Fluoride Use in Health Care Settings: Association with Children's Caries Risk.

Expanded partnership with the medical community is an important strategy for reducing dental caries disparities. The purpose of this study was to assess the relationship between fluoride (F) "in office" (drops/tablets and/or varnish), as prescribed or applied by a health care professional by age 1 y, and 1) caries development and 2) presence of other caries risk factors or mediators (e.g., socioeconomic status). Child-primary caregiver (PCG) pairs ( N = 1,325) were recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort study to validate a caries risk tool for primary health care settings. PCGs completed a caries risk questionnaire, while children received caries examinations per the criteria of the International Caries Detection and Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding children's history of F in office were tested for association with other caries risk variables and caries experience at ages 2.5 and 4 y via generalized estimating equation models applied to logistic regression. The sample was 48% female, and many children (61%) were Medicaid enrolled. The prevalence of cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y. Children who received F in office were likely deemed at higher caries risk and indeed were significantly ( P < 0.01) more likely to develop cavitated caries lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3, respectively). Factors significantly associated with receiving F included the following: child being Medicaid enrolled, not having an employed adult in the household, child and PCG often consuming sugary drinks and snacks, and PCG having recent caries experience. Increased F in office from a health care provider by age 1 y was associated with known caries risk factors. Most (69%) children had never been to the dentist, suggesting that risk factors could be alerting medical providers and/or parents, thereby affecting in-office F recommendations. Differences among states could also be related to state-specific F-varnish reimbursement policies (ClinicalTrials.gov NCT01707797).

Multicentre study of short-course radiotherapy and transanal endoscopic microsurgery for early rectal cancer.

BACKGROUND: Organ-preserving treatment for early-stage rectal cancer may avoid the substantial perioperative morbidity and functional sequelae associated with total mesorectal excision (TME). The initial results of an organ-preserving approach using preoperative short-course radiotherapy (SCRT) and transanal endoscopic microsurgery (TEMS) are presented. METHODS: Patients with cT1-2N0 rectal cancers staged using high-quality MRI and endorectal ultrasonography received SCRT, with TEMS 8-10 weeks later, at four regional referral centres between 2007 and 2013. Patients were generally considered high risk for TME surgery (a small number refused TME). RESULTS: Following SCRT and TEMS, 60 (97 per cent) of 62 patients had an R0 resection. Histopathological staging identified 20 ypT0 tumours, 23 ypT1, 18 ypT2 and one ypT3. Preoperative uT category was significantly associated with a complete pathological response, which was achieved in 13 of 27 patients with uT0/uT1 disease and in five of 29 with uT2 (P = 0·010). Acute complications affected 19 patients, the majority following TEMS. No fistulas occurred and no stomas were formed. Surveillance detected four intraluminal local recurrences at a median follow-up of 13 months, all in patients with tumours staged as ypT2. Salvage TME achieved R0 resection in three patients and a stent was placed in one patient owing to co-morbidities. CONCLUSION: SCRT with TEMS was effective in the majority of patients considered high risk for (or who refused) TME surgery.

QM/MM study of l-lactate oxidation by flavocytochrome b2.

In this work, we have performed molecular dynamics simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) scheme to study the mechanism of l-lactate oxidation by flavocytochrome b2 (Fcb2). Our results obtained at the QM(AM1)/MM level have been improved by single-point corrections using density functional theory (DFT) methods. Free energy surfaces have been calculated in the framework of the hydride transfer hypothesis. This mechanism involves the transfer of the lactate hydroxyl proton to H373 while the substrate αH atom is transferred as a hydride to the flavin mononucleotide (FMN) prosthetic group anchored in the active site. Four different systems have been modeled: wild-type enzyme considering R289 in a distal or a proximal conformation observed in crystal structures and the D282N and Y254L variants (with R289 in a distal position). Simulation results highlight the influence of the environment on the catalytic mechanism by describing a step-wise process in the WT enzyme with R289 in a distal position and a concerted mechanism for the other systems. In the step-wise mechanism, the hydride transfer to flavin can occur only after a proton transfer from substrate to H373. Modifications of the electrostatic field around l-lactate or H373 disfavor the highly charged complex resulting from this proton transfer. Simulations of the Y254L variant also reveal some effect of steric changes.

Outcome of patients with systemic lupus erythematosus on chronic dialysis: an observational study of incident patients of the French National Registry 2002-2012.

OBJECTIVES: The objective of this article is to describe the outcome (mortality, kidney transplantation) of patients with systemic lupus erythematosus (SLE) on chronic dialysis. METHODS: The overall and cardiovascular (CV) mortality and access to kidney transplantation were studied in all SLE patients incident on chronic dialysis in France between 2002 and 2012 (REIN registry). They were compared to age- and sex-matched patients with diabetic nephropathy and with autosomal dominant polycystic kidney disease (PKD) on chronic dialysis. RESULTS: A total of 368 SLE patients were included in the national REIN registry between 2002 and 2012. Cumulative incidence of death was 16.9% at five years, with no difference between haemodialysis and peritoneal dialysis. Independent risk factors of death were age, past history of cardiovascular disease (CVD) and chronic respiratory insufficiency. At five years, CV and all-cause mortality in SLE patients were lower than in matched diabetic patients, but three-fold higher than in matched PKD patients. Access to the kidney transplant waiting list and to kidney transplantation was higher in SLE patients than in matched diabetic patients, but lower than in matched PKD patients. CONCLUSIONS: SLE patients on chronic dialysis are a population at high risk of death influenced by CV burden and chronic respiratory failure, but not by the method of dialysis. Their outcome, in terms of mortality and access to kidney transplantation, is intermediate between diabetic patients and patients with PKD.

Hysteroscopic sterilization: 10-year retrospective analysis of worldwide pregnancy reports.

STUDY OBJECTIVE: To identify factors that might contribute to pregnancies reported after hysteroscopic sterilization worldwide. DESIGN: Retrospective review of commercial data compiled from the MAUDE database, medical literature, and manufacturer reports received during commercial distribution of hysteroscopic sterilization micro-inserts from 2001 through 2010 (Canadian Taskforce classification III descriptive study). MEASUREMENTS AND MAIN RESULTS: From 2001 through 2010, 497 305 hysteroscopic sterilization kits were distributed worldwide, and 748 pregnancies were reported, i.e., 0.15% of the estimated user population based on the number of distributed kits. The data were sufficient to enable analysis of 508 pregnancies for potential contributing factors and showed most to be associated with patient or physician noncompliance (n = 264) or misinterpreted confirmation tests (n = 212). Conceptions deemed to have occurred within 2 weeks of the procedure and therefore too early for detection were identified in 32 cases. CONCLUSION: Although there are limitations to the dataset and the study design is retrospective, it represents the largest body of cumulative hysteroscopic sterilization data available to date. Of the 748 pregnancies reported, it is apparent that some might have been prevented with greater patient and clinician attention to interim contraceptive use and counseling and with more rigorous evaluation and informed interpretation of the procedure confirmation tests. Although the estimated pregnancy rate based on such a dataset is likely an underestimation, it does suggest that the evaluable field performance of hysteroscopic sterilization micro-inserts is consistent with the labeled age-adjusted effectiveness of 99.74% at 5 years.

Transanal endoscopic microsurgery: a new technique for completion proctectomy.

AIM: Following subtotal colectomy, the retained rectal stump is a potential source of morbidity. Although restorative ileal pouch-anal anastomosis is the gold standard for ulcerative colitis, up to 14% of patients will opt for a permanent ileostomy and undergo completion proctectomy, traditionally by an abdomino-perineal approach, which itself carries significant morbidity. We describe a new technique of perineal proctectomy using transanal endoscopic microsurgery (TEMS) equipment. To our knowledge, this technique has not previously been described in the literature. METHOD: Twelve patients, mean (SD) age 66 (±13) years, underwent TEMS proctectomy, performed by a single surgeon between January 2007 and October 2011. Excision began with an intersphincteric dissection following which the TEMS (WOLF) proctoscope was inserted and close rectal dissection was performed, entering the peritoneal cavity (if the top of the stump was intraperitoneal). Following perineal extraction of the specimen, the external sphincter and skin were closed with an absorbable suture. RESULTS: Nine patients had inflammatory bowel disease, two had neoplasia and one had intractable radiation proctitis. The mean (SD) rectal stump length was 17.8 (±6.1) cm and the peritoneal cavity was entered in nine patients, with no small-bowel injury. The median postoperative hospital stay was 5.5 days. In four patients there was delayed healing of the perineal wound. There was no perioperative mortality. CONCLUSION: TEMS perineal proctectomy is a novel, but safe, technique that may avoid the need for a traditional abdominoperineal approach in selected patients.

SkinExplorer: a new high-tech platform to interact inside the skin by immersive virtual 3D cutaneous environment.

BACKGROUND: The confocal laser scanning microscope allows performing acquisition of several histological sections with precise visual morphological landmarks and their reconstruction. A powerful and modern confocal microscope enables to quickly reconstruct virtual 3D models. OBJECTIVE: The main goal was to develop a new platform to reconstruct complex mosaic serial data, interact with it in an immersive 3D environment, and give to the observers a feeling of 'presence' inside the skin. METHOD: We have developed novel methods that transform the data into alternative representation, well-suited to explore cutaneous structures in detail and to observe fields of data from different points of view. This new way of data reconstruction in volume requires optimization of intensities, automatic matching algorithms and depth alignment. RESULTS AND CONCLUSION: The new platform - SkinExplorer evolves as a 3D exploration prototype. This technology provides an immersive virtual environment to explore cutaneous microstructures. Several serial histological sections can be matched by stacks, aligned in depth by sections and merged together to be visualized as a whole. All these time-consuming steps have been dramatically speed-up using rapid image processing. The advantages of using virtual reality technologies such as the ones used in the SkinExplorer platform are automatic matching, precise alignment, better data perception, lower memory requirement, and higher quantity of simultaneously displayed data. This platform can render volumetric data and isosurfaces, separately or both at the same time. Lighting and depth perception are enhanced using 'Sphere Mapping', 'Ambient Occlusion', and 'Halo' methods when displaying iso-surfacic volume models with high complexity depth. The assets of the platform are to interpret complex three-dimensional data, to observe and explore 3D virtual models, and to show effects of cosmetic treatments.

[The impact of early cranioplasty on cerebral blood flow and its correlation with neurological and cognitive outcome. Prospective multi-centre study on 24 patients]. / Impact de la cranioplastie sur l'hémodynamique cérébrale comme facteur pronostic de l'amélioration clinique chez les patients craniectomisés pour traumatisme crânien grave.

INTRODUCTION: Cranioplasty after decompressive craniectomy in patients suffering from severe head injury often leads to a functional improvement although, to date, the pathophysiology of this phenomenon remains unclear. A few hypotheses have been proposed. The impact of cranioplasty on cerebral perfusion could be one explanation. We have evaluated the impact of cranioplasty on the functional status of patients undergoing decompressive craniectomy for severe head injury with its influence on cerebral perfusion. MATERIALS AND METHODS: Twenty-four patients undergoing craniectomy for severe head injury were included in this multi-centric and prospective study. All of them had a cranioplasty within 12 weeks following decompressive craniectomy. A clinical and radiological evaluation was performed prior to and after cranioplasty. Neurological and cognitive evaluation was performed with the Glasgow Outcome Score (GOS), the Frontal Assessment Battery (FAB) and the Mini Mental State Examination (MMSE). Radiological evaluation was performed by perfusion CT scan and transcranial Doppler. RESULTS: A statistically significant neurological and cognitive improvement was observed in 92% of patients at 6 months follow-up (F-U). Brain perfusion was improved at 6 weeks F-U, predominantly in the affected hemisphere. Systolic and diastolic blood velocity flow were improved in both middle cerebral arteries. CONCLUSION: Cranioplasty after decompressive craniectomy for patients suffering from severe head injury probably improves the functional outcome of these patients, thanks to a global improvement of cerebral perfusion.

Predicting Dental Caries in Young Children in Primary Health Care Settings.

Young children need increased access to dental prevention and care. Targeting high caries risk children first helps meet this need. The objective of this study was to develop a parent-completed, easy-to-score, short, accurate caries risk tool for screening in primary health care settings to identify children at increased risk for cavities. A longitudinal, prospective, multisite, cohort study enrolled (primarily through primary health care settings) and followed 985 (out of 1,326) 1-y-old children and their primary caregivers (PCGs) until age 4. The PCG completed a 52-item self-administered questionnaire, and children were examined using the International Caries Detection and Assessment Criteria (ICDAS) at 12 ± 3 mo (baseline), 30 ± 3 mo (80% retention), and 48 ± 3 mo of age (74% retention). Cavitated caries lesion (dmfs = decayed, missing, and filled surfaces; d = ICDAS ≥3) experience at 4 y of age was assessed and tested for associations with questionnaire items using generalized estimating equation models applied to logistic regression. Multivariable analysis used backward model selection, with a limit of 10 items. At age 4, 24% of children had cavitated-level caries experience; 49% were female; 14% were Hispanic, 41% were White, 33% were Black, 2% were other, and 10% were multiracial; 58% enrolled in Medicaid; and 95% lived in urban communities. The age 4 multivariable prediction model, using age 1 responses (area under the receiver operating characteristic curve = 0.73), included the following significant (P < 0.001) variables (odds ratios): child participating in public assistance programs such as Medicaid (1.74), being non-White (1.80-1.96), born premature (1.48), not born by caesarean section (1.28), snacking on sugary snacks (3 or more/d, 2.22; 1-2/d or weekly, 1.55), PCG cleaning the pacifier with juice/soda/honey or sweet drink (2.17), PCG daily sharing/tasting food with child using same spoon/fork/glass (1.32), PCG brushing their teeth less than daily (2.72), PCG's gums bleeding daily when brushing or PCG having no teeth (1.83-2.00), and PCG having cavities/fillings/extractions in past 2 y (1.55). A 10-item caries risk tool at age 1 shows good agreement with cavitated-level caries experience by age 4.

Copy number changes on the X chromosome in women with and without highly skewed X-chromosome inactivation.

AIM: To test the hypothesis that microdeletions or microduplications below the resolution of a standard karyotype may be a significant cause of highly skewed X-inactivation (HSXI) in women without a cytogenetically detected X-chromosome anomaly. METHODS: Cases were women with HSXI, defined as ≥85% of cells in a blood sample with the same active allele at the HUMARA locus. The skewing in controls ranged from 50 to <75%. We performed an SNP microarray analysis using the Affymetrix 6.0 platform for 45 cases and 45 controls. RESULTS: Cases and controls did not differ in the frequency of X-chromosome copy number changes ≥100 kb or in the frequency of copy number changes that contained genes. However, one woman with HSXI >90% in blood and left and right buccal smears had a 5.5-Mb deletion in Xp22.2p22.1. This deletion could affect the viability of male conceptions and may have led to the dysmorphology found in female carriers. CONCLUSION: HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.

Intra-operative oxygen delivery in infusion volume-optimized patients undergoing laparoscopic colorectal surgery within an enhanced recovery programme: the effect of different analgesic modalities.

AIM: Patients undergoing major open surgery who have an indexed oxygen delivery (DO(2) I) > 600 ml/min/m(2) have been shown to have a lower incidence of morbidity and mortality compared with those whose DO(2) I is below this level. Laparoscopy and Trendelenburg positioning cause a reduction in DO(2) I. We aimed to quantify the effect of the type of analgesia on DO(2) I and to correlate the DO(2) I achieved with the incidence of anastomotic leakage in patients undergoing laparoscopic surgery. METHOD: Following ethical approval, patients were randomized to receive spinal anaesthesia (Group S), epidural analgesia (Group E) or intravenous morphine (Group P) followed by postoperative patient-controlled analgesia (PCA). In addition to standard monitoring, oesophageal Doppler monitoring of the stroke volume allowed directed intravenous fluid therapy. The mean DO(2) I was compared with the anastomotic leakage rate. RESULTS: Seventy-five patients were recruited (Group S, 27; Group E, 23; Group P, 25). The mean (range) DO(2) I for all patients was 490 (230-750) ml/min/m(2) . The analgesic modality had no effect on DO(2) I. Of the 18 patients with a DO(2) I of < 400 ml/min/m(2) , four (22%) developed anastomotic leakage compared with one (%) of the 57 patients with a DO(2) I of > 400 ml/min/m(2) (P = 0.01). CONCLUSION: The analgesic modality used had no effect on the DO(2) I achieved. Anastomotic leakage was significantly higher in patients with a DO(2) I of < 400 ml/min/m(2) . A further study assessing the outcome after raising the DO(2) I with inotropes is required.

Identification of novel potential cyclooxygenase-2 inhibitors using ligand- and structure-based virtual screening approaches.

Cyclooxygenase 2 (COX-2) is a well-established target for the design of anti-inflammatory intermediates. Celecoxib was selected as a template molecule to perform ligand-based virtual screening, i.e. to search for structures with similarity in shape and electrostatic potential, with a gradual increase in accuracy through the combined fitting of several steps using eight commercial databases. The molecules ZINC408709 and ZINC2090319 reproduced values within the limits established in an initial study of absorption and distribution in the body. No alert was fired for possible toxic groups when these molecules were subjected to toxicity prediction. Molecular docking results with these compounds showed a higher binding affinity in comparison to rofecoxib for the COX-2 target. Additionally, ZINC408709 and ZINC2090319 were predicted to be potentially biologically active. In in silico prediction of endocrine disruption potential, it was established that the molecule ZINC2090319 binds strongly to the target related to cardiovascular risk in a desirable way as a non-steroidal antagonist and ZINC408709 binds strongly to the target that is associated with the treatment of inflammatory pathologies and similar to celecoxib. Metabolites generated from these compounds are less likely to have side effects. Simulations were used to evaluate the interaction of compounds with COX-1 and COX-2 during 200 ns. Despite the differences, ZINC408709 molecule showed better stability for COX-2 during molecular dynamics simulation. In the calculations of free energy MM/PBSA, the molecule ZINC408709 ΔGbind value has a higher affinity to celecoxib and rofecoxib COX-2. This demonstrates that the selected substances can be considered as promising COX-2 inhibitors. Communicated by Ramaswamy H. Sarma.

Randomized clinical trial of epidural, spinal or patient-controlled analgesia for patients undergoing laparoscopic colorectal surgery.

BACKGROUND: Epidural analgesia is considered fundamental in enhanced recovery protocols (ERPs). However, its value in laparoscopic colorectal surgery is unclear. The aim of this study was to examine the effects of different analgesic regimens on outcomes following laparoscopic colorectal surgery in fluid-optimized patients treated within an ERP. METHODS: Ninety-nine patients were randomized to receive epidural, spinal or patient-controlled (PCA) analgesia. The primary endpoints were time until medically fit for discharge and length of hospital stay. Secondary endpoints included return of bowel function, pain scores, and changes in pulmonary function and quality of life. RESULTS: Ninety-one patients completed the study. The median length of hospital stay was 3.7 days following epidural analgesia, significantly longer than that of 2.7 and 2.8 days for spinal analgesia and PCA respectively (P = 0.002 and P < 0.001). There was also a slower return of bowel function with epidural analgesia than with spinal analgesia and PCA. Epidural analgesia did not offer better preservation of pulmonary function or quality of life, although pain scores were higher in the PCA group in the early postoperative period. CONCLUSION: Many of the outcomes in the epidural analgesia group were significantly worse than those in the spinal analgesia and PCA groups, suggesting that either of these two modalities could replace epidural analgesia.

Health advantage for black women: patterns in pre-menstrual dysphoric disorder.

BACKGROUND: Pre-menstrual dysphoric disorder (PMDD) is commonly studied in white women; consequently, it is unclear whether the prevalence of PMDD varies by race. Although a substantial proportion of black women report symptoms of PMDD, the Biocultural Model of Women's Health and research on other psychiatric disorders suggest that black women may be less likely than white women to experience PMDD in their lifetimes. METHOD: Multivariate multinomial logistic regression modeling was used with a sample of 2590 English-speaking, pre-menopausal American women (aged 18-40 years) who participated in the Collaborative Psychiatric Epidemiology Surveys in 2001-2003. The sample consisted of 1672 black women and 918 white women. The measure of PMDD yields a provisional diagnosis of PMDD consistent with DSM-IV criteria. RESULTS: Black women were significantly less likely than white women to experience PMDD [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.25-0.79] and pre-menstrual symptoms (OR 0.64, 95% CI 0.47-0.88) in their lifetimes, independently of marital status, employment status, educational attainment, smoking status, body mass index, history of oral contraceptive use, current age, income, history of past-month mood disorder, and a measure of social desirability. The prevalence of PMDD was 2.9% among black women and 4.4% among white women. CONCLUSIONS: This study showed for the first time that black women were less likely than white women to experience PMDD and pre-menstrual symptoms, independently of relevant biological, social-contextual and psychological risk factors. This suggests that PMDD may be an exception to the usual direction of racial disparities in health. Further research is needed to determine the mechanisms that explain this health advantage.

Optimizing patient outcomes in laparoscopic surgery.

There is increasing recognition that the entire peri-operative care delivered plays a vital role in determining patient's outcome. Optimisation of this care helps to prevent complications beyond immediate morbidity and mortality. Of the 20 factors described in Enhanced Recovery Programmes, some have a greater impact than others, with analgesia and fluid therapy being two of the main factors. 1 Analgesia - The main analgesic regimes used so far for laparoscopic colorectal surgery have been continuous thoracic epidural and patient controlled analgesia. There is a growing body of opinion that epidural analgesia may not be required for laparoscopic surgery. 2 Individualised goal directed therapy - It is now recognized that measuring flow rather than pressure within the cardiovascular system is more important. Fluid therapy impacts on the outcome by minimizing fluid shifts, optimizing stroke volume and restricting the salt load given whilst maintaining normovolaemia. Analgesia and fluid therapy, together with the remaining enhanced recovery criteria have led to the development of the trimodal approach.

South African guidelines on the determination of death.

Death is a medical occurrence that has social, legal, religious and cultural consequences requiring common clinical standards for its diagnosis and legal regulation. This document compiled by the Critical Care Society of Southern Africa outlines the core standards for determination of death in the hospital context. It aligns with the latest evidence-based research and international guidelines and is applicable to the South African context and legal system. The aim is to provide clear medical standards for healthcare providers to follow in the determination of death, thereby promoting safe practices and high-quality care through the use of uniform standards. Adherence to such guidelines will provide assurance to medical staff, patients, their families and the South African public that the determination of death is always undertaken with diligence, integrity, respect and compassion, and is in accordance with accepted medical standards and latest scientific evidence. The consensus guidelines were compiled using the AGREE II checklist with an 18-member expert panel participating in a three-round modified Delphi process. Checklists and advice sheets were created to assist with application of these guidelines in the clinical environment (https://criticalcare.org.za/resource/death-determination-checklists/). Key points • Brain death and circulatory death are the accepted terms for defining death in the hospital context. • Death determination is a clinical diagnosis which can be made with complete certainty provided that all preconditions are met. • The determination of death in children is held to the same standard as in adults but cannot be diagnosed in children <36 weeks' corrected gestation. • Brain-death testing while on extra-corporeal membrane oxygenation is outlined. • Recommendations are given on handling family requests for accommodation and on consideration of the potential for organ donation. • The use of a checklist combined with a rigorous testing process, comprehensive documentation and adequate counselling of the family are core tenets of death determination. This is a standard of practice to which all clinicians should adhere in end-of-life care.