The importance of pre- and post-test counseling for prenatal cell-free DNA screening for common fetal aneuploidies

Introduction: Prenatal cell-free DNA screening for common fetal aneuploidies has rapidly changed the paradigm of prenatal care. Despite its advantages compared to conventional screening methods, its unexpectedly rapid implementation in clinical practice has generated several ethical and medical issues and misconceptions. Aggressive commercial marketing of cell-free DNA screening and media dissemination of misleading information have added confusion.

Areas covered: This review provides an extensive update and will focus on the importance of pre-and post-test counseling for prenatal cell-free DNA screening not previously discussed extensively in the available literature. Additionally, we report cell-free DNA screening implementation in the largest obstetrical tertiary unit in Finland which is one of few countries that provides all prenatal screening methods free of charge for all women and has a very high uptake of first-trimester screening. This is not a systematical review, but rather a narrative overview which includes the most relevant and recent original publications and reviews covering this issue.

Expert opinion: Despite being the most accurate method for screening of common fetal aneuploidies, the knowledge and counseling should be substantially improved. Cell-free DNA screening is not a replacement for diagnostic testing and its use in prenatal testing is complex and limited.     

Practical applications of DNA genotyping in diagnostic pathology

Introduction: Among various human tissue identity testing platforms, short tandem repeat (STR) genotyping has emerged as the most powerful and cost-effective method. Beyond forensic applications, tissue identity testing has become increasingly important in modern medical practice, in areas such as diagnostic pathology.

Areas covered: A brief overview of various molecular/genetic techniques for identity testing is provided. This includes restriction fragment length polymorphism, single nucleotide polymorphism array and STR genotyping by multiplex PCR. Diagnostic applications of STR genotyping are covered in greater details: genotyping diagnosis of gestational trophoblastic disease, resolving tissue specimen mislabeling or histologic contaminant or ‘floaters’, bone marrow engraftment/chimerism analysis and interrogation of the primary source of malignancy in patients receiving organ donation. Four clinical cases are then presented to further illustrate these important clinical applications along with discussion of the interpretation, limitations, and pitfalls of STR genotyping.

Expert commentary: STR genotyping is currently the most applicable method of identity testing and has extended its role well into the practice of diagnostic pathology with novel and powerful applications beyond forensics.     

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.     

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     

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.     

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.     

Diagnosis and treatment of pediatric pulmonary arterial hypertension

Introduction: Pediatric pulmonary arterial hypertension (PAH) remains a rare and severe disease with a poor prognosis. PAH may be idiopathic, heritable or associated with systemic conditions in particular associated with congenital heart disease.

Areas covered: A thorough and extensive diagnostic approach is required for a correct diagnosis. The outcome has improved over the last decade with a better diagnostic approach and with the initiation of new targeted therapies. However, there is still significant progress to achieve as there is still no cure for this devastating disease.

Expert opinion: Adapted clinical studies to define the best therapeutic approach are needed. Even if the treatment approach is still mainly derived from adult data and expert consensus, several studies and registries are currently underway and should deliver important information in the next future.

This review aims to give an overview of the current diagnosis and treatment strategies of PAH.     

A cross-sectional study evaluating the knowledge and beliefs about,and the use of antibiotics amongst Malaysian university students

Background: The introduction of antibiotics into modern medicine has changed clinical care by saving millions of lives. However, misuse of antibiotics has led to their benefits being overshadowed by the development of antimicrobial resistance.

Aims of Study: This study aimed to assess university students’ knowledge and beliefs about and their use of antibiotics.

Methods: This cross-sectional study was conducted among 674 medical and non-medical students of the National Defence University of Malaysia, using universal and convenience sampling methods. The data was collected using a validated questionnaire and analyzed using IBM SPSS 24, and the MANOVA test and Logistic Regression were used to explore the associated factors.

Results: More than half of the respondents’ knowledge was low and their health beliefs outdated. Age, race and program were significantly associated with up-to-date knowledge and beliefs about antibiotic use, factors associated with finishing a course of antibiotics were studying medicine, personal health, and ethnicity. The significant factors associated with antibiotic self-prescribing were beliefs having been prescribed antibiotics during the last one year, and trusting the doctors who did not prescribe antibiotics.

Conclusion: This study has identified a concerning low knowledge about antibiotics amongst some Malaysian university students, reflected in use of un-prescribed antibiotics and a lack of adherence to treatment. There is a need for educational interventions for students regarding antibiotic usage and resistance issues.     

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.     

Screening of fetal chromosomal aneuploidy diseases using noninvasive prenatal testing in twin pregnancies

Objectives: This study was aimed to report the clinical characteristics of fetal chromosomal aneuploidy diseases using noninvasive prenatal testing (NIPT) in twin pregnancies and analyze the results in terms of chorionicity, conception, and fetal fraction.

Methods: A total of 1160 women with twin pregnancies were recruited from 1 October 2015, to 1 August 2017. Next-generation sequencing technology was used to detect fetal aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and trisomy X.

Results: Aneuploidy was detected using NIPT in 26 fetuses, among which 18 fetal aneuploidies occurred in only one fetus of the twins. The rate of aneuploidy was 1.3% for dichorionic diamniotic twins and 0.5% for monochorionic diamniotic twins, respectively. The rate of aneuploidy was 1.2% for spontaneous pregnancy group and 1.1% for assisted reproductive technologies group.

Conclusion: In this study, detection of trisomy 21, trisomy 18, trisomy 13, and X abnormality in twin pregnancies was confirmed to be accurate. The aneuploidies mostly occurred in only one fetus of the twins, and trisomy 21 was the most common type. The prenatal diagnostic standard for NIPT in singleton pregnancies could perform well in twin pregnancies, which means NIPT can be popularized as routine prenatal screening in twin pregnancies.     

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.

     

Directional preference constructs for patients’ neck pain in the absence of centralization

Objectives: We conducted a secondary analysis of a prospective, observational cohort study to (1) report the prevalence of Directional Preference (DP) constructs at first examination for patients with cervical spine challenges, and (2) determine the association between DP constructs and clinical outcomes at discharge from physical therapy.

Methods: We analyzed data collected from 718 consecutive patients who presented to outpatient, private practice clinics with primary complaints of non-specific neck pain; 200 patients met the inclusion criteria and completed first examination and discharge data. Statistical analysis determined the association between DP constructs at first examination and clinical outcomes at discharge.

Results: The findings in this investigation were that (1) the most prevalent DP constructs at first examination were related to ROM and pain intensity including Patient Reported Improvement in ROM (79.5%), Increase in Spine ROM (32.5%), and Pain Intensity Change (15.0%), (2) all DP groups improved and met the MCID for disability and pain intensity change at discharge except for the group that did not exhibit Increase in Spine ROM for pain intensity, (3) no clinically significant differences in pain intensity or disability existed between DP groups at discharge, and (4) 28.5% and 6.5% of patients exhibited a relative increase in cervical spine extension and flexion ROM, respectively, post-repeated movement testing on the first examination.

Discussion: The most prevalent DP constructs at first examination were related to ROM and pain intensity, and each was associated with a comparable clinical trajectory in terms of pain and disability outcomes at discharge. The findings of this study help Mechanical Diagnosis and Therapy (MDT) providers understand the common DP constructs encountered in routine clinical practice and their relation to pain and disability outcomes for patients with cervical spine challenges.

Level of Evidence: 2b     

Indian consensus on the management of CRE infection in critically ill patients (ICONIC) — India

Background: The increasing burden of carbapenem-resistant Enterobacteriaceae (CRE) carriage and infection in different patient settings in India has created an acute need for guidance for clinicians regarding optimal strategies for the management of CRE infection in critically ill patients.

Research design and methods: A multidisciplinary panel of 11 Indian experts in CRE infection assembled for comprehensive discussion and consensus development. The experts developed clinical statements through a systematic review of key literature.

Main outcome measures: The panel voted anonymously on 60 clinically relevant questions, through a modified Delphi process.

Results: Forty-six key clinical consensus statements (CCS) were proposed. The panel reached a consensus on several important issues, providing recommendations on surveillance, diagnosis, prevention, pharmacokinetic challenges, combination therapy, and cornerstone molecules in CRE infections. The panel also proposed a treatment algorithm for NDM-prevalent settings.

Conclusion: These consensus statements may offer clinicians expert guidance on the management of CRE infections. There is a dearth of high-/moderate-level evidence on managing CRE infections; the recommendations presented herein are based on expert opinion.     

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.     

Reliability and validity of measurements of cervical retraction strength obtained with a hand-held dynamometer

Objectives: The purpose of this study was to describe the reliability and validity of measurements of cervical retraction strength obtained with a hand held dynamometer (HHD) from healthy adults.

Background: Impaired neck muscle strength is related to neck pain, abnormal posture, and various cervical pathologies. While sophisticated devices to objectively measure neck strength exist, many are not practicable in typical orthopedic practices or have questionable validity and reliability.

Methods: Forty participants were included in the analysis of neck strength using isometric testing with an HHD fixed in a cradle on a table top. The highest neck retraction force recorded in Newtons (N) for each participant, was used for data analysis.

Results: Both intratester and intertester reliability were excellent as judged by intraclass correlation coefficients (ICCs) (.885 – .974) and minimal detectable change (MDC) (21.1 to 47.6 N). Validity was confirmed on the basis of expected gender and age differences (ie, men were stronger than women and younger participants were stronger than older participants).

Conclusion: Fixed HHD is a reliable and valid tool for measuring isometric neck retraction strength in ostensibly healthy adults. Its value in the assessment of individuals with neck pathology awaits further examination.     

Reference-less MR thermometry on pre-clinical thiel human cadaver for liver surgery with MRgFUS

Purpose: Reference-less MR thermometry can be a promising technique for temperature mapping during liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS), as it is more robust to breathing motion than Proton Resonance Frequency MR thermometry. However, there is a lack of a pre-clinical model for repeatable testing of reference-less thermometry. The purpose of this work was to verify the explanted Thiel embalmed human liver and whole Thiel embalmed human cadaver for application of a custom made reference-less thermometry algorithm during MRgFUS sonication.

Material and methods: Phase maps were generated during sonication as an input to the algorithm. A square Region-of-Interest (ROI) was designed around the heated area. The ROI was interpolated using a two-dimensional polynomial to the surrounding phase map to calculate the background phase.

Results: Using the phase information from the images, the temperature rise was measured. Validation of the methodology showed accordance of temperatures with actual temperatures.

Conclusions: The explanted liver and the whole cadaver constitute a promising and feasible model to study reference-less techniques for thermometry during MRgFUS, before clinical trials.     

Diagnostic accuracy and validity of three manual examination tests to identify alar ligament lesions: results of a blinded case-control study

Introduction: Tests to evaluate the integrity of the alar ligaments are important clinical tools for manual therapists, but there is limited research regarding their validity.

Method: A single blinded examiner assessed alar ligament integrity using the lateral shear test (LST), rotation stress test (RST) and side-bending stress test (SBST) on a sample of convenience comprising 7 subjects with MRI confirmed alar ligament lesions and 11 healthy people. Alar ligament lesions were identified using both supine and high-field strength upright MRI.

Results: The RST had a sensitivity of 80% and a specificity of 69.2%. The SBST and the LST both showed a sensitivity of 80% and a specificity of 76.9%. In cases where all three tests were positive, the specificity increased to 84.6%.

Discussion: Tests of manual examination of alar ligament integrity have some diagnostic utility; however, these findings require further corroboration in a larger sample.     

Accuracy of genotyping for HPV16 and 18 to triage women with low-grade squamous intraepithelial lesions: a pooled analysis of VALGENT studies

Background: Genotyping for the most carcinogenic human papillomavirus (HPV) types (HPV16/HPV18) can identify high risk of underlying cervical precancer and guide further management.

Research design and methods: A pooled analysis was performed of the clinical accuracy of high-risk HPV (hrHPV) testing and HPV16/18 genotyping in triage of women with low-grade squamous intraepithelial lesions (LSIL). Data regarding 24 assays evaluated in four VALGENT validation panels were used.

Results: In women with LSIL, hrHPV had a pooled sensitivity for CIN2+ of 95.5% (95% CI: 91.0–97.8%) and a specificity of 25.3% (95% CI: 22.2–28.6%). HPV16/18 genotyping had a sensitivity and specificity for CIN2+ of 52.9% (95% CI: 48.4–57.4%) and 83.5% (95% CI: 79.9–86.5%), respectively. The average risk of CIN2+ was 46.1% when HPV16/18-positive, 15.5% in women who were HPV16/18-negative but positive for other hrHPV types and 4.3% for hrHPV-negative women.

Conclusions: Triage of women with LSIL with HPV16/18 genotyping increases the positive predictive value compared to hrHPV testing but at the expense of lower sensitivity. Arguably, women testing positive for HPV16/18 need further clinical work-up. Whether colposcopy referral or further surveillance is recommended for women with other hrHPV types may depend on the post-test risk of precancer and the local risk-based decision thresholds.     

Triage for out-of-hours primary care calls: a reliability study of a new French-language algorithm,the SALOMON rule

Introduction: Triage systems for out-of-hours primary care physician (PCP) calls have been implemented empirically but no triage algorithm has been validated to date. A triage algorithm named SALOMON (Système Algorithmique Liégeois d’Orientation pour la Médecine Omnipraticienne Nocturne) was developed to guide triage nurses. This study assessed the performance of the algorithm using simulated PCP calls.

Methods: Ten nurses were involved in 130 simulated PCP call scenarios, allowing the determination of SALOMON’s inter-rater agreement by comparing the actual choices of a specific triage flowchart and the level of care selected as compared with reference assignments. Intra-rater agreement was estimated by comparing triage after training (T1) and 3 to 6 months after SALOMON use in clinical practice (T2).

Results: Overall selection of flowcharts was accurate for 94 .1% of scenarios at T1 and 98.7% at T2. Level of triage was adequate for 93.4% of scenarios at T1 and 98.5% at T2. Both flowchart and triage level accuracy improved significantly from T1 to T2 (p?<?0.0001). SALOMON algorithm use is associated with a 0.97/0.99 sensitivity and 0.97/0.99 specificity, at T1/T2 respectively.

Conclusions: Results revealed that using the SALOMON algorithm is valid for out-of-hours PCP calls triage by nurses. The criterion validity of this algorithm should be further evaluated through its implementation in a real life setting.