Plus Sutures for preventing surgical site infection: a systematic review of clinical outcomes with economic and environmental models.

BACKGROUND: Surgical site infections (SSIs) represent ~ 20% of all hospital-acquired infections in surgical patients and are associated with prolonged hospital stay, admission to intensive care, and mortality. We conducted a systematic review with economic and environmental models to assess whether triclosan-coated sutures (Plus Sutures) provide benefits over non-coated sutures in the reduction of SSI risk. METHODS: Searches were conducted in fifteen databases. A total of 1,991 records were retrieved. Following deduplication and screening by two independent reviewers, 31 randomized controlled trials in adults and children were included in the review. Similarity of the studies was assessed by narrative review and confirmed by quantitative assessment. A fixed effects meta-analysis of SSI incidence model including all groups of patients estimated a risk ratio of 0.71 (95% confidence interval: 0.64 to 0.79) indicating those in the Plus Sutures group had a 29% reduction in the risk of developing an SSI compared with those in the control group (p < 0.001). Safety outcomes were analysed qualitatively. RESULTS: The economic model estimated the use of Plus Sutures to result in average cost savings of £13.63 per patient. Plus Sutures remained cost-saving in all subgroup analyses with cost-savings ranging between £11 (clean wounds) and £140 (non-clean wounds). The environmental impact of SSI is substantial, and the model suggests that the introduction of Plus Sutures could result in potential environmental benefits. CONCLUSIONS: The evidence suggests that Plus Sutures are associated with a reduced incidence of SSI across all surgery types alongside cost savings when compared with standard sutures.

Lessons Learned or Forgotten? Impacts of COVID-19 on the Future Direction of Global (e-)Mental Health Care.

PURPOSE OF REVIEW: The COVID-19 pandemic has impacted lives globally, posing unique challenges to mental health services exposing vulnerability and limitations within these systems. During the course of the pandemic, telecommunications technologies (e-mental health care) have served a critical role in psychiatric care. It is important to understand current lessons learned in e-mental health care and implications for global mental health systems for both emerging from the pandemic and after the pandemic has ended. RECENT FINDINGS: There are significant regulatory, policy, and evaluation challenges for global e-mental health impacting patients, clinicians, health systems, and decision-makers. These include complex regulatory issues, difficulties of providing care across boundaries, and keeping pace with the implementation of new technologies in behavioral health. The collaborative development of global standards along with policies, appropriate regulations, and developing new models of research and development opens the possibility of improved access to care across national boundaries.

Use of antibiotic coated intramedullary nails in open tibia fractures: A European medical resource use and cost-effectiveness analysis.

PURPOSE: In patients with open tibial fractures, bone and wound infections are associated with an increased hospital length of stay and higher costs. The infection risk increases with the use of implants. Innovations to reduce this risk include antibiotic-coated implants. This study models whether the use of a gentamicin-coated intramedullary tibial nail is cost-effective for trauma centers managing patients with a high risk of infection. EFFICACY: Absolute infection risk and relative risk reduction, by fracture grade, for antibiotic-coated nails compared to standard nails for patients with open tibial fractures were estimated based on the results of a meta-analysis, which assessed the additional benefit of locally-administered prophylactic antibiotics in open tibia fractures treated with implants. The observed efficacy of antibiotic-coated nails in reducing infections was applied in an economic model. METHODS: The model compared infection rates, inpatient days, theatre usage and costs in high risk patients, with a Gustilo-Anderson (GA) grade III open fracture, for two patient cohorts from a trauma center perspective, with a 1-year time horizon. In one cohort all GAIII patients received a gentamicin-coated nail whilst GAI and GAII patients received a standard nail. All patients in the comparator cohort received a standard nail. Four European trauma centers provided patient-level data (n=193) on inpatient days, procedures and related costs for patients with and without infections. RESULTS: Using the gentamicin-coated nail in patients at high risk of infection (GAIII) was associated with 75% lower rate of infection and cost savings (€477 - €3.263) for all included centers; the higher cost of the implant was offset by savings from fewer infections, inpatient days (-26%) and re-operations (-10%). This result was confirmed by extensive sensitivity analyses. CONCLUSIONS: Analyses demonstrated that infection rates and total costs for in-hospital treatment could be potentially reduced by 75% and up to 15% respectively, by using a gentamicin-coated nail in patients at high risk of infection. Fewer infections, reduced inpatient days and re-operations may be potentially associated with use of antibiotic-coated implants. Results are sensitive to the underlying infection risk, with greatest efficacy and cost-savings when the coated implant is used in high risk patients.

Mepilex Border Sacrum and Heel Dressings for the Prevention of Pressure Ulcers: A NICE Medical Technology Guidance.

Mepilex Border Sacrum and Heel dressings are self-adherent, multilayer foam dressings designed for use on the heel and sacrum aiming to prevent pressure ulcers. The dressings are used in addition to standard care protocols for pressure ulcer prevention. The National Institute for Health and Care Excellence (NICE) selected Mepilex Border Sacrum and Heel dressings for evaluation. The External Assessment Centre (EAC) critiqued the company's submission. Thirteen studies (four randomised controlled trials and nine nonrandomised comparative studies) were included. The majority of studies compared Mepilex Border Sacrum dressings (plus standard care) with standard care alone. Comparative evidence for Mepilex Border Heel dressings was limited. A meta-analysis indicated a non-statistically significant difference in favour of Mepilex Border Sacrum dressings for pressure ulcer incidence [RR 0.51 (95% CI 0.22-1.18)]. The company produced a de novo cost model, which was critiqued by the EAC. After the EAC updated input parameters, cost savings of £19 per patient compared with standard care alone for pressure ulcer prevention were estimated with Mepilex Border dressings predicted to be cost saving in 57% of iterations. The Medical Technologies Advisory Committee reviewed the evidence and judged that, although Mepilex Border Heel and Sacrum dressings have potential to prevent pressure ulcers in people who are considered to be at risk in acute care settings, further evidence is required to address uncertainties around the claimed benefits of the dressings and the incidence of pressure ulcers in an NHS acute-care setting. After a public consultation, NICE published this as Medical Technology Guidance 40.

An assessment of the microbiological quality of lightly cooked food (including sous-vide) at the point of consumption in England.

This observational study aims to investigate the microbiological quality of commercially prepared lightly cooked foods with a major component of food of animal origin and collected as would be served to a consumer. A total of 356 samples were collected from catering (92%), retail (7%) or producers (1%) and all were independent of known incidents of foodborne illness. Using standard methods, all samples were tested for: the presence of Campylobacter spp. and Salmonella spp. and enumerated for levels of, Bacillus spp. including B. cereus, Clostridium perfringens, Listeria spp. including L. monocytogenes, Staphylococcus aureus, Escherichia coli, Enterobacteriacea and aerobic colony count (ACC). Results were interpreted as unsatisfactory, borderline or satisfactory according to the Health Protection Agency guidelines for assessing the microbiological safety of ready-to-eat foods placed on the market. Amongst all samples, 70% were classified as satisfactory, 18% were borderline and 12% were of unsatisfactory microbiological quality. Amongst the unsatisfactory samples, six (2%) were potentially injurious to health due to the presence of: Salmonella spp. (one duck breast); Campylobacter spp. (two duck breast and one chicken liver pâté); L. monocytogenes at 4·3 × 103 cfu (colony-forming units)/g (one duck confit with foie gras ballotin) and C. perfringens at 2·5 × 105 cfu/g (one chicken liver pâté). The remaining unsatisfactory samples were due to high levels of indicator E. coli, Enterobacteriaceae or ACC.

Physician health programmes and malpractice claims: reducing risk through monitoring.

BACKGROUND: Physician health programmes (PHPs) are peer-assistance organizations that provide support to physicians struggling with addiction or with physical or mental health challenges. While the services they offer are setting new standards for recovery and care, they are not immune to public debate and criticism since some have concerns about those who are enrolled in, or have completed, such programmes and their subsequent ability to practice medicine safely. AIMS: To examine whether medical malpractice claims were associated with monitoring by a PHP using a retrospective examination of administrative data. METHODS: Data on PHP clients who were insured by the largest malpractice carrier in the state were examined. First, a business-model analysis of malpractice risk examined relative risk ratings between programme clients and a matched physician cohort. Second, Wilcoxon analysis examined differences in annual rates of pre- and post-monitoring claims for PHP clients only. RESULTS: Data on 818 clients was available for analysis. After monitoring, those enrolled in the programme showed a 20% lower malpractice risk than the matched cohort. Furthermore physicians' annual rate of claims were significantly lower after programme monitoring among PHP clients (P < 0.01). CONCLUSIONS: This is the only study examining this issue to date. While there are a variety of reasons why physicians present to PHPs, this study demonstrates that treatment and monitoring is associated with a lowered risk of malpractice claims and suggests that patient care may be improved by PHP monitoring.

Characterization of X-ray-generated floral mutants carrying deletions at the S-locus of distylous Turnera subulata.

To investigate the genetic architecture of distyly in Turnera subulata and test the hypothesis that a supergene determines distyly, we used X-ray mutagenesis to generate floral mutants. Based upon the crossing design, all progeny were expected to be short-styled. Of 3982 progeny screened, 10 long-styled mutants, one long homostyle and one short homostyle were recovered. Assays for molecular markers tightly linked to the S-locus showed that the mutants were missing 1-3 markers indicating they are deletion mutants. We investigated the incompatibility phenotype of the mutants and found that both their styles and pollen behaved like those of the long-styled morph. There was a variation in the absolute length of styles, stamens and pollen size of the long-styled mutants. Furthermore, long-styled mutants possessing larger deletions tended to have their anthers and stigmas in closer proximity. We explored the inheritance of the S-locus mutations and found that only one of the deletion mutations was transmitted to progeny where we recovered seven such progeny. Remarkably, our data are consistent with the supergene model (GPA/gpa) of Primula. The long homostyle mutant appears to have deletions involving both the G and P loci. The other mutants appear to have deletions of the entire S-locus. The mutants generated will serve as a valuable resource for the molecular dissection of the S-locus region, and in the identification of genes determining distyly.

Structure of styles and pollen tubes of distylous Turnera joelii and T. scabra (Turneraceae): are there different mechanisms of incompatibility between the morphs?

We investigate the anatomy and fine structure of styles and pollen tubes of two distylous Turnera species, which possess a heteromorphic self-incompatibility system. We use fluorescence and transmission electron microscopy to provide the first description of the cellular aspects of pollen-pistil interactions and ultrastructural changes to pollen tubes during the self-incompatibility response of the morphs. No obvious ultrastructural differences occur between pistils and compatible pollen tubes. Conspicuous differences were, however, observed between incompatible pollen tubes of the morphs. Incompatible pollen tubes of the long-styled morph always appear to be intact, and pollen tube tips are often highly fluorescent when stained with aniline blue, a stain for callose. Swelling and loss of cristae of mitochondria, and circular rough endoplasmic reticulum, were observed for incompatible pollen tubes of the long-styled morph. For incompatible pollen tubes of the short-styled morph, the tube cell wall apex and plasma membrane often appear to be ruptured and no easily recognizable organelles, such as mitochondria, can be discerned. Our results clearly show ultrastructural differences between the morphs and support the hypothesis that different self-incompatibility mechanisms might operate between them.

Assessment of the stability of human viruses and coliphage in groundwater by PCR and infectivity methods.

AIM: To investigate the potential health hazard from infectious viruses where coliphages, or viruses by polymerase chain reaction (PCR), have been detected in groundwater. Two aspects were investigated: the relationship between infectivity and detection by PCR and the stability of coliphage compared to human viruses. METHODS AND RESULTS: Virus decay (1 year) and detection (2 years) studies were undertaken on groundwater at 12 degrees C. The order of virus stability from most to least stable in groundwater, based on first-order inactivation, was: coliphage PhiX174 (0.5 d(-1)) > adenovirus 2 > coliphage PRD1 > poliovirus 3 > coxsackie virus B1 (0.13 d(-1)). The order for PCR results was: norovirus genotype II > adenovirus > norovirus genotype I > enterovirus. CONCLUSIONS: Enterovirus and adenovirus detection by PCR and the duration of infectivity in groundwater followed similar trends over the time period studied. Adenovirus might be a better method for assessing groundwater contamination than using enterovirus; norovirus detection would provide information on a significant human health hazard. Bacteriophage is a good alternative indicator. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR is a useful tool for identifying the health hazard from faecal contamination in groundwater where conditions are conducive to the survival of viruses and their nucleic acid.

Construction of a first genetic map of distylous Turnera and a fine-scale map of the S-locus region.

As a prelude to discovery of genes involved in floral dimorphism and incompatibility, a genetic map of distylous Turnera was constructed along with a fine-scale map of the S-locus region. The genetic map consists of 79 PCR-based molecular markers (48 AFLP, 18 RAPD, 9 ISSR, 4 RAMP), 5 isozyme loci, one additional gene, and the S-locus, spanning a total distance of 683.3 cM. The 86 markers are distributed in 5 linkage groups, corresponding to the haploid chromosome number. Molecular markers tightly linked or co-segregating with the S-locus in an initial mapping population of 94 individuals were used to assay an additional 642 progeny to construct a map of the S-locus region. The fine-scale map consists of 2 markers (IS864a and RP45E9) flanking the S-locus at distances of 0.41 and 0.54 cM, respectively, and 3 additional markers (OPK14c, RP45G18, and RP81E18) co-segregating with the S-locus in the total mapping population of 736 individuals. The genetic map constructed will serve as a framework for localization of genes outside the S-locus affecting distyly, while molecular markers of the fine-scale map will be used to initiate chromosome walking to find the genes residing at the S-locus.

Meiotic recombination in Turnera (Turneraceae): extreme sexual difference in rates, but no evidence for recombination suppression associated with the distyly (S) locus.

To explore the rate of recombination resulting from male vs female meiosis, crosses were performed using distylous Turnera subulata as well as a cross involving the introgression of genes from T. krapovickasii into T. subulata. We assayed four loci on the chromosome bearing the S-locus as well as two loci on each of two other linkage groups. Substantial and consistent dimorphism in recombination rates was found with female meiosis resulting in as much as a approximately 6-fold increase relative to male. Aberrant single locus segregation ratios occurred for some loci, particularly when the male (pollen) parent was heterozygous and the cross involved introgressed genes. The extreme trend of greater recombination resulting from female meiosis was, however, maintained in crosses where no aberrant ratios occurred, indicating that the sex dimorphism in recombination is not the result of aberrant segregation. We also exploited this distylous species and tested whether there is recombination suppression around the S-locus because of an inversion or other chromosome rearrangement(s). We found no significant evidence for recombination suppression.

Inheritance of spontaneous mutant homostyles in Turnera subulata x krapovickasii and in autotetraploid T. scabra (Turneraceae).

To explore the genetic architecture of distyly in Turnera spp., we determined the inheritance and compatibility behaviour of two spontaneous homostyled mutants. A long-homostyled mutant shoot arose on an otherwise short-styled plant that was an artificial hybrid (Turnera subulata x T. krapovickasii) between two diploid distylous species. The mutation appears to be an allele, SH, of the distyly locus with the dominance relationships, S>SH>s, where S confers the short-styled phenotype, SH confers homostyly in SHSH and SHs genotypes, and ss genotypes are long-styled. Aberrant segregation ratios were observed among some crosses and might be the result of pollen competition. Compatibility relationships are consistent with the hypothesis that a gene complex determines distyly. Infrequently, revertant short-styled flowers have appeared on cuttings of the T. subulata x T. krapovickasii mutant and on occasion, short-styled progeny have appeared in crosses where none were expected. A second mutant homostyle was discovered in autotetraploid T. scabra. The mutation is inherited as above, however, tetrasomic inheritance occurs at the locus. This homostyled mutant carries two copies of the SH allele and has the duplex genotype SHSHss. Compatibility relationships were as observed above. The occurrence of homostyled mutants is consistent with the hypothesis that a linked gene complex underlies the inheritance of distyly in Turnera but we cannot discount the hypothesis that an allelic series is responsible.

Distribution of style and pollen polygalacturonases among distylous and homostylous Turnera and Piriqueta spp. (Turneraceae).

We explore the distribution of a style and pollen polygalacturonase in a number of distylous and homostylous species of Turnera, and two species of Piriqueta (Turneraceae). We show, using immunoblotting with antibodies made against these proteins, that the style polygalacturonase is specific to styles of short-styled plants of all the six distylous species of Turnera we have investigated. Styles of a somatic homostylous mutant derived from a short-styled plant do not possess the style polygalacturonase. Distylous P. caroliniana did not appear to possess this protein. We show that the pollen polygalacturonase, while associated with the short-styled morph in three species, is polymorphic among short-styled plants of T. krapovickasii, and absent from T. joelii, T. grandiflora and P. caroliniana. These data support a role for the style polygalacturonase in distyly, possibly in the incompatibility system, but cast doubt on any role for the pollen polygalacturonase. In concert with the predictions for the mode of origin, and the response of styles of homostylous species to pollen from long- and short-styled plants, we find that none of the homostylous species possess the style polygalacturonase. The pollen polygalacturonase does occur in some homostylous species, but not in others. It is not clear that the pollen polygalacturonase, however, provides a marker for the mode of origin of homostyly.

Genetic diversity of the tropical tree Terminalia amazonia (Combretaceae) in naturally fragmented populations.

The effect of long-term fragmentation on the genetic diversity of populations of the neotropical tree species, Terminalia amazonia, was studied using random amplified polymorphic DNA (RAPD) analysis. Leaf material from 104 trees was collected from three naturally fragmented gallery forest patches and three plots in nearby continuous forest in the Mountain Pine Ridge, Belize. In total, 30 RAPD bands generated by five decamer primers were used to compare the genetic diversity of the six populations in the two groups. Genetic variation within the populations (H0), as estimated by the Shannon diversity index, ranged from 0.32 to 0.38, with an overall diversity of 0.38 (Hspecies). Analysis of molecular variation revealed that most (94.4%, P<0.001) of the variation was attributable to differences among individuals within populations. Population differentiation was significantly (P=0.038) lower among the fragmented populations than among continuous forest populations. On average, the fragmented populations also had slightly, but statistically significant (P=0.046) lower levels of genetic diversity. However, one gallery forest site had a higher level of genetic diversity than two of the continuous forest sites. We suggest that the long-term effect of fragmentation on the genetic diversity of tropical trees will depend upon the amount of local forest cover in proximity to the fragmented populations.

Characterization and localization of short-specific polygalacturonase in distylous Turnera subulata (Turneraceae).

We describe for distylous Turnera subulata a polygalacturonase specific to short-styled plants that is localized to the style transmitting tissue (the tissue through which pollen tubes grow). The polygalacturonase gene is linked to and may be upregulated by the S allele of the distyly locus. Because of its tissue-specific location, the polygalacturonase may be involved in the self-incompatibility response, acting in a complementary or antagonistic manner, or possibly in signalling downstream events. A pollen-specific polygalacturonase was also identified and may be a member of a small multigene family of pollen polygalacturonases. The role, if any, played by the pollen polygalacturonase in distyly, is presently unknown.

Resolution of Michaelis complex, acylation, and conformational change steps in the reactions of the serpin, plasminogen activator inhibitor-1, with tissue plasminogen activator and trypsin.

Michaelis complex, acylation, and conformational change steps were resolved in the reactions of the serpin, plasminogen activator inhibitor-1 (PAI-1), with tissue plasminogen activator (tPA) and trypsin by comparing the reactions of active and Ser 195-inactivated enzymes with site-specific fluorescent-labeled PAI-1 derivatives that report these events. Anhydrotrypsin or S195A tPA-induced fluorescence changes in P1'-Cys and P9-Cys PAI-1 variants labeled with the fluorophore, NBD, indicative of a substrate-like interaction of the serpin reactive loop with the proteinase active-site, with the P1' label but not the P9 label perturbing the interactions by 10-60-fold. Rapid kinetic analyses of the labeled PAI-1-inactive enzyme interactions were consistent with a single-step reversible binding process involving no conformational change. Blocking of PAI-1 reactive loop-beta-sheet A interactions through mutation of the P14 Thr --> Arg or annealing a reactive center loop peptide into sheet A did not weaken the binding of the inactive enzymes, suggesting that loop-sheet interactions were unlikely to be induced by the binding. Only active trypsin and tPA induced the characteristic fluorescence changes in the labeled PAI-1 variants previously shown to report acylation and reactive loop-sheet A interactions during the PAI-1-proteinase reaction. Rapid kinetic analyses showed saturation of the reaction rate constant and, in the case of the P1'-labeled PAI-1 reaction, biphasic changes in fluorescence indicative of an intermediate resembling the noncovalent complex on the path to the covalent complex. Indistinguishable K(M) and k(lim) values of approximately 20 microM and 80-90 s(-1) for reaction of the two labeled PAI-1s with trypsin suggested that a diffusion-limited association of PAI-1 and trypsin and rate-limiting acylation step, insensitive to the effects of labeling, controlled covalent complex formation. By contrast, differing values of K(M) of 1.7 and 0.1 microM and of k(lim) of 17 and 2.6 s(-1) for tPA reactions with P1' and P9-labeled PAI-1s, respectively, suggested that tPA-PAI-1 exosite interactions, sensitive to the effects of labeling, promoted a rapid association of PAI-1 and tPA and reversible formation of an acyl-enzyme complex but impeded a rate-limiting burial of the reactive loop leading to trapping of the acyl-enzyme complex. Together, the results suggest a kinetic pathway for formation of the covalent complex between PAI-1 and proteinases involving the initial formation of a Michaelis-type noncovalent complex without significant conformational change, followed by reversible acylation and irreversible reactive loop conformational change steps that trap the proteinase in a covalent complex.

The distal hinge of the reactive site loop and its proximity: a target to modulate plasminogen activator inhibitor-1 activity.

The serpin plasminogen activator inhibitor type 1 (PAI-1) plays a regulatory role in various physiological processes (e.g. fibrinolysis and pericellular proteolysis) and forms a potential target for therapeutic interventions. In this study we identified the epitopes of three PAI-1 inhibitory monoclonal antibodies (MA-44E4, MA-42A2F6, and MA-56A7C10). Differential cross-reactivities of these monoclonals with PAI-1 from different species and sequence alignments between these PAI-1s, combined with the three-dimensional structure, revealed several charged residues as possible candidates to contribute to the respective epitopes. The production, characterization, and subsequent evaluation of a variety of alanine mutants using surface plasmon resonance revealed that the residues His(185), Arg(186), and Arg(187) formed the major sites of interaction for MA-44E4. In contrast, the epitopes of MA-42A2F6 and MA-56A7C10 were found to be conformational. The epitope of MA-42A2F6 comprises residues Lys(243) and Glu(350), whereas the epitope of MA-56A7C10 comprises residues Glu(242), Lys(243), Glu(244), Glu(350), Asp(355), and Arg(356). The participation of Glu(350), Asp(355), and Arg(356) provides a molecular explanation for the differential exposure of this epitope in the different conformations of PAI-1 and for the effect of these antibodies on the kinetics of the formation of the initial PAI-1-proteinase complexes. The localization of the epitopes of MA-44E4, MA42A2F6, and MA-56A7C10 elucidates two previously unidentified molecular mechanisms to modulate PAI-1 activity and opens new perspectives for the rational development of PAI-1 neutralizing compounds.

Niobium-93 MQMAS NMR spectroscopic study of alkali and lead niobates.

93Nb (I = 9/2) multiple-quantum magic-angle spinning (MQMAS) NMR spectra of a series of inorganic niobates have been measured. 93Nb MQMAS spectroscopy yields spectra with typically an order of magnitude higher resolution than that obtainable with 93Nb MAS spectroscopy and 93Nb dynamic-angle spinning (DAS) spectroscopy. For example, the full-width at half-maximums of the 93Nb resonances of LiNbO3 were 9 (MAS), 5.8 (DAS), and 0.7 kHz (MQMAS). Broadening of the 93Nb MAS and DAS spectra is due to the second-order quadrupolar and homonuclear dipolar interactions, respectively. The quadrupolar products (P(O)) and isotropic chemical shifts (delta(iso)) of the 93Nb resonances of LiNbO3, NaNbO3, PbNb2O6, Pb2Nb2O7, Pb3Nb2O8, Pb3Nb4O15, Pb3Nb4O13, and Pb1.83Nb1.71Mg0.29O6.39 were determined from MQMAS spectra and range from 13.6 to 26.8 MHz and from -951 to -1113 ppm, respectively. Resonances with relatively large quadrupolar coupling constants (> 30 MHz) were not observed using MQMAS spectroscopy, but were detected using nutation spectroscopy. The applicability and limitations of MQMAS spectroscopy in studying inorganic niobates containing multiple 93Nb resonances are addressed and compared with those of MAS, nutation, and DAS spectroscopies.