evaluated by testing archived serum and hepatic tissue explants from 10 patients.

Results: The Sybr Green® methodology showed 97% efficiency, the limits of detection and quantification were 62.6 and 53,200 copies/mL, respectively. The TaqMan® methodology showed 95% efficiency, the limits of detection and quantification were 4.48 and 310 copies/mL, respectively. A false positive result was found only with the Sybr Green® methodology. Among ALF patients without defined etiology, three (30%) were positive for B19V DNA in serum and liver.

Conclusion: The qPCR methods validated here were effective in clarifying uncommon cases of B19V-related ALF and are fit for differential diagnosis of ALF causes.