Impact of age on pneumococcal colonization of the nasopharynx and oral cavity: an ecological perspective.

Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based ß-diversity (dissimilarity) and ß-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults. Bacterial culture rates from nasopharyngeal samples were used to characterize age-related differences in rates of colonizing bacteria. Dissimilarity in pneumococcal serotype composition was low among saliva and nasopharyngeal samples from children. In contrast, respiratory samples from adults exhibited high serotype dissimilarity, which predominantly consisted of abundance gradients and was associated with reduced nasopharyngeal colonization. Age-related serotype dissimilarity was high among nasopharyngeal samples and relatively low for saliva samples. Reduced nasopharyngeal colonization by pneumococcal serotypes coincided with significantly reduced Moraxella catarrhalis and Haemophilus influenzae and increased Staphylococcus aureus nasopharyngeal colonization rates among adults. Findings from this study suggest that within-host environmental conditions, utilized in the upper airways by pneumococcus and other bacteria, undergo age-related changes. It may result in a host-driven ecological succession of bacterial species colonizing the nasopharynx and lead to competitive exclusion of pneumococcus from the nasopharynx but not from the oral habitat. This explains the poor performance of nasopharyngeal samples for pneumococcal carriage among adults and indicates that in adults saliva more accurately represents the epidemiology of pneumococcal carriage than nasopharyngeal samples.

Impact of geriatric co-management on outcomes in hospitalised cardiology patients aged 85 and over.

OBJECTIVE: Cardiovascular disease and frailty are common among the population aged 85+. We hypothesised these patients might benefit from geriatric co-management, as has been shown in other frail patient populations. However, there is limited evidence supporting geriatric co-management in older, hospitalised cardiology patients. METHODS: A retrospective cohort study was performed in a large teaching hospital in the Netherlands. We compared patients aged 85 and over admitted to the cardiology ward before (control group) and after the implementation of standard geriatric co-management (intervention group). Data on readmission, mortality, length of stay, number of consultations, delirium, and falls were analysed. RESULTS: The data of 1163 patients were analysed (n = 542 control, n = 621 intervention). In the intervention group, 251 patients did not receive the intervention because of logistic reasons or the treating physician's decision. Baseline characteristics were comparable in the intervention and control groups. Patients in the intervention group had a shorter length of stay (-1 day, p = 0.01) and were more often discharged to a geriatric rehabilitation facility (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.10-3.54, p = 0.02) compared with the control patients. Other outcomes were not significantly different between the groups. CONCLUSIONS: After implementation of standard geriatric co-management for hospitalised cardiology patients aged 85 and over, the length of hospital stay shortened and the number of patients discharged to a geriatric rehabilitation facility increased. The adherence to geriatric team recommendations was high. Geriatric co-management would appear to optimise care for older hospitalised patients with cardiac disease.

Polyethylene thickness does not influence aseptic revision rate with highly cross-linked liners in THA with 36-mm femoral heads.

BACKGROUND: To reduce the risk of dislocation, larger head size can be used in total hip arthroplasty (THA). However, larger head size leads to thinner acetabular liners. With conventional polyethylene, thickness of >8 mm has been advocated to reduce stress and wear rate of the polyethylene. Modern polyethylene has become more wear-resistant. In this study, we investigated if the thickness of sequentially cross-linked polyethylene (XLPE) liners is associated with failure of THA in the medium term. PATIENTS AND METHODS: 3654 THAs were included (2009-2016), in which THA was performed with a XLPE liner in combination with a 36-mm femoral head. Patient and surgical characteristics were collected. We compared implant survival of THA with thin liners (<7.9 mm) and thick liners (⩾7.9 mm) with a Kaplan Meier survival analysis at 5 years, median follow-up and 10 years of follow-up with and point aseptic loosening and performed a multivariate analysis to estimate hazard ratios (HR). RESULTS: Median follow-up was 7.7 years (IQR 5.6-9.8). In total, 179 revision procedures were performed, where 82 revisions (46%) were performed for aseptic loosening. The survival rate at 5 years, median and 10 years of follow-up showed no statistically significant difference in implant survival. The survival rate at 10 years follow-up was for thin liners 97.1% (95% CI, 96.3-97.9) and for thick liners 98.2% (95% CI, 97.4-99.0) in the aseptic loosening group (chi-square 2.55; p = 0.11).The adjusted HR for thick liners (⩾7.9 mm) was 0.65 (95% CI, 0.38-1.08) compared with the thin liners (<7.9 mm), which was not significantly different. CONCLUSIONS: From this single-centre retrospective study it appears that thinner polyethylene liners are well tolerated when using second-generation highly cross-linked polyethylene. Thickness of the XLPE liners did not influence the risk of aseptic loosening of the implants in the medium term.

Meningococcal carriage in children and young adults: a cross-sectional and longitudinal study, Iceland, 2019 to 2021.

BackgroundNeisseria meningitidis is a commensal bacterium which can cause invasive disease. Colonisation studies are important to guide vaccination strategies.AimThe study's aim was to determine the prevalence of meningococcal colonisation, duration of carriage and distribution of genogroups in Iceland.MethodsWe collected samples from 1 to 6-year-old children, 15-16-year-old adolescents and 18-20-year-old young adults. Carriers were sampled at regular intervals until the first negative swab. Conventional culture methods and qPCR were applied to detect meningococci and determine the genogroup. Whole genome sequencing was done on groupable meningococci.ResultsNo meningococci were detected among 460 children, while one of 197 (0.5%) adolescents and 34 of 525 young adults (6.5 %) carried meningococci. Non-groupable meningococci were most common (62/77 isolates from 26/35 carriers), followed by genogroup B (MenB) (12/77 isolates from 6/35 carriers). Genogroup Y was detected in two individuals and genogroup W in one. None carried genogroup C (MenC). The longest duration of carriage was at least 21 months. Serial samples from persistent carriers were closely related in WGS.ConclusionsCarriage of pathogenic meningococci is rare in young Icelanders. Non-groupable meningococci were the most common colonising meningococci in Iceland, followed by MenB. No MenC were found. Whole genome sequencing suggests prolonged carriage of the same strains in persistent carriers.

Surveillance of Neisseria meningitidis carriage four years after menACWY vaccine implementation in the Netherlands reveals decline in vaccine-type and rise in genogroup e circulation.

Carriage of Neisseria meningitidisis an accepted endpoint in monitoring meningococcal vaccine effects. We applied molecular methods to assess the impact of menACWY vaccine implementation on meningococcal carriage and genogroup-specific prevalence in young adults in Fall of 2022, four years after the introduction of the tetravalent vaccine in the Netherlands. The overall carriage rate of genogroupable meningococci was not significantly different compared to a pre-menACWY cohort investigated in 2018 (20.8 % or 125 of 601 versus 17.4 % or 52 of 299 individuals, p = 0.25). Of 125 carriers of genogroupable meningococci, 122 (97.6 %) were positive for either vaccine-types menC, menW, menY or genogroups, menB, menE, and menX, which are not targeted by the menACWY vaccine. Compared with a pre-vaccine-implementation cohort, there was 3.8-fold reduction (p < 0.001) in vaccine-type carriage rates and 9.0-fold increase (p < 0.0001) in non-vaccine type menE prevalence. We observe a reduction in menW and menY and an increase in menE, which suggest that implementation of menACWY vaccine affected carriage.

A spitting image: molecular diagnostics applied to saliva enhance detection of Streptococcus pneumoniae and pneumococcal serotype carriage.

Background: Despite strong historical records on the accuracy of saliva testing, oral fluids are considered poorly suited for pneumococcal carriage detection. We evaluated an approach for carriage surveillance and vaccine studies that increases the sensitivity and specificity of pneumococcus and pneumococcal serotype detection in saliva samples. Methods: Quantitative PCR (qPCR)-based methods were applied to detect pneumococcus and pneumococcal serotypes in 971 saliva samples collected from 653 toddlers and 318 adults. Results were compared with culture-based and qPCR-based detection in nasopharyngeal samples collected from children and in nasopharyngeal and oropharyngeal samples collected from adults. Optimal C q cut-offs for positivity in qPCRs were determined via receiver operating characteristic curve analysis and accuracy of different approaches was assessed using a composite reference for pneumococcal and for serotype carriage based on isolation of live pneumococcus from the person or positivity of saliva samples determined with qPCR. To evaluate the inter-laboratory reproducibility of the method, 229 culture-enriched samples were tested independently in the second center. Results: In total, 51.5% of saliva samples from children and 31.8% of saliva samples from adults were positive for pneumococcus. Detection of pneumococcus by qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to diagnostic culture of nasopharyngeal samples in children (Cohen's κ: 0.69-0.79 vs. 0.61-0.73) and in adults (κ: 0.84-0.95 vs. 0.04-0.33) and culture of oropharyngeal samples in adults (κ: 0.84-0.95 vs. -0.12-0.19). Similarly, detection of serotypes with qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to nasopharyngeal culture in children (κ: 0.73-0.82 vs. 0.61-0.73) and adults (κ: 0.90-0.96 vs. 0.00-0.30) and oropharyngeal culture in adults (κ: 0.90-0.96 vs. -0.13 to 0.30). However, results of qPCRs targeting serotype 4, 5, and 17F and serogroups 9, 12, and 35 were excluded due to assays' lack of specificity. We observed excellent quantitative agreement for qPCR-based detection of pneumococcus between laboratories. After exclusion of serotype/serogroup-specific assays with insufficient specificity, moderate agreement (κ 0.68, 95% CI 0.58-0.77) was observed. Conclusion: Molecular testing of culture-enriched saliva samples improves the sensitivity of overall surveillance of pneumococcal carriage in children and adults, but limitations of qPCR-based approaches for pneumococcal serotypes carriage detection should be considered.

Streptococcus pneumoniae carriage studies in adults: Importance, challenges, and key issues to consider when using quantitative PCR-based approaches.

Streptococcus pneumoniae causes significant morbidity and mortality among older adults. Detection of pneumococcal carriage is an accepted endpoint in pneumococcal conjugate vaccine studies. However, low sensitivity of culture-based approaches and nasopharyngeal samples have hampered adult S. pneumoniae carriage studies in the past. In contrast, detection of adult S. pneumoniae carriers with qPCR-based approaches can achieve high sensitivity and specificity and qPCR-based testing of oral samples improves accuracy of adult carriage detection. In this Viewpoint we outline a strategy for accurate qPCR-based testing. We recommend a dual-target approach for S. pneumoniae qPCR detection as no genetic target is universally present among or solely unique to it. Furthermore, we advise the evaluation of concordance among quantified qPCR targets to improve the accuracy of S. pneumoniae testing and qPCR-based serotyping. We do not recommend omission of qPCR-based oral sample testing as it will likely result in an underestimation of true adult carrier rates.

Home telemonitoring versus hospital care in complicated pregnancies in the Netherlands: a randomised, controlled non-inferiority trial (HoTeL).

BACKGROUND: Women with complicated pregnancies often require hospital admission. Telemonitoring at home is a promising alternative that fulfils a worldwide need in obstetric health care. Moreover, the COVID-19 pandemic has accelerated the transformation to digital care. The aim of this study was to evaluate safety, clinical effectiveness, patient satisfaction, and costs of home telemonitoring against hospital care in complicated pregnancies. METHODS: We did a multicentre, randomised, controlled, non-inferiority trial in six hospitals (four general teaching hospitals and two university hospitals) in the Netherlands (located in Utrecht, Amsterdam, and Groningen). Women aged 18 years and older with singleton pregnancies (>26 weeks gestation) requiring monitoring for pre-eclampsia, fetal growth restriction, fetal anomaly, preterm rupture of membranes, reduced fetal movements, or history of fetal death were included in the study. Participants were randomly assigned to either hospital admission or telemonitoring in (1:1), stratified for the six diagnoses for inclusion and the six centres of inclusion, using block randomisation (block sizes of four and six). When assigned to telemonitoring, participants went home with devices for cardiotocography and blood pressure measurements and had daily contact with their care providers after digitally sending their home measurements. When assigned to hospital admission, participants received care as usual on the ward until the postpartum period. The primary outcome was a composite of adverse perinatal outcomes assessed after delivery, including mortality; an Apgar score below 7 after 5 min or an umbilical arterial pH at birth below 7·05; maternal morbidity; admission of the newborn to the neonatal intensive care unit; and rate of caesarean section. The primary outcome was assessed in the intention-to-treat population. The non-inferiority margin for the primary outcome was a 10% absolute increase in composite primary endpoint based on baseline 20% incidence. The study was registered at the Dutch Trial Registration (NL5888) and is now closed to new participants. FINDINGS: From Dec 1, 2016, to Nov 30, 2019, 201 pregnant women were randomly assigned to an intervention procedure. 101 women were allocated to the telemonitoring group and 100 to the hospital admission group. One participant in the telemonitoring group withdrew consent before the intervention was initiated, and 100 participants were analysed for the primary outcome. In the hospital admission group, four participants did not receive the allocated intervention because they did not accept hospital admission. 100 participants in each group were analysed for the primary outcome according to the intention-to-treat principal. No participants were lost to follow-up. The primary outcome occurred in 31 (31%) of 100 participants in the telemonitoring group and in 40 (40%) of 100 participants in the hospital admission group. Adjusted for centre of inclusion, diagnosis, and nulliparity, the risk difference in primary outcome between both groups was 10·3% (95% CI -22·4 to 2·2) lower in the telemonitoring group, below the pre-defined non-inferiority margin of 10% absolute increase. A similar distribution for each of the individual components within the composite primary outcome was seen between groups. Five serious adverse events were reported: one neonatal death in the hospital admission group, in addition to one intra-uterine fetal death, two neonatal deaths, and one case of eclampsia in the telemonitoring group, all unrelated to the study. INTERPRETATION: This non-inferiority trial shows the first evidence that telemonitoring might be as safe as hospital admission for monitoring complicated pregnancies. FUNDING: Stichting Achmea Gezondheidszorg and ICT Healthcare Technology Solutions.

Women's migration to cities.

This study investigates the consequences of female rural-urban migration with respect to their education, career, and relationship and family formation in the Netherlands. The study is based on four birth cohorts of Dutch women born in 1970-1973 in rural areas, comparing those who had migrated to urban areas before the age of 25 with those who had remained behind. Outcomes were measured at age 42. The data were derived from administrative registers available at Statistics Netherlands. The results show that female migration to cities served to increase women's resources: they were more often university educated and had better paid jobs, in line with the idea of cities as socioeconomic escalators. The city also functioned as a relationship market with a relative abundance of men with resources. Both lower and university educated city women were more likely to be in a relationship with a highly educated man compared to their rural peers. However, lower educated women had an increased probability of being single at age 42 when they lived in cities at age 25. This was not the case for university educated women. In conclusion, for lower educated women urban migration may entail risks as well as benefits, especially with respect to family formation. University educated women on the other hand benefited both in terms of their own socioeconomic outcomes and in terms of their partners' resources.

Outcome of Cataract Surgery in Patients With Retinitis Pigmentosa.

PURPOSE: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, noncomparative clinical study. METHODS: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe. RESULTS: In total, 295 eyes of 226 patients were included in the study. The mean age at surgery of the first eye was 56.1 ± 17.9 years. Following surgery, best-corrected visual acuity (BCVA) improved significantly from 1.03 to 0.81 logMAR (ie, 20/214 to 20/129 Snellen) in the first treated eye (-0.22 logMAR; 95% CI = -0.31 to -0.13; P < .001) and from 0.80 to 0.56 logMAR (ie, 20/126 to 20/73 Snellen) in the second treated eye (-0.24 logMAR; 95% CI = -0.32 to -0.15; P < .001). Marked BCVA improvements (postoperative change in BCVA of ≥0.3 logMAR) were observed in 87 of 226 patients (39%). Greater odds for marked visual improvements were observed in patients with moderate visual impairment or worse. The most common complications were zonular dialysis (n = 15; 5%) and (exacerbation of) cystoid macular edema (n = 14; 5%), respectively. Postoperative posterior capsular opacifications were present in 111 of 295 eyes (38%). CONCLUSION: Significant improvements in BCVA are observed in most patients with RP following cataract surgery. Baseline BCVA is a predictor of visual outcome. Preoperative evaluation should include the assessment of potential zonular insufficiency and the presence of CME, as they are relatively common and may increase the risk of complications.

Cost-effectiveness of the implementation of [68Ga]Ga-PSMA-11 PET/CT at initial prostate cancer staging.

BACKGROUND: Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40-50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results. METHOD: A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime. RESULTS: The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. CONCLUSION: Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.

Surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures following cardiopulmonary resuscitation: An international, retrospective matched case-control study.

BACKGROUND: The presence of six or more rib fractures or a displaced rib fracture due to cardiopulmonary resuscitation (CPR) has been associated with longer hospital and intensive care unit (ICU) length of stay (LOS). Evidence on the effect of surgical stabilization of rib fractures (SSRF) following CPR is limited. This study aimed to evaluate outcomes after SSRF versus nonoperative management in patients with multiple rib fractures after CPR. METHODS: An international, retrospective study was performed in patients who underwent SSRF or nonoperative management for multiple rib fractures following CPR between January 1, 2012, and July 31, 2020. Patients who underwent SSRF were matched to nonoperative controls by cardiac arrest location and cause, rib fracture pattern, and age. The primary outcome was ICU LOS. RESULTS: Thirty-nine operatively treated patient were matched to 66 nonoperatively managed controls with comparable CPR-related characteristics. Patients who underwent SSRF more often had displaced rib fractures (n = 28 [72%] vs. n = 31 [47%]; p = 0.015) and a higher median number of displaced ribs (2 [P 25 -P 75 , 0-3] vs. 0 [P 25 -P 75 , 0-3]; p = 0.014). Surgical stabilization of rib fractures was performed at a median of 5 days (P 25 -P 75 , 3-8 days) after CPR. In the nonoperative group, a rib fixation specialist was consulted in 14 patients (21%). The ICU LOS was longer in the SSRF group (13 days [P 25 -P 75 , 9-23 days] vs. 9 days [P 25 -P 75 , 5-15 days]; p = 0.004). Mechanical ventilator-free days, hospital LOS, thoracic complications, and mortality were similar. CONCLUSION: Despite matching, those who underwent SSRF over nonoperative management for multiple rib fractures following CPR had more severe consequential chest wall injury and a longer ICU LOS. A benefit of SSRF on in-hospital outcomes could not be demonstrated. A low consultation rate for rib fixation in the nonoperative group indicates that the consideration to perform SSRF in this population might be associated with other nonradiographic or injury-related variables. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

It Takes Two to Tango: Combining Conventional Culture With Molecular Diagnostics Enhances Accuracy of Streptococcus pneumoniae Detection and Pneumococcal Serogroup/Serotype Determination in Carriage.

Background: The specificity of molecular methods for the detection of Streptococcus pneumoniae carriage is under debate. We propose a procedure for carriage surveillance and vaccine impact studies that increases the accuracy of molecular detection of live pneumococci in polymicrobial respiratory samples. Methods: Culture and qPCR methods were applied to detect pneumococcus and pneumococcal serotypes in 1,549 nasopharyngeal samples collected in the Netherlands (n = 972) and England (n = 577) from 946 toddlers and 603 adults, and in paired oropharyngeal samples collected exclusively from 319 Dutch adults. Samples with no live pneumococci isolated at primary diagnostic culture yet generating signal specific for pneumococcus in qPCRs were re-examined with a second, qPCR-guided culture. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic (ROC) curve analysis using isolation of live pneumococci from the primary and qPCR-guided cultures as reference. Results: Detection of pneumococcus and pneumococcal serotypes with qPCRs in cultured (culture-enriched) nasopharyngeal samples exhibited near-perfect agreement with conventional culture (Cohen's kappa: 0.95). Molecular methods displayed increased sensitivity of detection for multiple serotype carriage, and implementation of qPCR-guided culturing significantly increased the proportion of nasopharyngeal and oropharyngeal samples from which live pneumococcus was recovered (p < 0.0001). For paired nasopharyngeal and oropharyngeal samples from adults none of the methods applied to a single sample type exhibited good agreement with results for primary and qPCR-guided nasopharyngeal and oropharyngeal cultures combined (Cohens kappa; 0.13-0.55). However, molecular detection of pneumococcus displayed increased sensitivity with culture-enriched oropharyngeal samples when compared with either nasopharyngeal or oropharyngeal primary cultures (p < 0.05). Conclusion: The accuracy of pneumococcal carriage surveillance can be greatly improved by complementing conventional culture with qPCR and vice versa, by using results of conventional and qPCR-guided cultures to interpret qPCR data. The specificity of molecular methods for the detection of live pneumococci can be enhanced by incorporating statistical procedures based on ROC curve analysis. The procedure we propose for future carriage surveillance and vaccine impact studies improves detection of pneumococcal carriage in adults in particular and enhances the specificity of serotype carriage detection.

Clinical outcomes of treatment with idebenone in Leber's hereditary optic neuropathy in the Netherlands: A national cohort study.

PURPOSE: The purpose of the study was to present results from a national Dutch cohort of patients with Leber's Hereditary Optic Neuropathy (LHON) treated with idebenone. METHODS: The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment. RESULTS: Data from 72 patients were analysed. Treatment duration was 23.8 ± 14.4 (mean ± SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 ± 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced. CONCLUSION: Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent.

High Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission Rates Detected by Dense Saliva Sampling.

BACKGROUND: Understanding the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission is important for adequate infection control measures in this ongoing pandemic. METHODS: Households were enrolled upon a polymerase chain reaction-confirmed index case between October and December 2020, prior to the coronavirus disease 2019 vaccination program. Saliva samples were obtained by self-sampling at days 1, 3, 5, 7, 10, 14, 21, 28, 35, and 42 from study inclusion. Nasopharyngeal swabs (NPS) and oropharyngeal swabs (OPS) were collected by the research team at day 7 and capillary blood samples at day 42. Household secondary attack rate (SAR) and per-person SAR were calculated based on at least 1 positive saliva, NPS, OPS, or serum sample. Whole genome sequencing was performed to investigate the possibility of multiple independent SARS-CoV-2 introductions within a household. RESULTS: Eighty-five households were included consisting of 326 (unvaccinated) individuals. Comparable numbers of secondary cases were identified by saliva (133/241 [55.2%]) and serum (127/213 [59.6%]). The household SAR was 88.2%. The per-person SAR was 64.3%. The majority of the secondary cases tested positive in saliva at day 1 (103/150 [68.7%]). Transmission from index case to household member was not affected by age or the nature of their relationship. Phylogenetic analyses suggested a single introduction for the investigated households. CONCLUSIONS: Households have a pivotal role in SARS-CoV-2 transmission. By repeated saliva self-sampling combined with NPS, OPS, and serology, we found the highest SARS-CoV-2 household transmission rates reported to date. Salivary (self-) sampling of adults and children is suitable and attractive for near real-time monitoring of SARS-CoV-2 transmission in this setting.

Medical costs of children admitted to the neonatal intensive care unit: The role and possible economic impact of WES in early diagnosis.

It has been estimated that at least 6.0% of neonates admitted to the Neonatal Intensive Care Unit remains genetically undiagnosed because genetic testing is not routinely performed. The objective of this study is to provide an overview of average healthcare costs for patients admitted to the Neonatal Intensive Care Unit and to assess possible impact of implementing Whole Exome Sequencing (WES) on these total healthcare costs. Hereto, we retrospectively collected postnatal healthcare data of all patients admitted to the level IV Neonatal Intensive Care Unit at the Radboudumc (October 2013-October 2015) and linked unit costs to these healthcare consumptions. Average healthcare costs were calculated and a distinction between patients was made based on performance of genetic tests and the presence of congenital anomalies. Overall, on average €26,627 was spent per patient. Genetic costs accounted for 2.3% of all costs. Healthcare costs were higher for patients with congenital anomalies compared to patients without congenital anomalies. Patients with genetic diagnostics were also more expensive than patients without genetic diagnostics. We next modelled four scenarios based on clinical preselection. First, when performing trio-WES for all patients instead of current diagnostics, overall healthcare costs will increase with 22.2%. Second, performing trio-WES only for patients with multiple congenital anomalies will not result in any cost changes, but this would leave patients with an isolated congenital anomalies untested. We therefore next modelled a scenario performing trio-WES for all patients with congenital anomalies, increasing the average per patient healthcare costs by 5.3%. This will rise to a maximum of 5.5% when also modelling for an extra genetic test for clinically selected patients to establish genetic diagnoses that are undetectable by WES. In conclusion, genetic diagnostic testing accounted for a small fraction of total costs. Implementation of trio-WES as first-tier test for all patients with congenital anomalies will lead to a limited increase in overall healthcare budget, but will facilitate personalized treatments options guided by the diagnoses made.

Multidimensional outcome assessment of pulmonary rehabilitation in traits-based clusters of COPD patients.

BACKGROUND: Clusters of COPD patients have been reported in order to individualize the treatment program. Neither co-morbidity clusters, nor integrated respiratory physiomics clusters contributed to a better prediction of outcomes. Based on a thoroughly assessed set of pulmonary and extra-pulmonary traits at the start of a pulmonary rehabilitation (PR) program, we recently described seven clusters of COPD patients. The aims of this study are to confirm multidimensional differential response and to assess the potential of pulmonary and extra-pulmonary traits-based clusters to predict this multidimensional response to PR pulmonary in COPD patients. METHODS: Outcomes of a 40-session PR program for COPD patients, referred by a chest physician, were evaluated based on the minimal clinically important difference (MCID) for 6-minute walk distance (6MWD), cycle endurance time, Canadian Occupational Performance Measure performance and satisfaction scores, Hospital Anxiety and Depression Scale anxiety and depression scores, MRC dyspnea grade and St George's Respiratory Questionnaire. The aforementioned response indicators were used to calculate the overall multidimensional response and patients were grouped in very good, good, moderate and poor responders. In the same way, responses to pulmonary rehabilitation were compared based on seven previously identified pulmonary and extra-pulmonary traits-based clusters. RESULTS: Of the whole sample, drop out was 19% and 419 patients (55.4% males, age: 64.3 ± 8.8, FEV1% of predicted: 48.9 ± 20) completed the pulmonary rehabilitation program. Very good responders had significantly worse baseline characteristics with a higher burden of disease, a higher proportion of rollator-users, higher body mass index (BMI), more limitations of activities in daily life, emotional dysfunction, higher symptoms of dyspnea and worse quality of life. Of the seven pre-identified clusters, 'the overall best functioning cluster' and 'the low disease burden cluster' both including the best 6MWD, the lowest dyspnea score and the overall best health status, demonstrated attenuated outcomes, while in 'the cluster of disabled patients', 76% of the patients improved health status with at least 2 times MCID. This 'cluster of disabled patients' as well as 'the multimorbid cluster', 'the emotionally dysfunctioning cluster', 'the overall worst-functioning cluster' and 'the physically dysfunctioning cluster' all demonstrated improvements in performance and satisfaction for occupational activities (more than 65% of patients improved with > 1MCID), emotional functioning (more than 50% of patients improved with > 1 MCID) and overall health status (more than 58%). CONCLUSION: The current study confirms the differential response to pulmonary rehabilitation based on multidimensional response profiling. Cluster analysis of baseline traits illustrates that non-linear, clinically important differences can be achieved in the most functionally and emotionally impaired clusters and that 'the overall best functional cluster' as well as 'the low disease burden cluster' had an attenuated outcome.

Impact of upper blepharoplasty, with or without orbicularis oculi muscle removal, on tear film dynamics and dry eye symptoms: A randomized controlled trial.

PURPOSE: Upper blepharoplasty may be related to dry eye symptoms since the function of the orbicularis oculi muscle may affect the tear film. We aimed to assess the effect of blepharoplasty with or without the removal of a strip of orbicularis oculi muscle on tear film dynamics and dry eye symptoms. METHODS: A double-blind, randomized, controlled trial comparing upper blepharoplasty without (group A) or with (group B) orbicularis oculi muscle excision was performed on 54 healthy Caucasian patients. Tear film dynamics and dry eye symptoms were evaluated using multiple dry eye parameters, i.e. tear osmolarity, Schirmer test I, corneal/conjunctival staining, tear break-up time (TBUT), Oxford Scheme, Sicca Ocular Staining Score and Ocular Surface Disease Index questionnaire. All the parameters were assessed preoperatively and 6 and 12 months after upper blepharoplasty. All the groups' outcomes were compared. RESULTS: The differences were not significant between the two upper blepharoplasty techniques regarding most of the above-mentioned outcomes. Subjective symptoms of ocular irritation, consistent with dry eye disease and vision-related impairment, were reduced after upper blepharoplasty independent of the type of the technique applied, while the pre and postoperative outcomes of the objective tear dynamics did not differ 12 months after surgery. However, group B demonstrated a significant increase in tear osmolarity and TBUT at the 6-month follow-up visit. CONCLUSION: An upper blepharoplasty alleviates subjective dry eye complaints in the long term, while not changing the tear dynamics. The improvement was independent of the blepharoplasty technique used.

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry.

PURPOSE: To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases. METHODS: For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry. RESULTS: A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1. CONCLUSION: The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention.

Detection of Neisseria meningitidis in saliva and oropharyngeal samples from college students.

Carriage of Neisseria meningitidis is an accepted endpoint in monitoring meningococcal vaccines effects. We have assessed N. meningitidis and vaccine-type genogroup carriage prevalence in college students at the time of MenACWY vaccine introduction in the Netherlands, and evaluated the feasibility of saliva sampling for the surveillance of carriage. For this, paired saliva and oropharyngeal samples collected from 299 students were cultured for meningococcus. The DNA extracted from all bacterial growth was subjected to qPCRs quantifying meningococcal and genogroup-specific genes presence. Samples negative by culture yet positive for qPCR were cultured again for meningococcus. Altogether 74 (25%) of students were identified as meningococcal carrier by any method. Sixty-one students (20%) were identified as carriers with qPCR. The difference between number of qPCR-positive oropharyngeal (n = 59) and saliva (n = 52) samples was not significant (McNemar's test, p = 0.07). Meningococci were cultured from 72 students (24%), with a significantly higher (p < 0.001) number of oropharyngeal (n = 70) compared with saliva (n = 54) samples. The prevalence of genogroups A, B, C, W, and Y was none, 9%, 1%, 1% and 6%, respectively, and 8% of students carried MenACWY vaccine-type genogroup meningococci. Saliva is easy to collect and when combined with qPCR detection can be considered for meningococcal carriage studies.