Early hypophosphatemia in critically ill children and the effect of parenteral nutrition: A secondary analysis of the PEPaNIC RCT.

BACKGROUND & AIMS: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness. METHODS: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used. RESULTS: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI -3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = -0.002 (95% CI -0.002; -0.001). CONCLUSIONS: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH.

Parental experiences of children with developmental dysplasia of the hip: a qualitative study.

OBJECTIVE: The aim of this qualitative study was to explore the experiences of Dutch parents of children with developmental dysplasia of the hip (DDH), treated with a Pavlik harness, during the diagnostic and treatment process in the first year of life. DESIGN: A qualitative study by means of semistructured interviews was conducted between September and December 2020. Qualitative content analysis was applied to code, categorise and thematise data. SETTING: A large, tertiary referral centre for paediatric orthopaedics in the Netherlands. PARTICIPANTS: A purposive sample of parents of children aged younger than 1 year, who were treated for DDH with a Pavlik harness, were interviewed until data saturation was achieved. A total of 20 interviews with 22 parents were conducted. RESULTS: Five main themes emerged: (1) positive experiences with professionals and peers, (2) insufficient information, (3) treatment concerns, (4) difficulties parenting and (5) emotional burden. Most prominent features that resonated across the interviews which led to insecurity by parents were: insufficient pre-hospital information, unfiltered online information and the lack of overview of the patient journey. CONCLUSION: This study offers novel insights into parental experiences in DDH care. Parents were generally satisfied with DDH care provided by the hospital. The biggest challenges were to cope with (1) insufficient and unfiltered information, (2) the lack of patient journey overview and (3) practical problems and emotional doubts, which led to concerns during treatment. Future research and interventions should focus on optimising information provision and guidance with practical and emotional support for parents of children with DDH.

Observational and experimental studies on sleep duration and aggression: A systematic review and meta-analysis.

Short sleep duration has been linked to higher levels of aggression. To synthetize all available research on this association, a systematic review and meta-analysis was performed. We included observational and experimental studies, using various measures of sleep duration and aggression. Eighty eligible papers were identified, describing 82 studies comprising a total number of 76.761 participants. Meta-analysis of results was possible for 60 studies. Pooled observational results on the association between sleep duration and aggression showed a correlation estimate of -0.16 (95%CI -0.19, -0.12; I2 = 83.9%) and an odds ratio estimate of 1.83 (95%CI 1.47, 2.28; I2 = 0.0%). For experimental studies, the pooled Standardized Mean Difference after manipulation of sleep duration was -0.37 (95%CI -0.80, 0.05; I2 = 89.05%) for controlled designs and -0.34 (95%CI -0.54, -0.14; I2 = 89.05%) for pre-post designs. Effect estimates were stronger for individuals with psychological vulnerabilities and younger persons. Exclusion of studies with low methodological quality strengthened the effect estimate in experimental but not in observational studies. To conclude, short sleep duration is associated with higher levels of aggression, with observational research strongly supporting the association and experimental studies providing mixed results. More well-designed prospective and experimental studies are needed to establish causality and optimize treatment, especially for individuals with psychological vulnerabilities.

General practitioners' attitudes towards opioids for non-cancer pain: a qualitative systematic review.

OBJECTIVES: Worldwide the use of opioids, both doctor-prescribed and illicit, has increased. In most countries, opioids are first prescribed by general practitioners (GPs). Identifying factors that influence GPs' opioid prescription decision-making may help reduce opioid misuse and overuse. We performed a systematic review to gain insight into GP attitudes towards opioid prescription and to identify possible solutions to promote changes in the field of primary care. DESIGN AND SETTING: Systematic review of qualitative studies reporting GPs' attitudes towards opioid use in non-cancer pain management. METHODS: We searched Embase, Medline, Web of Science Core Collection, Cochrane, PsychInfo, Cumulative Index to Nursing & Allied Health Literature (CINAHL) and Google Scholar. Two independent reviewers selected studies based on prespecified eligibility criteria. Study quality was evaluated with the Critical Appraisal Skills Programme checklist, and their results were analysed using thematic analysis. Quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation-Confidence in the Evidence from Reviews of Qualitative research approach. RESULTS: We included 14 studies. Four themes were established using thematic analyses: (1) GPs caught in the middle of 'the opioid crisis'; (2) Are opioids always bad? (3) GPs' weighing scale, taking patient-related and therapeutic relationship-related factors into account; and (4) GPs' sense of powerlessness-lack of alternatives, support by specialists and lack of time in justifying non-prescriptions. CONCLUSION: GP attitudes towards opioid prescribing for non-cancer pain are subject to several GP-related, patient-related and therapeutic relationship-related factors. Raising GP and patient awareness on the inefficacy of opioids in chronic non-cancer pain management and providing non-opioid alternatives to treat chronic pain might help to promote opioid reduction in primary care. More research is needed to develop practical guidelines on appropriate opioid prescribing, tapering off opioid use and adopting effective communication strategies. PROSPERO REGISTRATION NUMBER: CRD42020194561.Cite Now.

Satisfaction, functional outcomes and predictors in hip arthroscopy: a cohort study.

INTRODUCTION: Hip arthroscopy is not always successful, leading to high rates of total hip arthroplasty (THA) after arthroscopy. The aim of this study was to identify risk factors for THA, revision arthroscopy and low patient satisfaction and to compare outcomes of the different procedures of primary hip arthroscopy. METHODS: A total of 91 primary hip arthroscopy procedures in 90 patients (66% female) were analysed. Data were gathered from patient files and a questionnaire was sent to patients including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), modified Harris Hip Score (mHHS), the EuroQol 5-dimension and questions about return to sports, satisfaction and pain before and after surgery. Using regression analyses, predictive factors for the outcomes were identified. RESULTS: After a mean of 1.6 years, 4 patients (4%) underwent revision arthroscopy and 10 (11%) a THA. Of the responders (62%), 66% of the patients was satisfied to very satisfied about the surgery. Mean mHHS score was 75.3 (SE 1.9) and the mean WOMAC score was 81.0 (SE 2.8). Return to sports rate was 58%. A higher age was a significant predictor for lower satisfaction (p = 0.008) and a longer duration of symptoms was a significant predictor for worse mHHS outcome scores (p = 0.005). CONCLUSION: A higher age is a predictor for a lower satisfaction and a longer duration of symptoms before surgery has a negative influence on functional outcome. No risk factors for THA or revision arthroscopy were found and there were no significant differences in outcome measurements between the performed surgeries.

Is reflection like soap? a critical narrative umbrella review of approaches to reflection in medical education research.

Reflection is a complex concept in medical education research. No consensus exists on what reflection exactly entails; thus far, cross-comparing empirical findings has not resulted in definite evidence on how to foster reflection. The concept is as slippery as soap. This leaves the research field with the question, 'how can research approach the conceptual indeterminacy of reflection to produce knowledge?'. The authors conducted a critical narrative umbrella review of research on reflection in medical education. Forty-seven review studies on reflection research from 2000 onwards were reviewed. The authors used the foundational literature on reflection from Dewey and Schön as an analytical lens to identify and critically juxtapose common approaches in reflection research that tackle the conceptual complexity. Research on reflection must deal with the paradox that every conceptualization of reflection is either too sharp or too broad because it is entrenched in practice. The key to conceptualizing reflection lies in its use and purpose, which can be provided by in situ research of reflective practices.

[Impact of the coronavirus on Dutch oral health care and practice]. / Impact van het coronavirus op de praktijkvoering van de Nederlandse mondzorg.

Among dental hygienists and dentists in the Netherlands, the impact of the SARS-CoV-2 pandemic on oral healthcare practices from March to July 2020 was investigated. Of the 1,700 healthcare providers approached, 433 completed questionnaires could be used. The results show that the pandemic has had a profound impact on both the accessibility of oral healthcare and on care provided in oral healthcare practices. Extra attention was paid to hygiene and infection prevention: the types of personal protective equipment and the protocols and procedures were adjusted by many oral healthcare providers. The confirmed prevalence of oral healthcare providers with COVID-19 in this study was 1.6%. However, testing was not available to all respondents with complaints during this initial period. Over half of the respondents estimated that even with additional measures there is an increased risk of infection to oral healthcare providers during their work. The efficacy of the various additional measures in oral healthcare practices related to COVID-19 is still unknown.

Systematic review and meta-analysis of measurement properties of the Hip disability and Osteoarthritis Outcome Score - Physical Function Shortform (HOOS-PS) and the Knee Injury and Osteoarthritis Outcome Score - Physical Function Shortform (KOOS-PS).

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate all evidence on measurement properties of the Hip disability and Osteoarthritis Outcome Score - Physical function Shortform (HOOS-PS) and the Knee Injury and Osteoarthritis Outcome Score - Physical function Shortform (KOOS-PS). DESIGN: This study was conducted according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews of PROMs. MEDLINE, EMBASE, The Cochrane Library, CINAHL and PsychINFO through February 2019 were searched. Eligible studies evaluated patients with hip or knee complaints and described a measurement property, interpretability, feasibility, or the development of either the HOOS-PS or KOOS-PS. RESULTS: Twenty-three studies were included. For both questionnaires, the content validity was found inconsistent and the quality evidence was moderate for a sufficient reliability and high for an insufficient construct validity. The HOOS-PS had a high quality evidence of sufficient structural validity and internal consistency (pooled Cronbach's alpha 0.80; n = 3761) and low quality evidence of sufficient measurement error and indeterminate responsiveness. Concerning the KOOS-PS, the quality evidence was high for an insufficient responsiveness, moderate for an inconsistent structural validity and internal consistency and low for an inconsistent measurement error. CONCLUSIONS: The inconsistent evidence for content validity implies that scores on the HOOS-PS and KOOS-PS may inadequately reflect physical functioning. Furthermore, there is evidence for insufficient construct validity and responsiveness in patients with knee osteoarthritis receiving conservative treatment. Using the HOOS-PS or KOOS-PS as outcome measurement instruments for comparing outcomes, measuring improvements or benchmarking in patients with hip or knee complaints or undergoing arthroplasty should only be done with great caution. REVIEW REGISTRATION: PROSPERO number CRD42017069539.

Patient characteristics do not predict the change in physical functioning following arthroplasty measured by the HOOS-PS and KOOS-PS.

Predicting personalized outcome after arthroplasty improves shared decision-making. The aim of this paper was to determine predictors of functional outcome measured by the Hip disability and Osteoarthritis Outcome Score - Physical function Shortform (HOOS-PS) or Knee injury and Osteoarthritis Outcome Score - Physical function Shortform (KOOS-PS) in patients undergoing total hip (n = 79) or total knee arthroplasty (n = 90) respectively. Patients were assessed at baseline and following arthroplasty. A multiple regression analysis showed that the included variables predicted the change score in HOOS-PS limited (F (8,66) = 3.139, p = 0.005, adjusted R2 = 0.188) and the KOOS-PS not significantly (F (8,73) = 0.837, p = 0.573, adjusted R 2  = -0.016). Concluding, baseline characteristics cannot be used for personalized prediction using the KOOS-PS and HOOS-PS.

[Sleep: the basis of a healthy lifestyle]. / Slaap: de basis voor een gezonde leefstijl.

BACKGROUND: The use of sleep as modifiable lifestyle factor is not yet self-evident in psychiatry.
AIM: To increase knowledge about sleep as health-affecting factor.
METHOD: Description of normal sleep, effects of disturbed sleep and lifestyle advice to promote healthy sleep.
RESULTS: Disturbed sleep negatively impacts physical and mental health. Targeted lifestyle advice can improve sleep and bring about positive effects in multiple areas.
CONCLUSION: From preventive and treatment perspectives, interventions optimizing sleep in psychiatric care seem promising.

Poor sleep quality at baseline is associated with increased aggression over one year in forensic psychiatric patients.

OBJECTIVE: In forensic psychiatric patients, sleep problems as well as impulsivity and aggression are highly prevalent, yet studies on their association over time are lacking. This study investigates the association between sleep quality and changes in impulsivity and aggression in forensic psychiatric patients over one year. METHODS: Data were drawn from an ongoing prospective observational study in adult forensic psychiatric patients admitted to a forensic treatment facility between October 2006 and January 2018. Validated self-reports and observational instruments were used to assess sleep quality, impulsivity and aggression upon admission to the hospital and after one year. Linear regression analyses were performed to examine the association between sleep quality, impulsivity and aggression. All models were adjusted for baseline values of outcome measures, demographic features and general psychopathology. RESULTS: Data from 83 men (age 37.7 ± 11.7 years) with completed consecutive measurements were analyzed. Poor sleep quality was associated with increased self-reported aggression (ß = 1.08; 95% CI, 0.38-1.78). This association was positively confounded by general psychopathology, indicating that sleep quality is specifically related to self-reported aggression instead of being part of general psychopathology (adjusted ß = 1.18; 95% CI, 0.39-1.97). Poor sleep quality was not associated with changes in self-reported impulsivity, clinician-rated impulsivity or clinician-rated hostility in this population. CONCLUSION: Poor sleep quality was associated with an increase in self-reported aggression over one year in male forensic psychiatric patients. Early evaluation and treatment of sleep problems in (forensic) psychiatric patients may play an important role in reducing the risk of aggressive behavior.

Synovial chondromatosis of the hip, a case report and literature review.

A case of giant synovial chondromatosis of the hip with extra-articular localisation in the ileopectineal bursa is presented and the literature concerning this condition is reviewed. Synovial chondromatosis is a rare condition of unknown aetiology. A literature search was performed to identify studies describing outcome after surgical treatment of synovial chondromatosis of the hip. Thirteen studies including two hundred-ninety patients could be included. Mean follow-up was fifty-six months. Seven out of two hundred-ninety developed a complication after surgical resection of the lesion. Recurrence rate of synovial chondromatosis is about 19%. Malignant transformation of synovial chondromatosis to chondrosarcoma is extremely rare. No wound infections were reported and avascular necrosis of the femoral head occurred in one patient who was treated with dislocation of the hip during surgery. After resection of synovial chondromatosis excellent functional outcome can be expected.

In-line UV spectroscopy for the quantification of low-dose active ingredients during the manufacturing of pharmaceutical semi-solid and liquid formulations.

UltraViolet (UV) spectroscopy was evaluated as an innovative Process Analytical Technology (PAT) - tool for the in-line and real-time quantitative determination of low-dosed active pharmaceutical ingredients (APIs) in a semi-solid (gel) and a liquid (suspension) pharmaceutical formulation during their batch production process. The performance of this new PAT-tool (i.e., UV spectroscopy) was compared with an already more established PAT-method based on Raman spectroscopy. In-line UV measurements were carried out with an immersion probe while for the Raman measurements a non-contact PhAT probe was used. For both studied formulations, an in-line API quantification model was developed and validated per spectroscopic technique. The known API concentrations (Y) were correlated with the corresponding in-line collected preprocessed spectra (X) through a Partial Least Squares (PLS) regression. Each developed quantification method was validated by calculating the accuracy profile on the basis of the validation experiments. Furthermore, the measurement uncertainty was determined based on the data generated for the determination of the accuracy profiles. From the accuracy profile of the UV- and Raman-based quantification method for the gel, it was concluded that at the target API concentration of 2% (w/w), 95 out of 100 future routine measurements given by the Raman method will not deviate more than 10% (relative error) from the true API concentration, whereas for the UV method the acceptance limits of 10% were exceeded. For the liquid formulation, the Raman method was not able to quantify the API in the low-dosed suspension (0.09% (w/w) API). In contrast, the in-line UV method was able to adequately quantify the API in the suspension. This study demonstrated that UV spectroscopy can be adopted as a novel in-line PAT-technique for low-dose quantification purposes in pharmaceutical processes. Important is that none of the two spectroscopic techniques was superior to the other for both formulations: the Raman method was more accurate in quantifying the API in the gel (2% (w/w) API), while the UV method performed better for API quantification in the suspension (0.09% (w/w) API).

REducing STEroids in Relapsing Nephrotic syndrome: the RESTERN study- protocol of a national, double-blind, randomised, placebo-controlled, non-inferiority intervention study.

INTRODUCTION: Oral corticosteroids are the first-line treatment for idiopathic childhood nephrotic syndrome. Most children experience several relapses, needing repeated courses of corticosteroid therapy. This exposes them to side effects and long-term complications. For most patients, long-term prognosis is for complete resolution of the disease over time and maintenance of normal kidney function. Therefore, it is vital to focus on minimising adverse events of the disease and its therapy. Unfortunately, no randomised controlled trials are available to determine the optimal corticosteroid treatment of an infrequent relapse of nephrotic syndrome. Recent studies show that treatment schedules for the first episode can safely be shortened to 2 months. The hypothesis of the REducing STEroids in Relapsing Nephrotic syndrome (RESTERN) study is that a 4-week reduction of alternate-day steroids after inducing remission is effective and safe, reduces steroid exposure by 35% on average and is therefore preferable. METHODS AND ANALYSIS: The RESTERN study is a nationwide, double-blind, randomised, placebo-controlled, non-inferiority intervention study. Children aged 1-18 years with a relapse of steroid-sensitive nephrotic syndrome are eligible for this study. Study subjects (n=144) will be randomly assigned to either current standard therapy in the Netherlands or a reduced prednisolone schedule. The primary outcome of the RESTERN study is the time to first relapse after the final prednisolone dose. The secondary outcomes are the number or relapses, progression to frequent relapsing or steroid dependent nephrotic syndrome and the cumulative dosage of prednisolone during the study period. ETHICS AND DISSEMINATION: This non-inferiority trial will be performed in accordance with the Declaration of Helsinki and has been approved by the medical ethical committee of Arnhem-Nijmegen and the Dutch Competent Authority (Central Committee on Research Involving Human Subjects, CCMO). After completion of this study, results will be published in national and international peer-reviewed scientific journals. Papers will be published according to CCMO guidelines. The final report will be made available to trial participants. TRIAL REGISTRATION NUMBER: NTR5670, EudraCT no 2016-002430-76.

HIV testing week 2015: lowering barriers for HIV testing among high-risk groups in Amsterdam.

BACKGROUND: Evaluation of the HIV Testing Week (HTW) 2015 in Amsterdam: the number of (positive) tested persons, characteristics and testing history of the tested population, the differences in attendance per location and the healthcare workers' experiences and opinions concerning the HTW. METHODS: The HTW took place from 28 November till 4 December 2015. Anonymous HIV rapid testing (INSTI™ HIV1/HIV2 Ab test or Determine™ HIV-1/2 Ag/Ab test) was offered free of charge at four hospitals, 12 general practitioner (GP) clinics, a sexually transmitted infections (STI) clinic, a laboratory, sites of a community-based organisation, and at outreach locations. Home-based testing (OraQuick® In-Home HIV Test) was offered online. The focus was to motivate two groups to test: men who have sex with men (MSM) and non-Western migrants. Questionnaires regarding participant's characteristics and HIV testing history were collected. Also healthcare workers were asked to complete a questionnaire evaluating the HTW. RESULTS: In total, 1231 participants were tested. With three positive HIV tests, the detection rate was 0.3% (95%CI 0.26-0.37). Of all participants, 24.7% (304/1231) were MSM. Respectively, 22.3% (275/1231) and 15.7% (193/1231) were first- and second-generation migrants from a non-Western country. Altogether, 56.7% (698/1231) of participants belonged to one of the targeted risk groups. For 32.7% (402/1231) of participants, it was the first time they received testing, and 35.1% (432/1231) were tested more than 1 year ago. Among MSM 13.2% were tested for the first time, among first- and second-generation non-Western migrants this percentage was significantly higher at 27.2% and 33.5% respectively (p < 0.01). The number of tested participants per location varied widely, especially between GP clinics (range 3-63). Healthcare workers were positive about the HTW: about half (46.2%) stated they would more readily offer an HIV test following their experience with the HTW. CONCLUSIONS: This was the first time the Amsterdam HTW was organised on such a large scale. The majority of the tested population belonged to one of the targeted risk groups and received testing either for the first time or for the first time in over a year. It is important to further build upon the experiences of the HTW and offer free of charge low-threshold HIV testing more structurally. An evaluation of cost-effectiveness is also warranted for future editions of the HTW.

Poor Sleep and Its Relation to Impulsivity in Patients with Antisocial or Borderline Personality Disorders.

Studies investigating sleep and personality disorders consistently demonstrate a relation between personality disorders characterized by behavioral disinhibition and/or emotional dysregulation (traditionally termed cluster B personality disorders) and poor sleep. This finding is in line with previous studies associating insomnia with impulsive behavior, since this is a core characteristic of both antisocial and borderline personality disorder. The current study investigates a group (n = 112) of forensic psychiatric inpatients with antisocial or borderline personality disorder or traits thereof. Subjective sleep characteristics and impulsivity were assessed with the Pittsburgh Sleep Quality Index, the Sleep Diagnosis List, and the Barratt Impulsiveness Scale, respectively. More than half of the patients (53.6%) report poor sleep quality and 22.3% appears to suffer from severe chronic insomnia. Both poor sleep quality and chronic insomnia are significantly associated with self-reported impulsivity, in particular with attentional impulsiveness. This association was not significantly influenced by comorbid disorders. Actively treating sleep problems in these patients may not only improve sleep quality, mental health, and physical well-being, but may also have impact on impulsivity-related health risks by increasing self-control.

Harvesting the photoexcited holes on a photocatalytic proton reduction metal-organic framework.

The highly porous titanium based metal-organic framework NH2-MIL-125(Ti) has recently attracted significant attention in the field of photocatalysis as a promising material for H+ reduction. This work reveals charge transfer upon visible light illumination from this MOF to two different charge acceptors, as an alternative to sacrificial electron donors. Charge transfer is demonstrated through a combined spectroscopic study between this MOF and: (1) 2-(1H-pyrazol-3-yl)phenol, a molecule that functionally mimics the tyrosine-histidine pair, responsible for shuttling the holes to the oxygen evolving centre in natural photosynthesis, and (2) TEMPO, a well known and stable radical. Charge transfer of the holes from the MOF to these occluded molecules takes place on the picosecond time scale. This work suggests that, by coupling a stable and recyclable charge acceptor to the photogenerated holes, the charges can be utilised for oxidation reactions and, thus, link the reduction to the oxidation reactions in water splitting.

The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.

BACKGROUND: Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately. METHODS: In the Netherlands Chlamydia Cohort Study (NECCST), a cohort of women of reproductive age with and without a history of CT-infection is followed over a minimum of ten years to investigate (CT-related) reproductive tract complications. This study is a follow-up of the Chlamydia Screening Implementation (CSI) study, executed between 2008 and 2011 in the Netherlands. For NECCST, female CSI participants who consented to be approached for follow-up studies (n = 14,685) are invited, and prospectively followed until 2022. Four data collection moments are foreseen every two consecutive years. Questionnaire data and blood samples for CT-Immunoglobulin G (IgG) measurement are obtained as well as host DNA to determine specific genetic biomarkers related to susceptibility and severity of infection. CT-history will be based on CSI test outcomes, self-reported infections and CT-IgG presence. Information on (time to) pregnancies and the potential long-term complications (i.e. PID, ectopic pregnancy and (tubal factor) subfertility), will be acquired by questionnaires. Reported subfertility will be verified in medical registers. Occurrence of these late complications and prolonged time to pregnancy, as a proxy for reduced fertility due to a previous CT-infection, or other risk factors, will be investigated using longitudinal statistical procedures. DISCUSSION: In the proposed study, the occurrence of late complications following CT-infection and its risk factors will be assessed. Ultimately, provided reliable risk factors and/or markers can be identified for such late complications. This will contribute to the development of a prognostic tool to estimate the risk of CT-related complications at an early time point, enabling targeted prevention and care towards women at risk for late complications. TRIAL REGISTRATION: Dutch Trial Register NTR-5597 . Retrospectively registered 14 February 2016.

Candida albicans alters the bacterial microbiome of early in vitro oral biofilms.

The yeast Candida albicans is an oral commensal microorganism, occurring in the oral cavity of 50-70% of healthy individuals. Its effect on oral ecology has mostly been studied using dual-species models, which disregards the complex nature of oral biofilms. The aim of this study was to culture C. albicans in a complex model to study its effect on oral biofilms. Biofilms, inoculated using pooled stimulated saliva with or without addition of C. albicans, were grown under anaerobic, aerobic, or aerobic +5% CO2 conditions. Red autofluorescence was quantified using a spectrophotometer and visualized in fluorescence photographs. The microbiome of 5 h biofilms was determined using 16S rDNA sequencing. C. albicans was only able to proliferate in biofilms grown under aerobic conditions. After 48 h, C. albicans did not induce differences in total biofilm formation, lactic acid accumulation (cariogenic phenotype) or protease activity (periodontitis phenotype). In vitro, anaerobically grown biofilms developed red autofluorescence, irrespective of inoculum. However, under aerobic conditions, only C. albicans-containing biofilms showed red autofluorescence. Facultative or strict anaerobic Veillonella, Prevotella, Leptotrichia, and Fusobacterium genera were significantly more abundant in biofilms with C. albicans. Biofilms without C. albicans contained more of the aerobic and facultative anaerobic genera Neisseria, Rothia, and Streptococcus. The presence of C. albicans alters the bacterial microbiome in early in vitro oral biofilms, resulting in the presence of strictly anaerobic bacteria under oxygen-rich conditions. This in vitro study illustrates that C. albicans should not be disregarded in healthy oral ecosystems, as it has the potential to influence bacteria significantly.

Ethnic and regional differences in STI clinic use: a Dutch epidemiological study using aggregated STI clinic data combined with population numbers.

OBJECTIVES: Ethnic minorities (EM) from STI-endemic countries are at increased risk to acquire an STI. The objectives of this study were to investigate the difference in STI clinic consultation and positivity rates between ethnic groups, and compare findings between Dutch cities. METHODS: Aggregated population numbers from 2011 to 2013 of 15-44 year-old citizens of Amsterdam, Rotterdam, The Hague and Utrecht extracted from the population register (N=3 129 941 person-years) were combined with aggregated STI clinic consultation data in these cities from the national STI surveillance database (N=113 536). Using negative binomial regression analyses (adjusted for age and gender), we compared STI consultation and positivity rates between ethnic groups and cities. RESULTS: Compared with ethnic Dutch (consultation rate: 40.3/1000 person-years), EM from Eastern Europe, Sub-Sahara Africa, Suriname, the Netherlands Antilles/Aruba and Latin America had higher consultation rates (range relative risk (RR): 1.27-2.26), whereas EM from Turkey, North Africa, Asia and Western countries had lower consultation rates (range RR: 0.29-0.82). Of the consultations among ethnic Dutch, 12.2% was STI positive. Positivity rates were higher among all EM groups (range RR: 1.14-1.81). Consultation rates were highest in Amsterdam and lowest in Utrecht independent of ethnic background (range RR Amsterdam vs Utrecht: 4.30-10.30). Positivity rates differed less between cities. CONCLUSIONS: There were substantial differences in STI clinic use between ethnic groups and cities in the Netherlands. Although higher positivity rates among EM suggest that these high-risk individuals reach STI clinics, it remains unknown whether their reach is optimal. Special attention should be given to EM with comparatively low consultation rates.