Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

BACKGROUND: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus. AIM: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe. METHODS: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls. FINDINGS: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis. CONCLUSION: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden.

Benefits of a 14-year surgical site infections active surveillance programme in a French teaching hospital.

BACKGROUND: Surgical site infections (SSIs) are the second most common healthcare-associated infection. Active SSI surveillance can help inform preventative measures and assess the impact of these measures. AIM: We aimed to describe the evolution in trends over 14 years of prospective active SSI surveillance and implementations of SSI prevention measures in a French Teaching Hospital. METHODS: We monitored and included in the study all surgical procedures performed from 2003 to 2016 in eight surgical units. The semi-automated surveillance method consisted of weekly collection of SSI declaration forms (pre-filled with patient and procedure administrative data and microbiology laboratory data), filled-in by surgeons and then monitored by the infection control practitioners. FINDINGS: A total of 181,746 procedures were included in our analysis and 3270 SSIs recorded (global SSI rate 1.8%). The SSI rate decreased significantly from 3.0% in 2003 to 1.1% in 2016. This decrease was mainly in superficial SSIs and high infectious risk procedures. Higher SSI rates were observed for procedures associated with the usual risk factors. During this 14-year period, several evolutions in surgical practices occurred that might have contributed to this decrease. CONCLUSIONS: With an overall decrease in SSI rate throughout the surveillance, our results revealed the benefits of an active and comprehensive hospital SSI surveillance programme for understanding the SSI rate trends, analysing local risk factors and assessing the effectiveness of prevention strategies. These findings also highlighted the importance of the collaboration between surgeons and infection control practitioners.

Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Epstein-Barr virus (EBV) is associated with a number of different human tumors and appears to play different pathogenetic roles in each case. Thus, immunoblastic B cell lymphomas of the immunosuppressed display the full pattern of EBV latent gene expression (expressing Epstein-Barr nuclear antigen [EBNA]1, 2, 3A, 3B, 3C, and -LP, and latent membrane protein [LMP]1, 2A, and 2B), just as do B lymphoblastoid cell lines transformed by the virus in vitro. In contrast, those EBV-associated tumors with a more complex, multistep pathogenesis show more restricted patterns of viral gene expression, limited in Burkitt's lymphoma to EBNA1 only and in nasopharyngeal carcinoma (NPC) to EBNA1 and LMP1, 2A, and 2B. Recent evidence has implicated EBV in the pathogenesis of another lymphoid tumor, Hodgkin's disease (HD), where the malignant Hodgkin's and Reed-Sternberg (HRS) cells are EBV genome positive in up to 50% of cases. Here we extend preliminary results on viral gene expression in HRS cells by adopting polymerase chain reaction-based and in situ hybridization assays capable of detecting specific EBV latent transcripts diagnostic of the different possible forms of EBV latency. We show that the transcriptional program of the virus in HRS cells is similar to that seen in NPC in several respects: (a) selective expression of EBNA1 mRNA from the BamHI F promoter; (b) downregulation of the BamHI C and W promoters and their associated EBNA mRNAs; (c) expression of LMP1 and, in most cases, LMP2A and 2B transcripts; and (d) expression of the "rightward-running" BamHI A transcripts once thought to be unique to NPC. This form of latency, consistently detected in EBV-positive HD irrespective of histological subtype, implies an active role for the virus in the pathogenesis of HD and also suggests that the tumor may remain sensitive to at least certain facets of the EBV-induced cytotoxic T cell response.

Standardized patient methodology to assess refractive error reproducibility.

PURPOSE: Standardized patient (SP) methodology is the gold standard for evaluating clinical practice. This approach was used to investigate the content of typical optometric eyecare in England and the reproducibility of refractive error measurement using prescriptions obtained by three SPs. METHODS: The three SPs were independently examined by three to four expert optometric clinicians to obtain "benchmark" estimates of refractive error. One hundred two community optometrists consented to be visited by three SPs who were trained to provide accurate responses during the examinations. The spectacle prescriptions obtained by the SPs were analyzed for spherical equivalent refraction, spherical power and cylindrical power using astigmatic decomposition. RESULTS: The spherical equivalent refractions were found to be within +/-0.25 D of the benchmark on average 81% of the time and within +/-0.50 D 97% of the time. The spherical power was within +/-0.25 D 90% of the time and within +/-0.50 D 98% of the time. The cylindrical power agreed within +/-0.25 D 93% of the time and within +/-0.50 D 100% of the time. Based on reproducibility limits data obtained for all six eyes, any two optometrists would differ in their estimation of spherical equivalent refraction by no more than 0.75 D in 95% of repeated measures. The astigmatic data (C0 and C45) show that optometrists will differ in their estimation of the C0 component by between 0.25 and 0.61 D and for the C45 component by between 0.22 and 0.47 D in 95% of repeated measures. CONCLUSIONS: The agreement between our data and the results of other similar studies support the conclusions that subjective refractive findings are reproducible to approximately +/-0.75 D when performed by multiple optometrists in patients of different age groups and levels of ametropia. SPs are an effective way of measuring reproducibility of refractive error and should be considered for further comparative analysis in different age groups and different levels of ametropia.

The content of optometric eye examinations for a presbyopic patient presenting with symptoms of flashing lights.

BACKGROUND: Standardised patients (SPs) are the gold standard methodology for evaluating clinical care. This approach was used to investigate the content of optometric eyecare for a presbyopic patient who presented with recent photopsia. METHODS: A total of 102 community optometrists consented to be visited by an actor for a recorded eye examination. This actor received extensive training to enable accurate reporting of the content of the eye examinations, via an audio recording and a checklist completed for each clinical encounter. The actor presented unannounced (incognito) as a 59-year-old patient seeking a private eye examination and complaining of recent onset flashing lights. The results of each clinical encounter were recorded on a pre-designed checklist based on evidence-based reviews on photopsia, clinical guidelines and the views of an expert panel. RESULTS: The presence of the symptom of photopsia was proactively detected in 87% of cases. Although none of the optometrists visited asked all seven gold standard questions relating to the presenting symptoms of flashing lights, 35% asked four of the seven questions. A total of 85% of optometrists asked the patient if he noticed any floaters in his vision and 36% of optometrists asked if he had noticed any shadows in his vision. The proportion of the tests recommended by the expert panel that were carried out varied from 33 to 100% with a mean of 67%. Specifically, 66% recommended dilated fundoscopy to be carried out either by themselves or by another eyecare practitioner, and 29% of optometrists asked the patient to seek a second opinion regarding the photopsia. Of those who referred, 70% asked for the referral to be on the same day or within a week. CONCLUSION: SP encounters are an effective way of measuring clinical care within optometry and should be considered for further comparative measurements of quality of care. As in research using SPs in other healthcare disciplines, our study has highlighted substantial differences between different practitioners in the duration and depth of their clinical investigations. This highlights the fact that not all eye examinations are the same but inherently different and that there is no such thing as a 'standard sight test'. Future optometric continuing education could focus on history taking, examination techniques and referral guidelines for patients presenting with symptoms of posterior vitreous detachment, retinal breaks and secondary retinal detachment.

Staphylococcus Aureus Carriage in French Athletes at Risk of CA-MRSA Infection: a Prospective, Cross-sectional Study.

BACKGROUND: Staphylococcus aureus (SA) is a leading cause of infectious diseases in sports teams. In recent decades, community-associated SA (CA-SA) strains have emerged worldwide and have been responsible for outbreaks in sports teams. There are very few data on the prevalence of these strains in France, and none on the carriage among athletes. METHODS: We conducted a cross-sectional study to determine the SA carriage proportion among athletes practicing sports at risk for CA-SA infection in a French county, and determined the methicillin-resistant and/or CA-SA proportion. We also analyzed SA carriage according to risks factors and studied the SA clonality in a sample of our population. RESULTS: We included 300 athletes; SA carriage proportion was 61% (n = 183) and one was MRSA carrier (0.33%). The MRSA strain belonged to the clonal complex ST5. None of the strain produced Panton Valentine Leucocidin, and we did not find clonal distribution within the teams. Interestingly, we found a high throat-only carriage (n = 57), 31.1% of the SA carriers. CONCLUSION: We found a high SA carriage with a local epidemiology quite different than that reported in a similar population in the USA. Further studies on SA carriage should include throat sampling. TRIAL REGISTRATION: The approved protocol was registered on ClinicalTrial.gov , NCT01148485.

PKC-delta is an apoptotic lamin kinase.

Protein kinase C-delta is activated during apoptosis, following proteolytic cleavage by caspase 3. Furthermore, overexpression of the catalytic kinase fragment of PKC-delta induces the nuclear phenotype associated with apoptosis, though the molecular basis of this effect has not been determined. In these studies we have examined the role of PKC-delta in the disassembly of the nuclear lamina at apoptosis. The nuclear lamina is disassembled during mitosis and apoptosis and mitotic disassembly involves hyperphosphorylation of lamin proteins by mitotic lamin kinases. During apoptosis, lamin proteins are degraded by caspase 6 and the contribution made by phosphorylation has not been proven. We show here that protein kinase C-delta co-localized with lamin B during apoptosis and activation of PKC-delta by caspase 3 was concomitant with lamin B phosphorylation and proteolysis. Inhibition of PKC-delta delayed lamin proteolysis, even in the presence of active caspase 6, whilst inhibitors of mitotic lamin kinases were without effect. In addition recombinant human PKC-delta was able to phosphorylate lamin B in vitro suggesting that its actions are direct and not via an intermediary kinase. We propose that PKC-delta is an apoptotic lamin kinase and that efficient lamina disassembly at apoptosis requires both lamin hyperphosphorylation and caspase mediated proteolysis.

Murine p53 is phosphorylated within the PAb421 epitope by protein kinase C in vitro, but not in vivo, even after stimulation with the phorbol ester o-tetradecanoylphorbol 13-acetate.

The p53 tumour suppressor protein is thought to play a major role in the defence of the cell against agents which damage DNA. p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro. In this report, we have examined the phosphorylation of murine p53 by protein kinase C (PKC). Phosphopeptide mapping, phosphoamino acid analysis and radiosequence analysis of p53 phosphorylated by PKC in vitro indicated that serine 370 and threonine 377 were the major targets for phosphorylation and suggested that serine 372 and threonines 365 and 371 were minor phosphorylation sites. Site-directed mutagenesis confirmed that residues 370-372, all of which lie within the epitope for monoclonal antibody PAb421, were phosphorylated in vitro. The p53 from 32P-labelled SV3T3 cells showed a phosphopeptide pattern which includes peptides with mobilities similar to those arising from phosphorylation of residues 370-372 by PKC in vitro. Only two of these in vivo-labelled phosphopeptides co-migrated in two dimensions with peptides labelled in vitro within the PAb421 epitope and their phosphorylation was not stimulated by the addition of the PKC activator o-tetradecanoylphorbol 13-acetate (TPA) to the cells, even though this treatment led to a fourfold stimulation of p53 phosphorylation by MAP kinase. Moreover, when the p53 proteins containing mutations at residues 370-372 were expressed in COS cells, there was no loss of any of the in vivo phosphopeptides, indicating that phosphorylation within the PAb42I epitope was undetectable in the cell. These data suggest that p53 and PKC may not interact in vivo. The two-dimensional migration pattern of the novel group of peptides is consistent with phosphorylation of previously uncharacterised sites within the central DNA binding region of p53.

Doppa induces cell death but not differentiation of U937 cells: evidence for the involvement of PKC-beta 1 in the regulation of apoptosis.

Recent reports have claimed that activation of protein kinase C (PKC)-beta is sufficient for both differentiation and apoptosis in promyeloid HL60 cells. Phorbol esters which differentially activate PKC isoenzymes in vitro were used to induce differentiation and apoptosis in U937 cells; TPA and Dopp activate all U937 PKC isoenzymes, except PKC-zeta and Doppa activate only PKC-beta l. At concentrations of Doppa below 50 nM, only PKC-beta l was activated by 2 min and apoptosis was induced, but there was no differentiation of cells towards monocytes. TPA (1-25 nM) and Dopp (5-100 nM) activated PKC-alpha, -beta l and-gamma within 2 min and induced differentiation, but only increased apoptosis at the highest concentrations used. Thus, initial activation of PKC-beta l is insufficient for differentiation of U937 cells, but may lead to the induction of apoptosis.

The content of optometric eye examinations for a young myope with headaches.

BACKGROUND: A recent review found standardised patient (SP) methodology to be the gold standard methodology for evaluating clinical care. We used this to investigate the content of optometric eye care for a young myopic patient with headaches suggestive of migraine. METHODS: We recruited 100 community optometrists who consented to be visited by an unannounced actor for an eye examination and to have that eye examination recorded. The actor received extensive training to enable accurate reporting of the content of the eye examinations, via an audio recording and a checklist completed for each clinical encounter. The actor presented as a 20-year-old student seeking a private eye examination and complaining of symptoms suggestive of migraine headaches. The results of each clinical encounter were recorded on a pre-designed checklist based on evidence-based reviews on headaches, clinical guidelines and the views of an expert panel of optometrists. RESULTS: The presence of headache was detected in 98% of cases. Eight standard headache questions were considered to be the gold standard for primary care headache investigation. Although none of the optometrists asked all of these questions, 22% asked at least four of the eight questions. Sixty-nine per cent of practitioners asked the patient to seek a medical opinion regarding the headaches. The proportion of the tests recommended by the expert panel that was carried out varied from 33% to 89% and the durations of the eye examination varied from 5 to 50 min. CONCLUSION: SP encounters are an effective way of measuring clinical care within optometry and should be considered for further comparative measurements of quality of care. As in research using SPs in other healthcare disciplines, our study has highlighted substantial differences between different practitioners in the duration and depth of their clinical investigations. This highlights the fact that not all eye examinations are the same and that there is no such thing as a 'standard sight test'. We recommend that future optometric continuing education could usefully focus on migraine diagnosis and assessment.

Technical Note: A comparison of a novel direct ophthalmoscope, the Optyse, to conventional direct ophthalmoscopes.

Despite the current popularity of binocular indirect ophthalmoscopy, direct ophthalmoscopes are still commonly used by clinicians for fundus examination. They are considered to be expensive, however, and it has been suggested that this cost can prevent their use by healthcare professionals in developing countries. The Optyse Lens Free Ophthalmoscope is a novel direct ophthalmoscope, without a lens focus system, that allows for comparatively inexpensive manufacture and supply. We compared the clarity of view with the Optyse to that with standard direct ophthalmoscopes, over a sequential cohort of patients with a variety of refractive errors and ocular conditions. The grade of clarity of view with the Optyse Lens Free Ophthalmoscope was less than conventional ophthalmoscopes (Wilcoxon signed rank test, p < 0.0001). This grade of clarity of view was not associated with the ametropia of the ophthalmoscopic observation (Spearman r < or = 0.03, p > or = 0.28) but was with the presence of cataracts (chi2 test, p < 0.0001) with both the Optyse and the conventional ophthalmoscopes. Despite its limitations, the retinal view with Optyse was often within acceptable clinical limits suggesting that this relatively inexpensive ophthalmoscope may have a place when cost prohibits any other type of ophthalmoscope use.

Subtle binocular vision anomalies in migraine.

A literature review reveals old references to an association between migraine headache and binocular vision anomalies, but a lack of scientific evidence evaluating these claims. In a masked case control study, we investigated binocular vision using standard clinical tests in people with migraine and in controls. Some test results suggest that heterophoria and fixation disparity are more common in the migraine group. The migraine group also had slightly reduced stereopsis. We found significant correlations between some migraine variables and some binocular vision variables (e.g., duration of worst headache and impaired stereopsis) but our analyses do not suggest that a causal relationship is likely. In conclusion, people with migraine have on average a slightly higher prevalence of heterophoria and aligning prism, and reduced stereopsis compared with controls. However, the differences are subtle and our data do not support the use of binocular vision interventions prescribed solely on the basis of the presence of migraine.

The correlation between migraine headache and refractive errors.

PURPOSE: A literature review reveals historical references to an association between migraine headache and refractive errors, but a lack of scientific evidence relating to these claims. METHODS: In a masked case-controlled study, we investigated the four aspects of refractive errors that have been implicated in the literature as correlated with migraine: spherical refractive error, astigmatic refractive error, anisometropia, and uncorrected ametropia. We also compared the calculated scalar value of refractive error, aided and unaided visual acuity, and spectacle use in migraine and control groups. We then investigated the relationship between refractive components and key migraine headache variables. RESULTS: Compared with the control group, the migraine group had higher degrees of astigmatic components of refractive error assessed both objectively (C, p = 0.01; C(0), p = 0.01; C(45), p = 0.05) and subjectively (C, p = 0.03; C(0), p = 0.03; C(45), p = 0.05), uncorrected astigmatic components of refractive error (C(0), p = 0.02; C(45), p = 0.04), and anisometropia (p = 0.06). CONCLUSIONS: Perhaps the historical literature is indeed correct that low degrees of astigmatism and anisometropia are relevant in migraine. Our most significant finding was of higher degrees of astigmatism in the migraine group. This study does indicate that people who experience migraine headaches should attend their optometrist regularly to ensure that their refractive errors are appropriately corrected.

Visual stimuli are common triggers of migraine and are associated with pattern glare.

OBJECTIVE: To investigate the associations between interictal pattern glare, visual stress, and visual triggers of migraine. BACKGROUND: There has been relatively little research on the visual stimuli that can trigger migraine episodes. This is surprising, since if practitioners can obviate such triggers, then some attacks may be prevented. The existing literature suggests that patients who are prone to visually triggered migraines report more illusions on viewing striped patterns ("pattern glare") and that colored filters may be an effective intervention for these people. METHODS: Headache symptoms and headache triggers were investigated in migraine and control groups in 2 separate experiments. In one experiment, we also determined, for each participant, pattern glare, whether it was reduced by colored filters and, if so, what the optimum color of filter was. Color vision was also assessed with the D15 test. RESULTS: People with migraine saw significantly more illusions on viewing each striped pattern and experienced greater pattern glare. They were also more likely to select a colored filter to aid visual comfort, particularly colors in the blue-to-green sector of the spectrum. Color vision was impaired subtly but significantly in migraine. Principal component analyses grouped common headache triggers into 5 broadly equal components: food, visual triggers, alcohol, stress and tiredness, and the environment. In a second analysis, the overall number of illusions seen in striped patterns was associated with visual triggers while pattern glare, use of colored filters, and interictal light sensitivity together formed a sixth component interpreted as visual stress. CONCLUSIONS: It is suggested that clinicians should ask migraine patients whether visual stimuli trigger their migraine, about interictal visual symptoms, and use the pattern glare test to ensure that those who may benefit from optometric interventions are appropriately managed.

Frequency doubling technology perimetry and standard automated perimetry in migraine.

The literature suggests that visual field defects may be more common in people who experience migraine. The Humphrey frequency doubling (FDT) visual field instrument selectively examines the magnocellular visual pathway, but has not previously been used to investigate visual function in migraine. In a masked controlled study we compared Humphrey FDT and Humphrey Swedish Interactive Threshold Algorithm fields of 25 migraine sufferers with 25 age- and gender-matched controls. Although both mean deviation and pattern standard deviation were a little worse in the migraine group, these differences did not reach statistical significance. There were no inter-eye visual field differences in the migraine group compared with controls. Comparing the mean of all the contrast thresholds in each hemisphere, there were no more inter-hemifield visual field differences in the migraine group compared with controls. There was no significant difference between the migraine and control groups in intra-ocular pressures. The visual field parameters were not correlated with the interval since the last migraine headache, the severity of migraine headache, the duration of migraine headache or the number of migraine headaches per annum. In our data, there was no evidence of visual field deficits, a magnocellular deficit, or indications of glaucomatous pathology.

The pupillary light reflex in migraine.

The literature suggests that there may be pupil size and response abnormalities in migraine headache sufferers. We used an infra-red pupillometer to measure dynamic pupil responses to light in 20 migraine sufferers (during non-headache periods) and 16 non-migraine age and gender matched controls. There was a significant increase in the absolute inter-ocular difference of the latency of the pupil light response in the migraine group compared with the controls (0.062 s vs 0.025 s, p = 0.014). There was also a significant correlation between anisocoria and lateralisation of headache such that migraine sufferers with a habitual head pain side have more anisocoria (r = 0.59, p < 0.01), but this was not related to headache laterality. The pupil changes were not correlated with the interval since the last migraine headache, the severity of migraine headache or the number of migraine headaches per annum. We conclude that subtle sympathetic and parasympathetic pupil abnormalities persist in the inter-ictal phase of migraine.

Plasma cell populations in labial salivary glands from patients with and without Sjögren's syndrome.

Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (n = 25) and compared with glands from patients with a variety of systemic diseases (n = 32) and normal individuals (n = 15). Based on qualitative and quantitative analysis, glands from the systemic disease group were divided into normal histology (n = 24) and non-specific inflammation (n = 8) groups. There were no significant differences in cell densities or Ig class proportions between histologically normal glands from patients and those from normal volunteers. Total immunocyte densities were significantly increased in sialadenitis (P < 0.025) and Sjögren's syndrome (P < 0.001) compared with normal histology glands. In both the sialadenitis and Sjögren's syndrome groups there were significant increases in IgG and IgM cell densities (IgG, P < 0.006; IgM, P < 0.001) and proportions (IgG, P < 0.05; IgM, P < 0.001). There were no significant differences in immunocyte densities or proportions between the sialadenitis and Sjögren's syndrome groups except for a lower percentage proportion of IgA cells in the latter (P < 0.038). In all groups the total and individual Ig-class cell densities showed significant positive correlations with extent of leucocyte infiltration (P < 0.01) and negative correlations between IgA and IgG and/or IgM cell proportions. Analysis of the plasma cell data alone and in combination with quantifiable histological parameters failed to yield specific or sensitive diagnostic information. The results suggest that changes in glandular plasma cell populations in Sjögren's syndrome are non-specific.