Serological studies in the elderly.

Sera from 108 elderly patients in psychiatric and general hospitals were tested for antibodies to seven viruses. Measles virus antibody levels were significantly higher in patients from the psychiatric hospital, regardless of diagnosis, than in those from other hospitals. Demented patients, regardless of their hospital, had significantly higher levels of antibody to adenovirus than control patients.     

Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation

To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring. Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings. The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient. These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient.     

Understanding HIV-Related Pill Aversion as a Distinct Barrier to Medication Adherence

Abstract

Pill aversion, defined as difficulty swallowing pills without identifiable medical cause, is a poorly characterized barrier to sustained viral suppression for many HIV-infected persons. We aimed to quantify the frequency of self-reported pill aversion, characterize its symptoms, and measure the association between self-reported pill aversion and missing antiretroviral doses. This is a prospective, observational, exploratory survey study of English-speaking persons living with HIV (PLHIV) at a single urban tertiary outpatient clinic. Participants completed anonymous questionnaires about their experiences of swallowing antiretroviral pills. The primary outcome was skipping pills due to pill aversion symptoms. Of 384 participants, a quarter (25.5%) skipped pills due to pill aversion symptoms. Younger age, being Non-Hispanic Black or Hispanic, not being married or partnered, having public insurance, not being employed, having less than a college education, and having a mental health diagnosis were associated with skipping pills due to pill aversion. On multivariable regression analyses, PLHIV who skipped pills were more likely to report symptoms of gagging, nausea at the time of swallowing, and heavy feeling in the stomach, as well as being bothered by the taste, smell, and size of the pills. PLHIV who skipped pills were also more likely to report negative and fear-based emotions about pill-taking than PLHIV who did not skip pills due to pill aversion. HIV-related pill aversion may represent a significant and frequent barrier to adherence in an adult HIV population.     

Accurately Identifying Low‐Allelic Fraction Variants in Single Samples with Next‐Generation Sequencing: Applications in Tumor Subclone Resolution

Current methods for resolving genetically distinct subclones in tumor samples require somatic mutations to be clustered by allelic frequencies, which are determined by applying a variant calling program to next‐generation sequencing data. Such programs were developed to accurately distinguish true polymorphisms and somatic mutations from the artifactual nonreference alleles introduced during library preparation and sequencing. However, numerous variant callers exist with no clear indication of the best performer for subclonal analysis, in which the accuracy of the assigned variant frequency is as important as correctly indicating whether the variant is present or not. Furthermore, sequencing depth (the number of times that a genomic position is sequenced) affects the ability to detect low‐allelic fraction variants and accurately assign their allele frequencies. We created two synthetic sequencing datasets, and sequenced real KRAS amplicons, with variants spiked in at specific ratios, to assess which caller performs best in terms of both variant detection and assignment of allelic frequencies. We also assessed the sequencing depths required to detect low‐allelic fraction variants. We found that VarScan2 performed best overall with sequencing depths of 100×, 250×, 500×, and 1,000× required to accurately identify variants present at 10%, 5%, 2.5%, and 1%, respectively.     

Mutation Detection by Clonal Sequencing of PCR Amplicons and Grouped Read Typing is Applicable to Clinical Diagnostics

We describe a sensitive technique for mutation detection using clonal sequencing. We analyzed DNA extracted from 13 cancer cell lines and 35 tumor samples and applied a novel approach to identify disease‐associated somatic mutations. By matching reads against an index of known variants, noise can be dramatically reduced, enabling the detection and quantification of those variants, even when they are present at less than 1% of the total sequenced population; this is comparable to, or better than, current diagnostic methods. Following the identification or exclusion of known variants, unmatched reads are grouped for BLAST searching to identify novel variants or contaminants. Known variants, novel variants, and contaminants were readily identified in tumor tissue using this approach. Our approach also enables an estimation of the per‐base sequencing error rate, providing a confidence threshold for interpretation of the results in the clinic. This novel approach has immediate applicability to clinical testing for disease‐associated genetic variants.     

Delivering Smoking Cessation Support by Mobile Phone Text Message: What Information do Smokers Want? A Focus Group Study

Recent advances in technology have given rise to novel methods of delivering support to smokers wanting to quit. Mobile phone text messaging permits the delivery of quitting advice at any time, with little effort and at minimal cost. We examined smokers' attitudes toward text messaging as a tool to facilitate smoking cessation as well as preferences for message content and text delivery. Six focus groups were conducted from a total of 24 participants, with additional information obtained via paper questionnaire. Interaction with the text messaging system, tailoring message content and delivery, highlighting the positive effects of quitting, and offering encouragement by text were considered important features of a text support program. Future text messaging interventions may benefit from these findings.     

Characterization of Pre-Antibiotic Era Klebsiella pneumoniae Isolates with Respect to Antibiotic/Disinfectant Susceptibility and Virulence in Galleria mellonella

The EGD Murray collection consists of approximately 500 clinical bacterial isolates, mainly Enterobacteriaceae, isolated from around the world between 1917 and 1949. A number of these “Murray” isolates have subsequently been identified as Klebsiella pneumoniae. Antimicrobial susceptibility testing of these isolates showed that over 30% were resistant to penicillins due to the presence of diverse bla_SHV β-lactamase genes. Analysis of susceptibility to skin antiseptics and triclosan showed that while the Murray isolates displayed a range of MIC/minimal bactericidal concentration (MBC) values, the mean MIC value was lower than that for more modern K. pneumoniae isolates tested. All Murray isolates contained the cation efflux gene cepA, which is involved in disinfectant resistance, but those that were more susceptible to chlorhexidine were found to have a 9- or 18-bp insertion in this gene. Susceptibility to other disinfectants, e.g., H₂O₂, in the Murray isolates was comparable to that in modern K. pneumoniae isolates. The Murray isolates were also less virulent in Galleria and had a different complement of putative virulence factors than the modern isolates, with the exception of an isolate related to the modern lineage CC23. More of the modern isolates (41% compared to 8%) are classified as good/very good biofilm formers, but there was overlap in the two populations. This study demonstrated that a significant proportion of the Murray Klebsiella isolates were resistant to penicillins before their routine use. This collection of pre-antibiotic era isolates may provide significant insights into adaptation in K. pneumoniae in relation to biocide susceptibility.