The interpretation of hair analysis for drugs and drug metabolites

Introduction: Head hair analysis for drugs and drug metabolites has been used widely with the aim of detecting exposure in the weeks or months prior to sample collection. However, inappropriate interpretation of results has likely led to serious miscarriages of justice, especially in child custody cases.

Objective: The aim of this review is to assess critically what can, and perhaps more importantly, what cannot be claimed as regards the interpretation of hair test results in a given set of circumstances in order to inform future testing.

Methods: We searched the PubMed database for papers published 2010–2016 using the terms “hair” and “drug” and “decontamination”, the terms “hair” and “drug” and “contamination”, the terms “hair” and “drug-facilitated crime”, the terms “hair” and “ethyl glucuronide”, and the terms “hair”, “drug testing” and “analysis”. Study of the reference lists of the 46 relevant papers identified 25 further relevant citations, giving a total of 71 citations.

Hair samples: Drugs, drug metabolites and/or decomposition products may arise not only from deliberate drug administration, but also via deposition from a contaminated atmosphere if drug(s) have been smoked or otherwise vaporized in a confined area, transfer from contaminated surfaces via food/fingers, etc., and transfer from sweat and other secretions after a single large exposure, which could include anesthesia. Excretion in sweat of endogenous analytes such as γ-hydroxybutyric acid is a potential confounder if its use is to be investigated. Cosmetic procedures such as bleaching or heat treatment of hair may remove analytes prior to sample collection. Hair color and texture, the area of the head the sample is taken from, the growth rate of individual hairs, and how the sample has been stored, may also affect the interpretation of results.

Toxicological analysis: Immunoassay results alone do not provide reliable evidence on which to base judicial decisions. Gas or liquid chromatography with mass spectrometric detection (GC- or LC-MS), if used with due caution, can give accurate analyte identification and high sensitivity, but many problems remain. Firstly, it is not possible to prepare assay calibrators or quality control material except by soaking “blank” hair in solutions of appropriate analytes, drying, and then subjecting the dried material to an analysis. The fact that solvents can be used to add analytes to hair points to the fact that analytes can arrive not only on, but also in hair from exogenous sources. A range of solvent-washing procedures have been advocated to “decontaminate” hair by removing adsorbed analytes, but these carry the risk of transporting adsorbed analytes into the medulla of the hair therefore confounding the whole procedure. This is especially true if segmental analysis is being undertaken in order to provide a “time course” of drug exposure.

Proposed clinical applications of hair analysis: There have been a number of reports where drugs seemingly administered during the perpetration of a crime have been detected in head hair. However, detailed evaluation of these reports is difficult without full understanding of the possible effects of any “decontamination” procedures used and of other variables such as hair color or cosmetic hair treatment. Similarly, in child custody cases and where the aim is to demonstrate abstinence from drug or alcohol use, the issues of possible exogenous sources of analyte, and of the large variations in analyte concentrations reported in known users, continue to confound the interpretation of results in individual cases.

Conclusions: Interpretation of results of head hair analysis must take into account all the available circumstantial and other evidence especially as regards the methodology employed and the possibility of surface contamination of the hair prior to collection.     

Trends in carisoprodol abuse and misuse after regulatory scheduling: a retrospective review of California poison control calls from 2008 to 2015

Background: In January 2012, carisoprodol was classified as a Schedule IV substance under the controlled substances act from a previously non-controlled, non-scheduled classification. Carisoprodol is marketed as a skeletal muscle relaxant and is commonly cited for its abuse potential.

Objectives: We aimed to compare volume of calls involving carisoprodol abuse or misuse to a statewide poison control system before and after the scheduling change.

Methods: Data were extracted from poison control calls coded as “misuse/abuse” involving carisoprodol from four years before (2008 to 2011) and four years after (2012 to 2015) the scheduling change. The volume of calls from pre- and post-scheduling change was compared after adjusting for yearly California census data.

Results: The number of calls related to carisoprodol abuse or misuse was significantly decreased in the four years following the change compared to the four years before.

Conclusion: Scheduling of carisoprodol was temporally related to decreased exposures as reported to California Poison Control Centers. Governmental regulation may impact a drug’s potential for abuse.     

Drug-associated pulmonary arterial hypertension

Introduction: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into “definite”, “likely”, “possible”, or “unlikely” to cause pulmonary arterial hypertension, based on the strength of evidence.

Objective: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.

Methods: A systematic search was conducted using PubMed covering the period September 1970– 2017. The search term utilized was “drug induced pulmonary hypertension”. This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism.

Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension.

Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection.

Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear.

Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension.

Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports.

Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension.

Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes.

Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.

Conclusions: Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.     

Primary-care-based episodes of care and their costs in a three-month follow-up in Finland

Objective To explore patient characteristics, resource use, and costs related to different episodes of care (EOC) in Finnish health care.

Design Data were collected during a three-month prospective, non-randomized follow-up study (Effective Health Centre) using questionnaires and an electronic health record.

Setting Three primary health care practices in Pirkanmaa, Finland.

Subjects Altogether 622 patients were recruited during a one-week period. Inclusion criteria: the patient had a doctor’s or nurse’s appointment on the recruiting day and agreed to participate. Exclusion criteria: patients visiting a specialized health guidance clinic for pregnant women, children, and mothers.

Main outcome measures Patient characteristics, resource use, and costs based on the ICPC-2 EOC classification.

Results On average, the patients had 1.22 EOCs during the three months. Patient characteristics and resource use differed between the EOC chapters. Chapter L, “Musculoskeletal”, had the most episodes (17%). The most common (8%) single EOC was “upper respiratory infection”. The mean cost of an episode (COE) was €389.56 (standard error 61.11) and the median COE was €165.00 (interquartile range €118.46–288.56) during the three-month follow-up. The most expensive chapter was K, “Circulatory”, with a mean COE of €909.85. The most expensive single COE was in chapter K, €32 545.56. The most expensive 1% of the COEs summed up covered 36% of the total COEs.

Conclusion Patient characteristics, resource use, and costs differed between the ICPC-2 chapters, which could be taken into account in service planning and pricing. Future studies should incorporate more specific diagnoses, larger data sets, and longer follow-up times.

• Key points

• The most common episodes were under the ICPC-2 “Musculoskeletal” chapter, but the highest mean and single-episode costs were related to the “Circulatory” chapter.

• The mean (median) cost of episodes that started in primary care was €390 (€165) during the three-month follow-up.

• Patient characteristics, resource use, and costs differed significantly between the ICPC-2 chapters. The most expensive 1% of the episodes covered 36% of the total costs of all the episodes.

     

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.     

Being “just normal”: a grounded theory of prosthesis use

Purpose: Whilst research tells us about the benefits and challenges of using prostheses, little attempt has been made to account for and provide explanations for the differing experiences of prosthesis users. In this study, a core concern shared by prosthesis users and an account of how this concern is managed are explored.

Method: Data were collected and analysed according to Grounded Theory procedures, involving interviews with 24 participants, 17 weblogs, 17 autobiographical texts, and posts from 4 online forums.

Results: Prosthesis users are primarily concerned with being “just normal”: the condition of being and living in ways that persons variously perceive are “about right”; that are sufficient, fair, and generally how things “ought to be” for them. This concern is acted upon through: (i) “preserving”, where persons foresee and manage threats to being “just normal”, (ii) “redressing”, involving rectifying things judged not to be “just normal”, and (iii) “persevering”, where persons keep living “just normally” despite accompanying difficulties.

Conclusions: “Just normal” is a new means for rehabilitation practitioners to better understand a key concern of prosthesis users and the motivations underlying behaviours in their prosthesis use. It is also relevant and transferable to broader fields of assistive technology use and disability.

• Implications for Rehabilitation

• The grounded theory of “just normal” invites practitioners to discover a key concern in prosthesis use, enabling a richer understanding of the needs and desires of service users.

• Being “just normal” is presented as an important motivator underlying a range of diverse actions within prosthesis use.

• The theory is relevant and transferable to broader areas of assistive technology use and disability.

     

Central nervous system malformation associated with methamphetamine abuse during pregnancy

Introduction: Prenatal methamphetamine exposure is related to prematurity, fetal growth restriction, neurobehavioral effects and long-term motor and cognitive sequelae.

Patient presentation: We report the case of a newborn from a Filipina with no prenatal care with a complex brain malformation. Methamphetamine was identified in maternal and neonatal urine and in maternal hair, raising our suspicion of methamphetamine as a cause of this malformation.

Discussion: Methamphetamine abuse is a growing problem worldwide. There are little data on its effect on the fetus. To our knowledge, no fetal brain abnormalities have been associated with its use. In our case, the lack of antenatal control does not allow us to date when this malformation appeared.

Conclusion: The aim of our report is to generate awareness of the possible association between methamphetamine abuse during pregnancy and central nervous system malformations.     

Critical limb ischemia update and the evolving role of drug-elution technologies

Introduction: Critical limb ischemia (CLI) is a prevalent condition associated with cardiovascular mortality and limb loss.

Areas covered: This review discusses the epidemiology of CLI, revascularization options, and drug-elution therapies.

Expert commentary: Drug-eluting stents (DES) and drug-coated balloons (DCB) improve patency rates in the femoropopliteal segment, and are generally used as first-line therapies. For below-knee disease, angioplasty is the default strategy unless lesions are focal whereby DES can be used to reduce restenosis risk.     

Synthetic cannabinoid “Black Mamba” infidelity in patients presenting for emergency stabilization in Colorado: a P SCAN Cohort

Background: Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. “Black Mamba”, often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death.

Objectives: We aim to identify the chemical constituents and quantification of eight cases of reported “Black Mamba” use in order to further understand the clinical variability in patients presenting for emergency stabilization.

Methods: We report data from eight cases of reported “Black Mamba” use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds.

Results: In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations.

Conclusions: The wide range of clinical presentations from “Black Mamba” use may be explained by the wide variability of chemical constituents found by laboratory analysis.     

A European survey of perendoscopic treatment of biliary complications in patients with alveolar echinococcosis

Background: Biliary complications represent a turning point in the course of Alveolar Echinococcosis (AE). We conducted a European survey to collect data on the current usage and results of perendoscopic interventions (PEIs) for their treatment.

Methods: Patient’s characteristics and follow-up until January 31st, 2015 were recorded using an online questionnaire.

Results: From 18 centers 129 PEIs were analyzed in 38 patients; 139 plastic stents were inserted during 85 PEIs; median time between stent placements was significantly longer when 3 stents or more were placed. Initial symptoms disappeared in 95% and long-term bile duct patency was obtained in 73% of cases. Cholangitis was a more frequent complication of the PEIs (10%) than in other indications; intensive lavage of the bile ducts may prevent this complication.

Conclusion: European centers use perendoscopic biliary drainage as an efficient and safe alternative to surgery to treat AE biliary complications. Insertion of multiple plastic stents delays stent occlusion and leads to effective and prolonged bile duct patency.     

Pain pattern classification and directional preference for patients with neck pain

Objectives:

Pain Pattern Classification (PPC) and Directional Preference (DP) have been shown to be predictive of health care outcomes and serve to guide orthopedic clinical decision making. We conducted a prospective, observational cohort study to verify the association between PPC, DP, and clinical outcomes.

Methods:

Clinical outcome measures including pain intensity and disability were completed at first examination and follow-up by 335 patients. A Pearson’s chi-squared test was used to determine differences in prevalence rates for the categorical variables, and two-sample t-tests were used to determine differences in rates for the continuous variables. A Tukey’s range test was used to determine differences in follow-up pain intensity and disability for neck pain dual-classification schemes.

Results:

The prevalence of DP was 82.4%. The prevalence of CEN, Non-CEN, and Non-Classifiable (NC) was 15.2%, 42.1%, and 25.1%, respectively. The prevalence of DP was lowest for patients with sub-acute symptoms and who were <45 years old. Patients classified as DP CEN had, on average 2.62 NDI units less than patients classified as Non-DP. Patients classified as DP CEN had, on average, 0.90 pain intensity units less than patients classified as Non-DP at follow-up. Patients who demonstrated DP CEN did not have clinically significant lower pain intensity or disability at follow-up than patients who demonstrated Non-DP.

Discussion:

The results of this investigation need to be interpreted with caution with respect to the study design and it’s subsequent strengths and limitations.

Level of Evidence:

1b.     

Repetition of intentional drug overdose: a population-based study

Context: Intentional overdose is a leading method of self-harm and suicide, and repeat attempts strongly predict eventual death by suicide.

Objectives: To determine the risk of recurrence after a first intentional overdose. Secondary objectives included characterization of the temporal course and potential predictors of repeat overdose, a strong risk factor for death from suicide.

Methods: Design: Population-based cohort study.

Setting: Ontario, Canada, from 1 April 2002 to 31 March 2013.

Participants: All Ontario residents presenting to an emergency department after a first intentional overdose.

Main outcome measures: The incidence and timing of recurrent overdose.

Results: We followed 81,675 patients discharged from hospital after a first intentional overdose. Overall, 13,903 (17.0%) returned with a repeat overdose after a median interval of 288 (inter-quartile range: 62 to 834) days. Of these, 4493 (5.5%) had multiple repeat episodes. Factors associated with repeat self-poisoning included psychiatric care in the preceding year (adjusted hazard ratio [aHR] 1.55; 95% confidence interval [CI] 1.50 to 1.61), alcohol dependence (aHR 1.41; 95% CI 1.35 to 1.46) and documented depression (aHR 1.39; 95% CI 1.34 to 1.44). Female sex, rural residence, lower socioeconomic status, ingestion of psychoactive drugs and younger age were also weakly associated with repeat overdose.

Discussion: Hospital presentation for repetition of intentional overdose is common, with recurrent episodes often far removed from the first. While several factors predict overdose repetition, none is particularly strong.

Conclusion: Secondary prevention initiatives should be implemented for all individuals who present to the emergency department and survive intentional overdose.     

Yoga – a laborious way to well-being: patients’ experiences of yoga as a treatment for hypertension in primary care

Objective: The aim of the study was to describe patients’ experience of yoga as a treatment for hypertension, as well as their experience of living with hypertension.

Design: Qualitative interview study

Method and materials: In 2013–2014, in southern Sweden, patients with hypertension from three health care centres were invited to participate in a randomised controlled trial on yoga for hypertension. After completion of the study, eight women and five men (aged 35–79), who had practiced the yoga intervention, were interviewed about their experiences. We used a semi-structured interview guide according to Kvale. Qualitative analysis was conducted by systematic text condensation inspired by Malterud.

Results: Two main themes emerged during the analysis process: Yoga – a laborious way to well-being and hypertension – a silent disease. The positive experiences of doing yoga were described in terms of tranquillity and increased agility. The drawbacks were mainly linked to the time required to perform the exercises.

Living with high blood pressure and having to take medication can imply a stigma and cause concerns for future cardiovascular events. Most patients that we interviewed expressed a wish to find alternative ways to treat their high blood pressure. Participating in the yoga study was seen as a good possibility to try such an alternative way.

Conclusions: Many patients with hypertension in Swedish primary care seem to be interested in trying alternative treatments to control blood pressure. The patients in our study experienced several benefits from doing yoga, but they also pointed out difficulties in implementing yoga as a regular and permanent lifestyle change.     

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.     

Opioid drug poisonings in Ohio adolescents and young adults, 2002–2014

Context: Opioids represent a drug class that adolescents and young adults intentionally misuse and abuse. When taken on their own or with other substances in this manner, opioids pose an increased risk of overdose and potential death.

Objective: To determine trends of opioid drug poisonings among adolescents and young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data.

Methods: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug poisonings amongst 10–29 year olds. Trends were evaluated with Poisson regression. Ohio counties with higher opioid drug poisoning rates were identified using age-adjusted resident population estimates. Chi-square tests were conducted to compare these county rates to the Ohio rate.

Results: Both unintentional and intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were significant declines through 2014. Almost 40% of intentional opioid drug poisonings were for young adults aged 18–24 years. Suspected suicide poisonings were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were 60.1% male. Commonly reported substances included tramadol, heroin, and acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and ethanol were the most common substances reported in conjunction with opioids. The top four Ohio counties with significantly higher opioid drug poisoning rates than the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield.

Conclusion: This study enhances the understanding of Ohio’s opioid epidemic so that future prevention efforts and legislation can better target needed resources. Both males and females would benefit from opioid education early in their lives.     

Analysis of intentional drug poisonings using Ohio Poison Control Center Data, 2002–2014

Context: Pharmaceutical drug poisonings, especially those that are intentional, are a serious problem for adolescents and young adults. Poison control center data is a viable tool to track intentional drug poisonings in near real-time.

Objective: To determine intentional drug poisoning rates among adolescents and young adults in Ohio using poison control center data.

Methods: We analyzed data from 2002 to 2014 obtained by Ohio’s three poison control centers. Inclusion variables were calls made to the centers that had appropriate subject age (10–29 years old), subject sex, involved substance (all drug classes), and medical outcome (no effect, minor effect, moderate effect, major effect, and death). Intentional drug poisoning reports were also separated into subgroups to compare suspected suicide reports to misuse and abuse reports. Finally, resident population estimates were used to generate 2014 intentional drug poisoning rates for each county in Ohio.

Results: The most common age group for intentional drug poisonings was 18–24. Females reported more suspected suicide drug poisonings while males reported more misuse/abuse drug poisonings. The most reported drug class across all ages was analgesics. Of the 88 counties in Ohio, Hamilton, Williams, Washington, and Guernsey counties had the highest rates of intentional drug poisonings.

Conclusions: The high report rate of suspected suicides and analgesic class drugs demonstrates the need for preventative measures for adolescents and young adults in Ohio. Any interventions, along with legislative changes, will need to take place in our local communities.     

The clinical potential of low-level C-peptide secretion

Introduction: In all forms of diabetes, especially so in Type 1 diabetes (T1D), beta cell function is crucial for the course. The interest for residual beta cell function has been meagre, but increased in recent years with interventions to preserve function.

Areas covered: Importance and clinical use of C-peptide in Type 1 diabetes. Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms: “type 1 diabetes”, “C-peptide”, “beta cell function”, “HbA1c”, quality of life”, “complications”. Abstracts and reports from meetings were not included.

Expert commentary: C-peptide may help to get a correct diagnosis, and it is of practical clinical value to know degree of residual insulin secretion to diminish the risk of severe hypoglycaemia and ketoacidosis. Evidence shows that even a quite reduced beta cell function may play an important role for quality of life, for metabolic balance/control, possibility to avoid complications and even for long-term survival. Furthermore, the evidence is increasing for C-peptide being a hormone per se.     

Quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections in general practice: a RAND Appropriateness Method

Objective: To develop quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections, tailored to the Danish general practice setting.

Design: A RAND/UCLA Appropriateness Method was used.

Setting: General practice.

Subjects: A panel of nine experts, mainly general practitioners, was asked to rate the relevance of 64 quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections based on guidelines. Subsequently, a face-to-face meeting was held to resolve misinterpretations and to achieve consensus.

Main outcome measures: The experts were asked to rate the indicators on a nine-point Likert scale. Consensus of appropriateness for a quality indicator was reached if the overall panel median rating was 7–9 with agreement.

Results: A total of 50 of the 64 proposed quality indicators attained consensus. Consensus was achieved for 12 indicators focusing on the diagnostic process and 19 indicators focusing on the decision about antibiotic treatment and choice of antibiotics, respectively.

Conclusion: These newly developed quality indicators may be used to strengthen Danish general practitioners’ focus on their management of patients with acute respiratory tract infections and to identify where there is a need for future quality improvements.