The reliability of clinical judgments and criteria associated with mechanisms-based classifications of pain in patients with low back pain disorders: a preliminary reliability study

Mechanisms-based classifications of pain have been advocated for their potential to aid understanding of clinical presentations of pain and improve clinical outcomes. However, the reliability of mechanisms-based classifications of pain and the clinical criteria upon which such classifications are based are not known. The purpose of this investigation was to assess the inter- and intra-examiner reliability of clinical judgments associated with: (i) mechanisms-based classifications of pain; and (ii) the identification and interpretation of individual symptoms and signs from a Delphi-derived expert consensus list of clinical criteria associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The inter- and intra-examiner reliability of an examination protocol performed by two physiotherapists on two separate cohorts of 40 patients was assessed. Data were analysed using kappa and percentage of agreement values. Inter- and intra-examiner agreement associated with clinicians’ mechanisms-based classifications of low back (±leg) pain was ‘substantial’ (kappa  = 0.77; 95% confidence interval (CI): 0.57–0.96; % agreement  = 87.5) and ‘almost perfect’ (kappa  = 0.96; 95% CI: 0.92–1.00; % agreement = 92.5), respectively. Sixty-eight and 95% of items on the clinical criteria checklist demonstrated clinically acceptable (kappa ⩾ 0.61 or % agreement ⩾ 80%) inter- and intra-examiner reliability, respectively. The results of this study provide preliminary evidence supporting the reliability of clinical judgments associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The reliability of mechanisms-based classifications of pain should be investigated using larger samples of patients and multiple independent examiners.     

Molecular characterization of resistance to rifampicin in clinical isolates of Neisseria meningitidis

Among 3904 meningococcal isolates collected between October 2002 and June 2007 by the French Meningococcal Reference Centre, eight (0.20%) were resistant to rifampicin (Rif-R; MIC >1 mg/L) and 27 (0.69%) were intermediate-resistant to rifampicin (Rif-I; MICs between 0.38 mg/L and 1 mg/L) according to the E-test method. The MICs determined by agar dilution were lower, eliminating the E-test intermediate category. All Rif-R isolates had mutations in the rpoB gene, resulting in substitutions at or near amino acid position 552, which were absent in non-resistant isolates. These data suggest that a rifampicin clinical breakpoint of 1.0 mg/L should be adopted for Neisseria meningitidis .     

Drug repurposing and emerging adjunctive treatments for schizophrenia

Introduction: Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial. Nevertheless, the understanding of the pathophysiology of this syndrome, concise diagnostic methods and more effective and tolerable treatments are still lacking. Thus, innovative approaches and the exploration of new territories are required.

Areas covered: An overview of repurposed drugs and emerging treatments for schizophrenia is presented, focusing on randomized, controlled trials and meta-analyses.

Expert opinion: Despite many years of drug research, several needs in the treatment of schizophrenia including the safety and tolerability, stage-dependent and personalized approaches, as well as drug delivery and sustainability have not been addressed sufficiently. Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid, celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin), glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoidmodulator, represent promising agents in this field.     

Sudden gains among women receiving treatment for alcohol use disorders

Understanding the timing and types of change during treatment for mental health disorders is an important step toward elucidating possible mechanisms of behaviour change in response to therapeutic interventions, yet these issues have not been adequately addressed in the alcohol dependence treatment literature. The current study applied sudden gains (SGs) methodology, an approach originally developed in depression treatment studies, to a sample of women receiving treatment for alcohol use disorders. SGs are drastic improvements in symptoms that occur between two psychotherapy sessions and are hypothesised to be the result of what occurred in the first of those two sessions. SGs can happen at any time during the course of treatment, can happen more than once, and are individualised, as opposed to aggregated for a sample. For the current study, SGs were examined across three variables: percent drinking days (PDD), urge frequency (UF), and urge intensity (UI) in a sample of 102 women receiving either individual or couple cognitive-behavioural therapy for alcohol use disorders. Results indicated the presence of SGs; one-third of the sample experienced at least one SG in either alcohol use or urges to drink; the most common SGs were in frequency of urges to drink. SGs in urge frequency during treatment predicted better post-treatment drinking outcome.     

Phase Diagram of Sodium Hexametaphosphate and Poly(allylamine hydrochloride) Mixtures and In Situ Monitoring of Step‐by‐Step Deposition in This Polyelectrolyte System

The step‐by‐step deposition of poly(allylamine hydrochloride) (PAH) and sodium hexameta­phosphate (PSP) leads to coatings displaying interesting intumescent properties and is a fascinating model system to understand the fundamental mechanism behind such a deposition process. In this investigation, the deposition kinetics of (PAH‐PSP)_n is followed in situ by means of a quartz crystal microbalance with dissipation monitoring, as a function of NaCl concentration. The evolution of the film deposition is analyzed in detail and the data are compared with previous data obtained by ellipsometry on dried films. These results are also compared with the expectations from the PAH/PSP phase diagram. The (PAH‐PSP)_n films are also able to incorporate hexacyanoferrate anions with an amount of an incorporated redox probe reflecting the film thickness as obtained in the presence of eletrolyte solutions of increasing ionic strength. The in situ measurements and the electrochemical probe experiments reveal details of the film deposition mechanism that are not accessible by dry‐state characterization methods.

     

Mechanisms of antimicrobial resistance among hospital-associated pathogens

Introduction: The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice.

Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi.

Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.     

Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward ‘molecularly targeted’ therapy

Introduction: Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of ‘serious’ by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients.

Areas covered: In this review, we summarize the clinical impact, presentations, and mechanisms of resistance of these four major groups of non-fermenting Gram-negative bacilli. We also describe available and promising novel therapeutic options and strategies, particularly combination antibiotic strategies, with a focus on multidrug resistant variants.

Expert commentary: We finally advocate for a therapeutic approach that incorporates in vitro antibiotic susceptibility testing with molecular and genotypic characterization of mechanisms of resistance, as well as pharmacokinetics and pharmacodynamics (PK/PD) parameters. The goal is to begin to formulate a precision medicine approach to antimicrobial therapy: a clinical-decision making model that integrates bacterial phenotype, genotype and patient’s PK/PD to arrive at rationally-optimized combination antibiotic chemotherapy regimens tailored to individual clinical scenarios.     

Understanding Interactions Between Chinese Medicines and Pharmaceutical Drugs in Integrative Healthcare

In the 21 st century,the public are more informed,mainly via the Internet,about health and medical products and have become more knowledgeable about matters relating to their health conditions and well-being in curing and preventing illnesses.They often self-medicate themselves with various health products and over-the-counter(OTC) medicines apart from prescribed pharmaceutical drugs(PD).Some of those non-prescribed products may have doubtful quality control and contain harmful additives or unchecked ingredients;thus their usefulness is in doubt.The increasing popularity world-wide of using Chinese medicines(CM) and related OTC functional products has raised concerns over their concomitant use with PD and the consequential adverse effects.In most cases the alleged causes of adverse effects are linked with herbal sources,although the authorised information on the interactions between CM-PD is not plentiful in the literature.There is an urgent need for such a data base.The future professionals in health and medical care should be knowledgeable or aware of what their patients have been taking or given.In actual practice the patients may receive both treatments intentionally or unintentionally,with or without the awareness of the practitioner.In these situations a reliable database for interactions between CM-PD will be extremely useful for consultation when treatment problems appear or during emergency situations.Their combining of medications may be involved with possible outcomes of adverse reactions or beneficial effects.Such a database will be welcomed by both practitioners of herbal medicines and orthodox medicine practitioners in the emerging trend of integrative medicine.The author has been involved in various research projects of basic and clinical aspects in mainly CM among other herbal and PD.Examples will be given largely on those related to these disciplines as illustrations in this overview.