Relationship of polypharmacy to HIV RNA suppression in people aged ≥ 50 years living with HIV.

OBJECTIVES: People living with HIV (PLWH) aged ≥ 50 years face unique challenges regarding their medication therapies, especially antiretroviral therapy (ART). Use of ARTs, along with medications for comorbidities, may lead to adverse events, drug-drug interactions (DDIs) and poor adherence. The objective of this study was to identify the number of medications above which PLWH aged ≥ 50 years are less likely to be virally suppressed and to describe other associated patient-specific risk factors. METHODS: This was a cross-sectional study of PLWH aged ≥ 50 years, prescribed ART, and seen at least once in the Northwestern Infectious Disease Center between 1 June 2013 and 31 May 2015. Variables concerning medication use and comorbidities were collected. The primary outcome was the presence of an undetectable plasma HIV RNA level (viral load). RESULTS: Among the 621 included patients, there was a higher percentage taking ≤ 15 medications with an undetectable plasma HIV RNA (n = 453; 80.6%) vs. patients taking > 15 medications (n = 40; 67.8%; P = 0.03). Taking > 15 medications [odds ratio (OR) 0.49; 95% confidence interval (CI) 0.26-0.96], pulmonary disease (OR 0.54; 95% CI 0.3-0.97) and CD4 T-lymphocyte count < 200 cells/µL (OR 0.39; 95% CI 0.22-0.68) decreased the odds of having an undetectable plasma HIV RNA. CONCLUSIONS: PLWH taking > 15 medications were less likely to have an undetectable HIV RNA. Further studies are needed to evaluate the impact of overall medication economic burden on clinical outcomes among PLWH ≥ 50 years of age.

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.

Quantifying regeneration in patients following peripheral nerve injury.

Healthy nerve function provides humans with the control of movement; sensation (such as pain, touch and temperature) and the quality of skin, hair and nails. Injury to this complex system creates a deficit in function, which is slow to recover, and rarely, if ever, returns to what patients consider to be normal. Despite promising results in pre-clinical animal experimentation effective translation is challenged by a current inability to quantify nerve regeneration in human subjects and relate this to measurable and responsible clinical outcomes. In animal models, muscle and nerve tissue samples can be harvested following experimental intervention. This allows direct quantification of muscle mass and quality and quantity of regeneration of axons; such an approach is not applicable in human medicine as it would ensure a significant functional deficit. Nevertheless a greater understanding of this process would allow the relationship that exists between neural and neuromuscular regeneration and functional outcome to be more clearly understood. This article presents a combined commentary of current practice from a specialist clinical unit and research team with regard to laboratory and clinical quantification of nerve regeneration. We highlight how electrophysiological diagnostic methods (which are used with significant recognised limitations in the assessment of clinical medicine) can potentially be used with more validity to interpret and assess the processes of neural regeneration in the clinical context, thus throwing light on the factors at play in translating lab advances into the clinic.

An assessment of fatigability following nerve transfer to reinnervate elbow flexor muscles.

AIMS: Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation. PATIENTS AND METHODS: This retrospective cohort study included 12 patients who underwent Oberlin nerve transfer in an attempt to restore flexion of the elbow following brachial plexus injury. There were ten men and two women with a mean age of 45.5 years (27 to 69). The mean follow-up was 58 months (28 to 100). Repeated and sustained isometric contractions of the elbow flexors were used to assess fatigability of reinnervated muscle. The strength of elbow flexion was measured using a static dynamometer (KgF) and surface electromyography (sEMG). Recordings were used to quantify and characterize fatigability of the reinnervated elbow flexor muscles compared with the uninjured contralateral side. RESULTS: The mean peak force of elbow flexion was 7.88 KgF (sd 3.80) compared with 20.65 KgF (sd 6.88) on the contralateral side (p < 0.001). Reinnervated elbow flexor muscles (biceps brachialis) showed sEMG evidence of fatigue earlier than normal controls with sustained (60-second) isometric contraction. Reinnervated elbow flexor muscles also showed a trend towards a faster twitch muscle fibre type. CONCLUSION: The assessment of motor outcomes must involve more than peak force alone. Reinnervated muscle shows a shift towards fast twitch fibres following reinnervation with an earlier onset of fatigue. Our findings suggest that fatigue is a clinically relevant characteristic of reinnervated muscle. Adoption of these metrics into clinical practice and the assessment of outcome could allow a more meaningful comparison to be made between differing forms of treatment and encourage advances in the management of motor recovery following nerve transfer. Cite this article: Bone Joint J 2019;101-B:867-871.

Survey of screening methods, rates and policies for the detection of carbapenemase-producing Enterobacteriaceae in English hospitals.

Multi-drug-resistant Gram-negative bacteria are of major clinical concern. The increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE), resistant to all beta-lactams including carbapenems and able to colonize the large intestine, represents a key threat. Rapid, accurate detection of intestinal CPE colonization is critical to minimize transmission, and hence reduce costly, difficult-to-treat CPE infections. There is currently no 'gold standard' CPE detection method. A survey of diagnostic laboratories in England found considerable heterogeneity in diagnostic CPE testing methods and procedures.

Evaluation of the novel artus C. difficile QS-RGQ, VanR QS-RGQ and MRSA/SA QS-RGQ assays for the laboratory diagnosis of Clostridium difficile infection (CDI), and for vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) screening.

Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are worldwide prevalent healthcare-associated pathogens. We have evaluated three Qiagen artus QS-RGQ assays for the detection of these pathogens. We examined 200 stool samples previously tested for C. difficile infection (CDI), 94 rectal swabs previously screened for VRE and 200 MRSA screening nasal swabs. With the routine diagnostic laboratory results being adopted as the gold standard, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the artus C. difficile assay were 100%, for the artus VanR QS-RGQ assay, 95, 68, 44 and 98%, and for the artus MRSA/SA assay, 80, 94, 93 and 83%, respectively. The artus VanR assay detected the vanA and/or vanB genes in 32% of culture-negative VRE screens; in 71% of these cases, only vanB was detected. An over-estimation of the rate of faecal VRE colonisation could be due to a patient population with high rates of faecal carriage of non-enterococcal species carrying vanB. Based on our findings, we conclude that all three artus QS-RGQ assays could be a useful addition to a diagnostic laboratory, and that the optimal choice of assay should be determined according to user needs.

Overcoming barriers to effective recognition and diagnosis of Clostridium difficile infection.

With the frequency of cases of Clostridium difficile infection (CDI) increasing in many developed countries, accurate and reliable laboratory diagnosis of CDI is more important than ever. However, the diagnosis of CDI has been handicapped by the existence of two reference standards, one of which detects C. difficile toxin (cytotoxin assay) and the other only toxigenic strains (cytotoxigenic culture). Being relatively slow and laborious to perform, these reference methods were largely abandoned as routine diagnostic methods for toxin detection in favour of stand-alone rapid enzyme immunoassays (EIAs), which have suboptimal sensitivity and specificity. The management of CDI is undermined by high rates of both false-positive and false-negative test results. More recently developed nucleic acid amplification tests (NAATs) for toxin gene detection offer improved sensitivity over immunoassays, but fail to discriminate between CDI and asymptomatic colonization with C. difficile, and have clear drawbacks as stand-alone diagnostic tests. Two-step or three-step diagnostic algorithms have been proposed as a solution. In a large study of the effectiveness of currently available tests, a diagnostic algorithm was developed that combines available tests to more effectively distinguish patients with CDI from uninfected patients. This two-test protocol, which is now used in National Health Service laboratories in England, comprises an EIA for glutamate dehydrogenase detection or NAATs for toxin gene detection, followed by a relatively sensitive toxin EIA. This algorithm also identifies 'potential C. difficile excretors', individuals with diarrhoeal samples that contain C. difficile but without demonstrable toxin, who may be a source of transmission of C. difficile to susceptible patients.

MRSA prevention strategies and current guidelines.

We review prevention strategies to minimise the risk of MRSA soft tissue and bone infections, which can be devastating for the patient and costly for the healthcare provider. Department of Health (England) policy is that screening for emergency admissions will be mandatory from 2011, in addition to existent elective admission screening. Rapid screening technology has not been shown to be cost-effective, meaning that there will be a lag time between admission and the patient's MRSA status being known. Thus, standard infection control policies regarding isolation of high-risk patients will remain, with a continuing focus on MRSA decolonisation, aimed at minimising the risks of auto-infection and transmission to other patients. Antimicrobial prescribing policies should be designed to take into account the local burden of resistant organisms, but also minimise unnecessary antibiotic use. There is an increasing realisation that reducing the use of fluoroquinolones and third-generation cephalosporins (which have been associated with increased carriage of MRSA) in patient populations where MRSA is prevalent can be a useful control measure. Prevention of orthopaedic infections clearly involves general operating theatre protocols, such as suitable antiseptic skin preparation, and additional measures including the use of laminar airflow. Antibiotic prophylaxis is adjusted in patients known to have MRSA to include a glycopeptide, and local guidelines may adopt such regimens for all patients due to the burden of MRSA in the local patient population. A future development that may have an effect on practice is the development of a Staphylococcus aureus vaccine, which has been shown to be cost-effective in a computer-modelled evaluation.

Participation as a basis for developing early intervention outcomes.

PURPOSE: This article describes how participation in activities/routines can be used as a basis for understanding children's communication and language skills and how that knowledge can be extended to collaborate with families and caregivers to develop meaningful early intervention outcomes. METHOD: The approach is centered on children's use of communication and language skills to participate in typical activities/routines. Implementation of the approach is based on an understanding of children's performance abilities/disabilities and their use of those abilities to participate in family-identified activities/routines in their natural environments. Discussion and case examples illustrate how communication and language skills can enhance or enable participation in such activities. Family-centered procedures for gathering information about activities/routines from caregivers are described, and strategies for developing outcomes in collaboration with caregivers are presented. IMPLICATIONS: Participation-based outcomes offer speech-language pathologists an option for embedding skills within important activities/routines, thereby promoting children's communication and language growth in natural contexts.