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Purpose: Parental exposures prior to conception might influence asthma and allergy risk in offspring. As occupational exposures are established risk factors for asthma and allergies, we investigated if parental occupational exposures prior to conception cause wheeze and eczema in offspring during the first year of life., Methods: We analysed data of 436 families from an offspring cohort based on a follow-up study of German participants of the International Study of Asthma and Allergies in Childhood (ISAAC). Offspring cohort data was collected between 2009 and 2019. Occupational exposures were based on participants' work histories and measured by a Job-Exposure-Matrix. We used Bayesian logistic regression models for analysis. Inference and confounder selection were based on directed acyclic graphs., Results: In mothers, for both allergic and irritative occupational exposures prior to conception suggestive effects on offspring eczema during the first year of life were found (allergens: odds ratio (OR) 1.22, 95% compatibility interval (CI) 0.92-1.57; irritants: OR 1.36, 95% CI 0.99-1.77), while no relation with wheeze was suggested., Conclusions: Our results suggest that reduction of asthma-related occupational exposures might not only reduce the burden of disease for occupationally induced or aggravated asthma and allergies in employees but also in their children., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To assess the dimensional establishment of a bony envelope after alveolar ridge preservation (ARP) with deproteinized bovine bone mineral (DBBM) in order to estimate the surgical feasibility of standard diameter implants placement without any additional augmentation methods., Methods: PubMed, Embase and CENTRAL databases were searched for suitable titles and abstracts using PICO elements. Inclusion criteria were as follows: randomized controlled trials (RCTs) comprising at least ten systemically healthy patients; test groups comprised placement of (collagenated) DBBM w/o membrane and control groups of no grafting, respectively. Selected abstracts were checked regarding their suitability, followed by full-text screening and subsequent statistical data analysis. Probabilities and number needed to treat (NNT) for implant placement without any further need of bone graft were calculated., Results: The initial database search identified 2583 studies. Finally, nine studies with a total of 177 implants placed after ARP with DBBM and 130 implants after SH were included for the quantitative and qualitative evaluation. A mean difference of 1.13 mm in ridge width in favour of ARP with DBBM could be calculated throughout all included studies (95% CI 0.28-1.98, t2 = 1-1063, I2 = 68.0%, p < 0.01). Probabilities for implant placement with 2 mm surrounding bone requiring theoretically no further bone augmentation ranged from 6 to 19% depending on implant diameter (3.25: 19%, RD = 0.19, C = 0.06-0.32, p < 0.01/4.0: 14%, RD = 0.14, C = 0.05-0.23, p < 0.01/5.0: 6%, RD = 0.06, C = 0.00-0.12, p = 0.06)., Conclusion: ARP employing DBBM reduces ridge shrinkage on average by 1.13 mm and improves the possibility to place standard diameter implants with up to 2 mm circumferential bone housing; however, no ARP would have been necessary or additional augmentative bone interventions are still required in 4 out of 5 cases., (© 2022. The Author(s).)

Aim: To evaluate the clinical non-inferiority of a 3-day protocol of systemic antibiotics adjunctive to subgingival instrumentation (SI) compared with a 7-day-protocol in patients with Stage III/IV Grade C periodontitis., Materials and Methods: Fifty systemically healthy patients (32.7 ± 4.3 years) with aggressive periodontitis (AgP; Stage III/IV Grade C periodontitis) were treated by SI and adjunctive amoxicillin and metronidazole and were randomly assigned to Group A: (n = 25) 500 mg antibiotics (AB) 3 times a day for 3 days, followed by placebo 3 times a day for 4 days, or Group B: (n = 25) 500 mg AB 3 times a day for 7 days. Clinical, microbial, and immunological parameters were assessed at baseline, 3 months, and 6 months, and patient-related outcomes were assessed after 2 weeks. The primary outcome variable was the number of residual sites with pocket depth (PD) ≥6 mm at 6 months., Results: For the primary outcome variable (the number of residual sites with PD ≥6 mm at 6 months), the null hypothesis was rejected and non-inferiority of the 3-day AB protocol compared with the 7-day AB protocol was demonstrated (the upper limits of the 95% confidence interval for intention to treat analysis: [-2.572; 1.050] and per protocol analysis: [-2.523; 1.318] were lower than the assumed margin of Δ = 3.1). Comparable clinical improvements were obtained for all parameters with both antibiotic protocols (p &gt; .05). All investigated periodontopathogens and pro-inflammatory host-derived markers were statistically significantly reduced without differences between the treatments (p &gt; .05)., Conclusions: These findings indicate that in patients with AgP (Stage III/IV Grade C periodontitis), a 3-day systemic administration of amoxicillin and metronidazole adjunctive to SI may lead to non-inferior clinical outcomes after 6-months with fewer adverse events compared with a 7-day-protocol., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Numerous scoring tools have been developed for assessing the probability of SARS-COV-2 test positivity, though few being suitable or adapted for outpatient triage of health care workers., Methods: We retrospectively analysed 3069 patient records of health care workers admitted to the COVID-19 Testing Unit of the Ludwig-Maximilians-Universität of Munich between January 27 and September 30, 2020, for real-time polymerase chain reaction analysis of naso- or oropharyngeal swabs. Variables for a multivariable logistic regression model were collected from self-completed case report forms and selected through stepwise backward selection. Internal validation was conducted by bootstrapping. We then created a weighted point-scoring system from logistic regression coefficients., Results: 4076 (97.12%) negative and 121 (2.88%) positive test results were analysed. The majority were young (mean age: 38.0), female (69.8%) and asymptomatic (67.8%). Characteristics that correlated with PCR-positivity included close-contact professions (physicians, nurses, physiotherapists), flu-like symptoms (e.g., fever, rhinorrhoea, headache), abdominal symptoms (nausea/emesis, abdominal pain, diarrhoea), less days since symptom onset, and contact to a SARS-COV-2 positive index-case. Variables selected for the final model included symptoms (fever, cough, abdominal pain, anosmia/ageusia) and exposures (to SARS-COV-positive individuals and, specifically, to positive patients). Internal validation by bootstrapping yielded a corrected Area Under the Receiver Operating Characteristics Curve of 76.43%. We present sensitivity and specificity at different prediction cut-off points. In a subgroup with further workup, asthma seems to have a protective effect with regard to testing result positivity and measured temperature was found to be less predictive than anamnestic fever., Conclusions: We consider low threshold testing for health care workers a valuable strategy for infection control and are able to provide an easily applicable triage score for the assessment of the probability of infection in health care workers in case of resource scarcity., (© 2022. The Author(s).)

A model-based clustering method for compositional data is explored in this article. Most methods for compositional data analysis require some kind of transformation. The proposed method builds a mixture model using Dirichlet distribution which works with the unit sum constraint. The mixture model uses a hard EM algorithm with some modification to overcome the problem of fast convergence with empty clusters. This work includes a rigorous simulation study to evaluate the performance of the proposed method over varied dimensions, number of clusters, and overlap. The performance of the model is also compared with other popular clustering algorithms often used for compositional data analysis (e.g. KMeans, Gaussian mixture model (GMM) Gaussian Mixture Model with Hard EM (Hard GMM), partition around medoids (PAM), Clustering Large Applications based on Randomized Search (CLARANS), Density-Based Spatial Clustering of Applications with Noise (DBSCAN) etc.) for simulated data as well as two real data problems coming from the business and marketing domain and physical science domain, respectively. The study has shown promising results exploiting different distributional patterns of compositional data., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Titanium bases are used frequently in daily practice for bonding to CAD/CAM abutments or crowns. Due to intimate contact between the adhesive gap of the titanium-base abutment and the peri-implant bone, the physical and chemical characteristics of the bonding material, or the gap itself, may affect peri-implant inflammatory reactions. The present study therefore aimed to examine the long-term effects of individualised abutments bonded to titanium bases on peri-implant health., Materials and Methods: A total of 24 patients, each with one test and one control abutment, participated in the present prospective, single-blind, randomised controlled clinical trial. The test abutments were CAD/CAM titanium abutments bonded to titanium bases. As the control abutments were individualised, one-piece CAD/CAM titanium abutments were used. Clinical and radiographic parameters were assessed at abutment insertion and then on a yearly basis over the following 5 years., Results: No significant differences in marginal bone level were observed between the titanium-base and one-piece abutments at any of the follow-up time points; however, when intragroup marginal bone levels were compared to the baseline values, significant differences were found at several follow-up time points. Intergroup differences were only found to be significant for pocket depth at the 4- (P = 0.006) and 5-year follow-ups (P = 0.024), favouring titanium-base abutments., Conclusions: Within the limitations of the present study, it appears that the peri-implant tissues of this specific patient cohort responded to titanium-base abutments in a rather similar manner to one-piece abutments over a 5-year period; however, no definitive conclusions can be drawn due to the low power of the present study.

To assess the course of the COVID-19 pandemic and the impact of non-pharmaceutical interventions, the number of reported positive test results is frequently used as an estimate of the true number of population-wide infections. We conducted a retrospective observational analysis of patient data of the Corona Testing Unit (CTU) in Munich, Bavaria, Germany between January 27th, and September 30th, 2020. We analyzed the course of daily patient numbers over time by fitting a negative binomial model with multiple breakpoints. Additionally, we investigated possible influencing factors on patient numbers and characteristics by literature review of policy papers and key informant interviews with individuals involved in the set-up of the CTU. The 3,963 patients included were mostly young (median age: 34, interquartile range: 27-48), female (66.2%), and working in the healthcare sector (77%). For these, 5,314 real-time RT-PCR tests were conducted with 157 (2.94%) positive results. The overall curve of daily tests and positive results fits the re-ported state-wide incidence in large parts but shows multiple breakpoints with considerable trend changes. These can be most fittingly attributed to testing capacities and -strategies and individual risk behavior, rather than public health measures. With the large impact on patient numbers and pre-test probabilities of various strategic and operational factors, we consider the derived re-ported incidence as a poor measurement to base policy decisions on. Testing units should be prepared to encounter these fluctuations with a quickly adaptable structure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hohl, Heumann, Rothe, Hoelscher, Janke and Froeschl.)

Objectives: To evaluate the relationship between gingival phenotype and tooth location based on selected index teeth ("Ramfjord") and assess possible differences between women and men., Material and Methods: Thirty-six women and 20 men voluntarily participated in this investigation with an average age of 23 years (min: 19; max: 37). Gingival phenotypes (GP) were assessed by transparency of a periodontal probe through the buccal gingival margin., Results: A comparable and similar GP on all index teeth was only found in seven out of the 56 subjects, that is, thin or thick only: Five participants (three male/two female) showed a uniform and constantly thick and two females a constantly thin GP. While the majority of molars (94.6%; p = 0.006) showed a thick GP, premolars (61.6%; p = 0.09) as well as incisors (70.5%; p = 0.046) were predominantly categorized as thin. In addition, significantly thicker GP was in general observed for maxillary teeth (p = 0.001) but without differences between genders (p = 0.722)., Conclusion: No constant GP can be expected within one dentition. The use of the "Ramfjord teeth" may serve as a quick overview and reliable method to screen GP distribution., (© 2021 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Precise measurements of periodontal parameters (such as pocket depths: PPD, gingival margins: GM) are important for diagnosis of periodontal disease and its treatment. Most examiners use manual millimeter-scaled probes, dependent on adequate pressure and correct readouts. Electronic probes aim to objectify and facilitate the diagnostic process. This randomized controlled trial compared measurements of a standard manual (MP) with those of an electronic pressure-sensitive periodontal probe (EP) and its influence on patients' acceptance and practicability. In 20 patients (2436 measuring points) PPD and GM were measured either with MP or EP by professionals with different levels of experience: dentist (10 patients), 7th and 10th semester dental students (5 patients each). Time needed was measured in minutes and patients' subjective pain was evaluated by visual analogue scale. Differences were analyzed using the generalized estimating equations approach (GEE) and paired Wilcoxon tests. Mean PPD varied with ΔPPD 0.38 mm between both probes, which was significant ( p < 0.001), but GM did not (ΔREC 0.07 mm, p = 0.197). There was a statistically significant correlation of both probes (Spearman's rho correlation coefficient GM: 0.674, PPD: 0.685). Differences can be considered robust (no deviation in either direction). The comparison of time needed and pain sensitivity did not result in statistically significant differences ( p > 0.05).

Objectives: This study aimed to investigate the additional clinical benefit of tricalcium phosphate (TCP) (-containing) biomaterials compared to open flap debridement (OFD) in periodontal infra-bony defects., Data: A literature search was conducted in Pubmed, Embase and Cochrane library for entries published up to 14th July 2021. All randomized controlled trials (RCTs) that compared a TCP (-containing) material with OFD and studies that assessed a beta-TCP group alone, with vertical defect sites with PPD of ≥ 6 mm and/or presence of infra-bony defects of ≥ 3 mm and a minimum follow-up of 6 months were included. Risk of bias was assessed with the Oxford scale. The random-effects (RE) model was synthesized as differences between weighted average (MD) for probing pocket depth (PPD) and clinical attachment level (CAL) between TCP and OFD groups. An RE analysis was also performed for the beta-TCP group alone., Study Selection: Data from 16 RCTs were included in the analysis. Six studies that represented 151 patients and sites were selected for meta-analysis. The overall MD with 95% CI at 6 months was calculated to be -0.47 [-0.83, -0.12; P = 0.0087] and -1.06 [-1.67, -0.46; P = 0.0006] for PPD and CAL, respectively. Whereas MD at 12 months for PPD and CAL was -0.89 [-1.54, -0.23; P = 0.0078] and -1.25 [-1.85, -0.66; P<0.0001], respectively. All results were in favor of TCP (-containing) group over OFD., Conclusions: The results of the study suggest that the use of a TCP (-containing) material may have the potential for additional clinical improvement in PPD and CAL compared with OFD in infra-bony defects, given the limitations of the included evidence., Clinical Significance: The use of TCP as a bone graft substitute is becoming increasingly common. Therefore, it would be advantageous if an adjunctive benefit in the regeneration of infra-bony defects could be demonstrated to facilitate material selection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This single-center, clinically controlled, double-blinded, randomised, crossover study aimed to evaluate and compare the antibacterial effect, substantivity and patients' acceptance of three toothpaste slurries after a single application on established biofilms observed for 24 h., Materials and Methods: Twenty-four participants started a test cycle after refraining from oral hygiene for 48 h, with a baseline plaque sample measuring biofilm vitality (in %; VF0) using vital fluorescence (VF). They were instructed to rinse for 1 min with either an amine fluoride, stannous chloride (ASC), an herbal (SBC) or a sodium fluoride (SFL) toothpaste prepared as slurries. Every two hours up to 12 and after 24 h, plaque samples were harvested (VF2-VF24%). Plaque-covered areas (PA in %) were evaluated after 24 h using digital photographs. Patients' acceptance was determined by visual analogue scale (VAS) questionnaire., Results: All participants (16 women, 8 men; 27.5 ± 7.9 years) completed all cycles. Two hours after application (VF2), all toothpastes showed a statistically significant reduction in bacterial vitality (p < 0.05), maintained up to 12 h. ASC revealed statistically significantly lower vitality values compared to SBC at VF2, VF4, VF8, VF12 and VF24, and at VF4, VF12 and VF24 compared to SFL (p < 0.05), while SBC and SFL did not differ statistically significantly at any time point. The preferred toothpastes were SFL (18/24 participants) and ASC (15/24 participants)., Conclusions: All toothpastes showed statistically significant anti-plaque effects on established plaque biofilm and a substantivity up to 24 h compared to their baseline, while ASC still presented a statistically significant effect after 12 and 24 h compared to SBC and SFL.

The need to monitor changes in parasite clearance following treatment with artemisinin-based combination therapies (ACTs) is important in the containment of drug resistance. This study aimed to model Plasmodium falciparum response to ACTs among children in two different transmission settings (Mutengene and Garoua) in Cameroon. Using the step function, a discrete-time survival model was fitted with all the covariates included that might play a role in parasite clearance. The probability of clearing parasites within 24 h following treatment was 21.6% and 70.3% for younger children aged 6 to 59 months and 29.3% and 59.8% for older children aged 60 to 120 months in Mutengene and Garoua, respectively. After two days of treatment, the conditional probability of clearing parasites given that they were not cleared on day 1 was 76.7% and 96.6% for children aged 6-59 months and 83.1% and 93.5% for children aged 60-120 months in Mutengene and Garoua, respectively. The model demonstrated that the ecological setting, age group and pretreatment serum levels of creatinine and alanine aminotransferase were the main factors that significantly influenced parasite clearance in vivo after administration of ACTs ( p < 0.05). The findings highlight the need for further investigations on host differential response to ACTs in current practice.

Background: The World Health Organization (WHO) declared the West Africa Ebola epidemic as a Public Health Emergency of International Concern in August 2014. During the outbreak period, there were calls for the affected countries to construct Ebola treatment centres and reliable diagnostic laboratories closer to areas of transmission in order to improve the quality care of Ebola Virus Disease (EVD) patients. Delay in seeking treatment has been reported to have led to poor treatment outcome of EVD patients. Sierra Leone recorded more than 8000 probable and confirmed cases and more than 4000 EVD -related deaths nation-wide., Methods: In this retrospective study, we investigated the effects of treatment delay, length of symptomatic period, EVD patients' sex, age, occupation, region of residence, and clinical characteristics on the treatment outcome of 205 laboratory-confirmed EVD patients who were admitted at the Kenema Government Hospital Ebola Treatment Center (KGHETC) from 13/09/2014-26/11/2014; i.e. during the peak of 2013-2016 EVD outbreak in Sierra Leone. Specifically also, we determined the factors that were associated with the length of stay for EVD treatment for patients who were discharged alive., Results: Majority (66.3%, n = 205/309) of the 309 suspected EVD patients with medical records at the KGHETC triage during the period under review were tested positive for EVD using reverse-transcriptase-polymerase chain reaction (RT-PCR) and had a definitive treatment outcome. Few (33.7%, n = 104/309) suspected EVD patients were not included in our analysis and were classified thus: 29.1% (n = 90/309) suspect EVD cases with negative RT-PCR results, 4.5% (n = 14/309) suspect cases with non-available RT-PCR result. Of the 205 patients, 99 (48.3%) had a fatal outcome. For EVD patients that survived, we recorded a significant association (- 0.06, 95% Confidence Interval (CI) = - 0.14 - - 0.02, p = 0.004) between the Length of Stay (LOS) and for each kilometer travelled to seek treatment at the KGHETC. However, the association between EVD patients that were low skilled workers (- 5.91, 95% CI = - 24.60 - 12.79, p = 0.73), EVD patients who were children and pupils in junior school (- 0.86, 95% CI = - 12.86 - 11.14, p = 0.73), health seeking delay for EVD patients who resided in Kenema District where the KGHETC was located (- 0.49, 95% CI = - 0.12 - 1.09, p = 0.24), sex (- 1.77, 95% CI = - 8.75 - 5.21, p = 0.50), age (0.21, 95% CI = - 0.36 - 0.77, p = 0.57), referral status (1.21, 95% CI = - 17.67 - 20.09, p = 0.89) and the LOS in surviving patients were not statistically significant., Conclusion: The high LOS for either treatment outcome for EVD patients that resided in the district in which the EVD treatment facility was located compared to those patients from other districts implies that health authorities should consider intensive health education with high priority given to seeking early EVD treatment, and the construction of strategic ETCs as important components in their response strategy., (© 2021. The Author(s).)

Multiple Imputation (MI) is always challenging in high dimensional settings. The imputation model with some selected number of predictors can be incompatible with the analysis model leading to inconsistent and biased estimates. Although compatibility in such cases may not be achieved, but one can obtain consistent and unbiased estimates using a semi-compatible imputation model. We propose to relax the lasso penalty for selecting a large set of variables (at most n). The substantive model that also uses some formal variable selection procedure in high-dimensional structures is then expected to be nested in this imputation model. The resulting imputation model will be semi-compatible with high probability. The likelihood estimates can be unstable and can face the convergence issues as the number of variables becomes nearly as large as the sample size. To address these issues, we further propose to use a ridge penalty for obtaining the posterior distribution of the parameters based on the observed data. The proposed technique is compared with the standard MI software and MI techniques available for high-dimensional data in simulation studies and a real life dataset. Our results exhibit the superiority of the proposed approach to the existing MI approaches while addressing the compatibility issue., Competing Interests: The authors have declared that no competing interests exist.

Probiotics' ability to integrate into dental biofilms is not yet clarified. The aim of this trial was to detect probiotic bacteria from probiotic products in dental biofilm and saliva during and after intake. In this parallel, randomized clinical trial, 39 subjects wore customized appliances to build up intra-oral biofilms (72-h periods). The trial was divided into screening (S) to determine baseline biofilm flora, intervention (I), and wash out (WO). During I (28 days), subjects consumed a product containing (a) Enterococcus faecalis (b) Lactobacillus , or (c) casei , or (c) Lactobacillus rhamnosus GG. Probiotic bacteria and Streptococci spp. were detected in the biofilms and saliva of the 35 subjects that were included in the analysis. During I and WO, the ratio of probiotics in the biofilm was very low compared to total bacterial load, while saliva had slightly but not significantly higher values. No significant changes of probiotic bacteria ( p > 0.05) were found at any visit during I or WO. The proportion of streptococci was significantly reduced ( p < 0.05) during I and even lower in WO, compared to S. Probiotic bacteria could neither integrate nor persist in dental biofilm and saliva but did influence the growth of streptococci in biofilm and saliva.

Purpose: Sierra Leone recorded the highest incidence rate for the 2013-2016 West African Ebola outbreak. In this investigation, we used the medical records of Ebola patients with different sociodemographic and clinical features to determine the factors that are associated with Ebola treatment outcome during the 2013-2016 West African Ebola outbreak in Sierra Leone and constructed a predictive in-facility mortality score., Methods: We used the anonymized medical records of 1077 laboratory-confirmed pediatric and adult patients with EVD who received treatment at the 34 Military Hospital and the Police Training School Ebola Treatment Centers in Sierra Leone between the period of June 2014 and April 2015. We later determined the in-facility case fatality rates for Ebola, the odds of dying during Ebola treatment, and later constructed a predictive in-facility mortality score for these patients based on their clinical and sociodemographic characteristics., Results: We constructed a model that partitioned the study population into three mortality risk groups of equal patient numbers, based on risk scoring: low (score ≤ -5), medium (score -4 to 1), and high-risk group (score ≥ 2). The CFR of patients with EVD belonging to the low- (≤-5), medium (-4 to 1), and high- (≥2) risk groups were 0.56%, 9.75%, and 67.41%, respectively., Conclusions: We succeeded in designing an in-facility mortality risk score that reflects EVD clinical severity and can assist in the clinical prioritization of patients with EVD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Exploratory factor analysis is a statistical method commonly used in psychological research to investigate latent variables and to develop questionnaires. Although such self-report questionnaires are prone to missing values, there is not much literature on this topic with regard to exploratory factor analysis-and especially the process of factor retention. Determining the correct number of factors is crucial for the analysis, yet little is known about how to deal with missingness in this process. Therefore, in a simulation study, six missing data methods (an expectation-maximization algorithm, predictive mean matching, Bayesian regression, random forest imputation, complete case analysis, and pairwise complete observations) were compared with respect to the accuracy of the parallel analysis chosen as retention criterion. Data were simulated for correlated and uncorrelated factor structures with two, four, or six factors; 12, 24, or 48 variables; 250, 500, or 1,000 observations and three different missing data mechanisms. Two different procedures combining multiply imputed data sets were tested. The results showed that no missing data method was always superior, yet random forest imputation performed best for the majority of conditions-in particular when parallel analysis was applied to the averaged correlation matrix rather than to each imputed data set separately. Complete case analysis and pairwise complete observations were often inferior to multiple imputation., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Background: The 2013-2016 West Africa Ebola Virus Disease (EVD) outbreak recorded the highest incidence and mortality since the discovery of the virus in Zaire in 1976; with more than 28,000 probable and confirmed EVD cases and 11,000 deaths. Studies relating to previous outbreaks usually involved small sample sizes. In this study we are set to identify those sociodemographic and clinical features that predict in-facility mortality among EVD patients using a large sample size., Methods: We analysed the anonymized medical records of 938 laboratory-confirmed EVD patients 15 years old and above who received treatment at The 34 Military Hospital and The Police Training School EVD Treatment Centers in Sierra Leone in the period June 2014 to April 2015. We used both univariable and multivariable logistic regression to determine the predictors for in-facility mortality of these patients based on their sociodemographic and clinical characteristics., Results: The median age of the EVD cases was 33 years (interquartile range = 25 to 40 years). The majority of the EVD cases were male (59.0%) and had secondary level education (79.3%). We reported a low overall in-facility case fatality rate of 26.4%. The associations between case fatality rates and EVD patients who reported fever, abdominal pain, cough, diarrhoea, vomiting, fatigue, haemorrhage, dysphagia, conjunctival injection, dyspnea, and skin rash at the time of admission were all statistically significant (p <  0.05). Our preferred model with the age group 65 years and above alongside the following clinical symptoms; diarrhoea, vomiting, fatigue, dysphagia, conjunctival injection, dyspnea and cough produced a receiver operating characteristic (ROC) curve with an AUC (area under the curve) value of 0.93., Conclusions: We constructed a simple model that can be optimally used alongside other rapid EVD diagnostic tools to identify EVD in-facility treatment mortality predictors based on the sociodemographic characteristics and clinical symptoms of adult EVD patients. We also reported low EVD cases among patients with secondary and tertiary education. These subpopulations of our patients who are generally informed about the signs and symptoms of EVD, alongside our treatment regimen may have been responsible for our comparatively lower case fatality rate.

Objectives: This single-centre, controlled, randomized, double-blinded clinical study in parallel groups was performed to assess the efficacy of an experimental toothpaste on plaque and gingivitis., Methods: In adult subjects with gingivitis, amine fluoride/stannous chloride toothpaste (test) and monofluorophosphate toothpaste (control) were applied twice daily by regular toothbrushing at home. Evaluations of plaque index (PI), gingival index (GI), modified sulcus bleeding index (mSBI) and safety took place at baseline and after 3 and 12 weeks of study product use. After study completion, all subjects received a dental prophylaxis. A descriptive statistical analysis included means and standard deviations. Unpaired t tests compared index reductions between groups at a significance level of 0.05., Results: Intention-to-treat analysis included 240 out of 241 subjects. Baseline mean PI was reduced by 0.87 ± 0.35 in the test group and by 0.65 ± 0.41 in the control group. Within-group differences and between-group differences in index reduction were statistically significant (P < 0.001). Mean GI and mSBI were reduced significantly over time (P < 0.001) with no clinically meaningful differences between groups., Conclusions: Both toothpastes reduced plaque and gingivitis statistically significant and clinically meaningful over 12 weeks. Compared to the control toothpaste, application of the amine fluoride/stannous chloride toothpaste led to a clinically meaningful and more pronounced plaque reduction., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Missing data is a common issue that can cause problems in estimation and inference in biomedical, epidemiological and social research. Multiple imputation is an increasingly popular approach for handling missing data. In case of a large number of covariates with missing data, existing multiple imputation software packages may not work properly and often produce errors. We propose a multiple imputation algorithm called mispr based on sequential penalized regression models. Each variable with missing values is assumed to have a different distributional form and is imputed with its own imputation model using the ridge penalty. In the case of a large number of predictors with respect to the sample size, the use of a quadratic penalty guarantees unique estimates for the parameters and leads to better predictions than the usual Maximum Likelihood Estimation (MLE), with a good compromise between bias and variance. As a result, the proposed algorithm performs well and provides imputed values that are better even for a large number of covariates with small samples. The results are compared with the existing software packages mice, VIM and Amelia in simulation studies. The missing at random mechanism was the main assumption in the simulation study. The imputation performance of the proposed algorithm is evaluated with mean squared imputation error and mean absolute imputation error. The mean squared error ( β ^ ), parameter estimates with their standard errors and confidence intervals are also computed to compare the performance in the regression context. The proposed algorithm is observed to be a good competitor to the existing algorithms, with smaller mean squared imputation error, mean absolute imputation error and mean squared error. The algorithm's performance becomes considerably better than that of the existing algorithms with increasing number of covariates, especially when the number of predictors is close to or even greater than the sample size. Two real-life datasets are also used to examine the performance of the proposed algorithm using simulations.

Objectives: To assess the efficacy of 8% arginine containing prophylaxis products over 24 weeks in subjects with dentin hypersensitivity (DH)., Methods: 297 patients with established DH (Schiff score 2, 3) in three European study centers were randomly assigned to either 8% arginine and calcium carbonate in-office prophylaxis paste and the respective toothpaste (test group) or fluoride-free prophylaxis paste and sodium monoflourophosphate toothpaste as a negative control group. Air blast (Schiff Score) and tactile (Visual Analog Scale) sensitivity scores were assessed at baseline (BL&#95;0), after single application of the prophylaxis paste (BL&#95;1) and after 4, 8, and 24 weeks of continuous at-home use of the toothpaste., Results: 273 subjects completed the study. Test and control group presented statistically significant percentage reductions (t-test, p < 0.05) in Schiff Score at BL&#95;1 and at 24 weeks relative to BL&#95;0 (difference in %; test group: -23.6, -44.9, control group: -8.8, -32.7). The pooled Schiff Score for the two evaluated teeth yielded a significantly greater alleviation of DH in the test group than in the control group at all evaluation appointments (Ancova, p < 0.05; difference in %: 15.3, 7.4, 10.6, 17.2)., Conclusions: A significant relief of DH was demonstrated after application of the 8% arginine prophylaxis products over 24 weeks compared to a negative control., Clinical Significance: Whilst DH is influencing patients' eating, drinking and tooth brushing habits as well as social life interactions it is important that clinicians are able to offer evidence based immediate and long-lasting treatment methods in order to manage their patients' discomfort., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Diabetes and periodontitis are considered associated chronic diseases, and hyperinsulinemia in prediabetes has been shown to be present in normoglycemic animals with periodontitis. As periodontal bacterial species are significant sources of endotoxemia and may directly stimulate insulin secretion, we hypothesized that increased bacterial virulence may exert an adverse effect on rat pancreatic β-cell function via PI3K/AKT signaling. INS-1 cells and isolated pancreatic islets were cultured separately with the following supernatants: Streptococcus anginosus, Streptococcus mutans, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis (P.g), and Treponema denticola (T.d). Supernatants were purified from single bacterial cultures and prepared at different dilutions (100 pg/ml, 50 ng/ml, 200 ng/ml, and 500 ng/ml) to challenge INS-1 and islets. Gene expression (IL-1β, TNFα, IL-6, TLR2, TLR4, Ins1, and Ins2) and insulin secretion were measured. The results showed upregulation of gene expression up to 5.5-fold, not only as a result of the different dilutions used, but also due to bacterial virulence (p < 0.05). P.g and T.d supernatants demonstrated an increase in insulin secretion to fivefold at hypo- and hyperglycemia, yet stimulation from hypo- to hyperglycemia stays in the same ratio. Activation of TLR4/PI3K/AKT signaling by supernatants in INS-1 cells resulted in increased IL-1β, TNFα, IL-6 gene expression levels, and AKT phosphorylation, which were abolished by TLR4 and PI3K/AKT signaling inhibitor. We demonstrated that bacterial supernatants derived from gram-negative species increasingly stimulate insulin secretion in β-cells and TLR4 may promote inflammation by activating the PI3K/AKT signaling pathway to induce pro-inflammatory molecules. Bacterial species, depending on their virulence, appear to play a role in the relationship between periodontitis and prediabetes by promoting insulin resistance and β-cell compensatory response.

Background: The West Africa Ebola Virus Disease (EVD) outbreak in 2014-2016 was declared by the World Health Organization (WHO) a public health emergency of international concern. Most of the previous studies done in Sierra Leone relating to the clinical and epidemiological features of EVD during the 2014-2016 West African outbreak focused on adult EVD patients. There have been conflicting reports about the effects of EVD on children during previous outbreaks., Methods: This is an observational retrospective analysis of medical data of all laboratory confirmed paediatric EVD patients below 15 years of age who were admitted at the 34 Military Hospital Ebola Treatment Center (ETC) in Wilberforce, Sierra Leone between June 2014 to April 2015. We analyzed the sociodemographic and clinical characteristics of paediatric EVD cases contained in case report forms that were collected by Ebola surveillance officers and clinicians at the 34 Military Hospital ETC. Both univariate and multivariate logistic regression models were used to determine the sociodemographic and clinical characteristics of paediatric EVD patients that were associated with EVD facility-based mortality., Results: The majority of the paediatric EVD cases in this study were female (56.1%), pupils (51.1%), and 43.2% belonged to the age group between 10 years and below 15 years. The median age of the paediatric EVD cases was 9 years (interquartile range = 4 to 11 years). Adjusting for other covariates in the model, male paediatric EVD patient (AOR = 13.4, 95% CI = [2.07-156-18], p <  0.05), EVD patient with abdominal pain (AOR = 11.0, 95% CI = [1.30-161.81], p <  0.05), vomiting (AOR = 35.7, 95% CI = [3.43-833.73], p <  0.05), signs of conjunctivitis (AOR = 17.4, 95% CI = [1.53-342.21], p <  0.05) and difficulty in breathing (AOR = 23.3, 95% CI = [1.92-713.01], p <  0.05) at the time of admission had increased odds of dying during EVD treatment., Conclusions: We recommend the adoption of case definitions currently in vigour to cater for specific characteristics of paediatric patients. Subgroups that can be identified by applying the model developed in this study may require special attention and intensified care.

Background Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy, but it is unclear how best to deliver PrEP to key populations. Drawing upon a cross-sectional survey of transgender women (TW) in Detroit, USA, and experience of a PrEP clinic that serves this population, this manuscript describes the following: (1) the risk profile of Detroit TW; (2) the proportion of TW with at least one PrEP indication; and (3) perceptions of and experiences with PrEP among TW in Detroit., Methods: Between August 2017 and March 2018, 126 TW completed an online PrEP survey. Survey responses were summarised using descriptive statistics and multivariable relative risk regression., Results: Among participants who reported a negative or unknown HIV status (76% of all participants), 56% reported risk behaviour(s) consistent with PrEP indication guidelines, 17% reported currently taking PrEP and another 4% reported discontinued PrEP use. Among participants who met an indication for PrEP but were not currently taking PrEP, 64% indicated that they were not interested in taking PrEP. Approximately 60% of participants who were not currently taking PrEP reported that they would be more likely to take PrEP if it were provided at a clinic that also provided hormone replacement therapy., Conclusions: Although a substantial proportion of TW in our survey were on PrEP, interest in PrEP among high-risk TW who were not taking it was low. Specialised clinical infrastructure that is responsive to the specific needs of TW may be needed to expand PrEP to this oftentimes marginalised and high-risk population.

Previous studies have reported an increased risk for certain types of cancer in the HIV-infected population. The aim of this study was to assess the risk for cancer in people with AIDS (PWA) in comparison with the general population in São Paulo (Brazil), between 1997 and 2012. A population-based registry linkage study was carried out to assess the risk for cancer, using a standardized incidence ratio (SIR) approach. A total of 480 102 person-years, of which 337 941 (70.4%) person-years were men, were included in the analysis. Around 2074 cancer cases were diagnosed among PWA, of which 51.0% were non-AIDS-defining cancers (NADC). The risk for AIDS-defining cancers and NADC in the male population with AIDS was significantly higher than that in the general population (SIR=27.74 and 1.87, respectively), as it was in the female population with AIDS compared with the general population (SIR=8.71 and 1.44, respectively). Most virus-related NADC occurred at elevated rates among PWA: anal cancer (SIR=33.02 in men and 11.21 in women), liver (SIR=4.35 in men and 4.84 in women), vulva and vagina (SIR=6.78 in women) and Hodgkin lymphoma (SIR=5.84 in men and 2.71 in women). Lung (SIR=2.24 in men and 2.60 in women) and central nervous system (SIR=1.92 in men and 3.48 in women) cancers also occurred at increased rates. Cancer burden among PWA in São Paulo was similar to that described in high-income countries such as the USA and Italy following the introduction of the highly active antiretroviral therapy. As coinfection with oncogenic viruses disproportionally affects this population, virus-related cancers accounted for a great share of excessive cases.

Objectives: The objective of this study is to evaluate the effects of treatment modalities on titanium surface characteristics and surrounding tissues., Materials and Methods: Eighteen participants each had four titanium healing caps (HC) attached to four newly inserted implants. After healing, each HC was randomly assigned to either (1) titanium curettes (TC), (2) stainless steel ultrasonic tip (PS), (3) erythritol air-polishing powder (EP), or (4) only rubber cup polishing (CON). Probing depths (PD), bleeding on probing (BOP), matrix metalloproteinase 8 (MMP-8), and periopathogens were recorded before and 3 months following instrumentation. After final assessments, HCs were removed, cleaned, and subjected to (a) bacterial colonization (Streptococcus gordonii, 24 h; mixed culture, 24 h) and (b) gingival fibroblasts (5 days). HC surfaces were analyzed with a scanning electron microscope (SEM)., Results: No significant differences between the groups were evident before or after instrumentation for PD and BOP (except TC showed a significant decrease in PD; p = 0.049). MMP-8 levels and bacterial loads were always very low. MMP-8 decreased further after instrumentation, while bacteria levels showed no change. No significant differences (p > 0.05) were evident in bacterial colonization or fibroblast attachment. A comparison of the overall mean SEM surface roughness scores showed a significant difference between all groups (p < 0.0001) with the lowest roughness after EP., Conclusions: All treatments performed yielded comparable outcomes and may be implemented safely., Clinical Relevance: Clinicians may fear implant surface damage, but all instrumentation types are safe and non-damaging. They can be implemented as needed upon considering the presence of staining and soft and hard deposits.

Many modern estimators require bootstrapping to calculate confidence intervals because either no analytic standard error is available or the distribution of the parameter of interest is nonsymmetric. It remains however unclear how to obtain valid bootstrap inference when dealing with multiple imputation to address missing data. We present 4 methods that are intuitively appealing, easy to implement, and combine bootstrap estimation with multiple imputation. We show that 3 of the 4 approaches yield valid inference, but that the performance of the methods varies with respect to the number of imputed data sets and the extent of missingness. Simulation studies reveal the behavior of our approaches in finite samples. A topical analysis from HIV treatment research, which determines the optimal timing of antiretroviral treatment initiation in young children, demonstrates the practical implications of the 4 methods in a sophisticated and realistic setting. This analysis suffers from missing data and uses the g-formula for inference, a method for which no standard errors are available., (Copyright © 2018 John Wiley & Sons, Ltd.)

Cancer survival among people with AIDS (PWA) has been described in developed countries, but there is lack of data from developing countries. The aim of this study was to evaluate survival after cancer diagnosis in PWA and compare it with people without AIDS (non-PWA) in São Paulo, Brazil. A probabilistic record linkage was carried out between the databases of the Population-based Cancer Registry of São Paulo (PBCR-SP) and the AIDS registry of SP (SINAN) to identify PWA who developed cancer. For comparison, non-PWA were frequency matched from the PBCR-SP by cancer site/type, sex, age, and period. Hazard ratio (HR) stratified by matching variables was estimated using a Cox proportional hazards model. A total of 1,294 PWA (20 patients with two primary site tumors) were included in the site/type-specific analyses. AIDS-defining cancers (ADC) comprised 51.9% of cases assessed. The all-cancer 5-year overall survival in PWA was 49.4% versus 72.7% in non-PWA (HR = 2.64; 95%CI = 2.39-2.91). Survival was impaired in PWA for both ADC (HR = 2.93; 95%CI = 2.49-3.45) and non-ADC (HR = 2.51; 95%CI = 2.21-2.84), including bladder (HR = 8.11; 95% CI = 2.09-31.52), lung (HR = 2.93; 95%CI = 1.97-4.36) and anal cancer (HR = 2.53; 95%CI = 1.63-3.94). These disparities were seen mainly in the first year after cancer diagnosis. The overall survival was significantly lower in PWA in comparison with non-PWA in São Paulo, as seen in high-income countries. Efforts to enhance early diagnosis and ensure proper cancer treatment in PWA should be emphasized., (© 2017 UICC.)

Purpose: This double-blind, clinical, cross-over study evaluated the antibacterial effect of three toothpastes (ASF, HTP and STP) and a chlorhexidine mouthrinse (0.2%; CHX; positive control) after a single application on established biofilm over a period of 24 h (substantivity)., Materials and Methods: Twenty-four subjects refrained from all oral hygiene measures for a period of 72 h. After 48 h, a baseline biofilm sample was taken and vitality of the biofilm flora was examined (baseline, VF0). Then they rinsed for 1 min with one of the randomly allocated, freshly prepared toothpaste slurries (ASF, HTP, STP) or CHX. Further biofilm samples were taken every second hour up to 14 h as well as 24 h after rinsing, and biofilm vitality was assessed (VF2-24). After a wash-out period of 4 days, a new test cycle was started., Results: All subjects (18 female, 6 male) finished the four test cycles. At VF2, all products showed a statistically significant reduction in vitality compared to VF0 (p<0.05). CHX and ASF revealed the most pronounced effect (49% and 40% reduction), while the other toothpastes (HTP: 24%, STP: 11%) reached lower but still statistically significant effects. At each further time point CHX and ASF showed the lowest biofilm vitality. ASF demonstrated a significant antibacterial effect on dental biofilm over a 24-h period compared to baseline and superiority over both other toothpastes at time points VF2-VF14., Conclusion: ASF toothpaste showed a significant antibacterial action on biofilm and a high substantivity which was maintained up to 24 hours.

Objectives: To measure the effect of orthognathic surgery on Class II:1 profile silhouette esthetics and to identify pretreatment parameters and thresholds for consistent esthetic improvement., Methods: Pre- and posttreatment black profile silhouettes of 20 patients with Class II:1 malocclusion who had received combined orthodontic/orthognathic treatment were evaluated retrospectively by 20 European orthodontists and laypeople each using a visual analogue scale (VAS). A variety of pretreatment skeletal and facial angles were measured cephalometrically and on the silhouette profiles. Descriptive statistics and Pearson's correlation coefficients were calculated., Results: The population showed a mean VAS improvement of 12.6%. VAS changes were significantly and directly related to pretreatment ANB in all evaluator groups (r = 0.48-0.59), whereas the interrelation with the degree of pretreatment profile convexity angle was less clear and statistically significant for the orthodontic evaluators only (r = -0.34 to -0.51). The highest correlation coefficients in all evaluator groups were seen for the relationship with pretreatment VAS scores (r = -0.64 to -0.73)., Conclusion: The lower the pretreatment VAS score and the profile convexity angles or the larger the pretreatment ANB angles were, the more the VAS improved. Pretreatment thresholds for consistent improvements were as follows: VAS score < 20 mm, ANB > 8°, and profile angle ≤ 155°.

People living with AIDS are at increased risk of developing certain cancers. Since the introduction of the highly active antiretroviral therapy (HAART), the incidence of AIDS-defining cancers (ADCs) has decreased in high-income countries. The objective of this study was to analyse trends in ADCs and non-AIDS-defining cancers (NADCs) in HIV-positive people with a diagnosis of AIDS, in comparison to the general population, in São Paulo, Brazil. A probabilistic record linkage between the 'Population-based Cancer Registry of São Paulo' and the AIDS notification database (SINAN) was conducted. Cancer trends were assessed by annual per cent change (APC). In people with AIDS, 2074 cancers were diagnosed. Among men with AIDS, the most frequent cancer was Kaposi's sarcoma (469; 31.1%), followed by non-Hodgkin lymphoma (NHL; 304; 20.1%). A decline was seen for ADCs (APC = -14.1%). All NADCs have increased (APC = 7.4%/year) significantly since the mid-2000s driven by the significant upward trends of anal (APC = 24.6%/year) and lung cancers (APC = 15.9%/year). In contrast, in men from the general population, decreasing trends were observed for these cancers. For women with AIDS, the most frequent cancer was cervical (114; 20.2%), followed by NHL (96; 17.0%). Significant declining trends were seen for both ADCs (APC = -15.6%/year) and all NADCs (APC = -15.8%/year), a comparable pattern to that found for the general female population. Trends in cancers among people with AIDS in São Paulo showed similar patterns to those found in developed countries. Although ADCs have significantly decreased, probably due to the introduction of HAART, NADCs in men have shown an opposite upward trend.

Background  This retrospective study aims to measure the effect of the disease management program (DMP) for type 2 diabetes mellitus (T2DM) patients on HbA 1c value within Germany. Methods  This study is based on patient data from the Disease Analyzer panel (IMS Health). An adequate control group was created using 2:1 propensity score matching. After matching, the analysis included 14 759 patients. Of these, 5875 participated in a DMP while 8884 received standard care. The DMP effect was estimated on the basis of the matched data, using an unpaired t-test. In addition, subgroups were considered from the perspective of personalized medicine. Results  The reduction in HbA 1c values in the DMP group amounted to an average of 1.0 percentage point (baseline HbA 1c  = 8.1 vs. final HbA 1c  = 7.1), while the SC group was able to achieve an average reduction in HbA 1c values of 0.9 percentage point (baseline HbA 1c  = 8.1 vs. final HbA 1c  = 7.2). The DMP group thus achieved an average reduction in HbA 1c values that exceeded that of the SC group by only 0.1 percentage point (95 % CI: 0.04 - 0.16). Descriptively, it also became apparent that patients from the DMP group received a greater average number of annual prescriptions and had more HbA 1c measurements. The subgroup analysis identified groups of patients who benefit more from DMPs than others. Thus, young patients or patients who are being treated by diabetologists are able to benefit most from a DMP. Furthermore, the baseline HbA 1c value has an influence on the DMP effect. Conclusion  T2DM patients in the DMP exhibit a significantly higher reduction in HbA 1c value. However, it is questionable whether this effect is clinically relevant. Certain groups of patients benefit more from DMPs than others. Nevertheless, further studies are needed in order to better understand the impact of the DMP on HbA 1c value and the reasons for the subgroup effects. Such studies should be carried out using a randomized controlled design., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The present retrospective study examines the influence of disease management programs on nonfatal stroke in type 2 diabetes mellitus (T2DM) patients in Germany., Methods: The evaluation is based on retrospective patient data from the Disease Analyzer (IMS Health). The analysis included 169 414 T2DM patients aged 40 years and older with an initial prescription of antihyperglycemic therapy between January 2004 and December 2014. A total of 86 713 patients participated in a disease management program (DMP) for T2DM and 82 701 patients received standard care. The main outcome measure of this study was nonfatal stroke. Kaplan-Meier curves of DMP and SC patients were compared using log rank test. The Cox proportional hazards model was used to provide an adjusted estimate of the DMP effect., Results: It is apparent from the baseline characteristics that the general health of patients receiving standard care was poorer than that of patients participating in a DMP. The baseline HbA1c value was 7.6% in the DMP group and 7.8% in the SC group. Furthermore, the SC group had a higher proportion of preexisting conditions, such as coronary heart disease (CHD), peripheral arterial occlusive disease (pAOD), and renal insufficiency. The proportion of patients who received insulin in first year therapy was higher in the SC group. Time to event analysis showed that DMP was associated with a delayed occurrence of stroke, because stroke occurred an average of 350 days later in DMP patients than in patients receiving SC (DMP: 1.216 days, RV: 866 days). The Cox model with covariable adjustment confirmed the significant association of DMPs with nonfatal stroke in patients with type 2 diabetes mellitus (HR 0.71; 95% CI: 0.69-0.74)., Conclusion: The present study indicates that DMPs are positively associated with stroke. The possible reasons for this must be verified in further studies.

Background: To evaluate the clinical outcomes 12 months after systemic administration of amoxicillin (AMX) and metronidazole (MET) adjunctive to subgingival debridement (SD) in patients with severe chronic periodontitis (sChP)., Material and Methods: 102 patients with sChP were treated randomly as follows: SD within 2 consecutive days and placebo for 7 days (group A), SD+AMX+MET (both 500mg x3 times daily TID) for 3 days (group B), SD+AMX+MET (both 500mg x 3 TID) for 7 days (group C). At baseline, at 3-, 6-, and 12-months post-treatment probing pocket depth (PD), clinical attachment level (CAL), furcation involvement, bleeding on probing (BOP), full-mouth plaque score (FMPS) were determined. The reduction in the number of sites with PD≥6mm was defined as main outcome variable., Results: 75 patients completed the study. At 12 months, all three treatment groups showed statistically significant improvements (p<0.001) of mean PD, CAL, BOP and number of sites with PD≥6mm compared to baseline. Mean residual PD were statistically significantly lower and CAL gain statistically significantly greater in the two antibiotic groups as compared to placebo. While PD reductions (p = 0.012) and CAL gain (p = 0.017) were statistically significantly higher in group C compared to group A, only the 3-day AB group showed statistically significantly fewer sites with PD≥6mm at 12 m (p = 0.003). The reduction in the number of sites with PD≥6 mm (primary outcome) showed no statistical significant differences between the 3 treatment groups. However, in both antibiotic groups significantly more patients compared to the placebo group reached a low risk for disease progression at 12 months (≤4 sites with PD≥5mm)., Conclusion: At 12 months, both adjunctive antibiotic protocols resulted in statistically significantly greater clinical improvements compared to placebo.

Background: White spot lesions (WSL) frequently occur as side-effect of multibracket appliance treatment. The clinical effects of local fluoridation on post-orthodontic WSL and oral health development are however inconclusive., Objective: In vivo monitoring of clinical WSL and oral health changes in response to weekly 1.25 per cent fluoride gel application after multibracket appliance treatment., Trial Design: Randomized, single-centre, double-blind, parallel-group, placebo-controlled study., Participants: Patients with not less than 1 WSL (modified score 1 or 2) on not less than 1 upper front teeth after debonding., Interventions: Professional fluoride/placebo gel application during weeks 1-2; self-administered home application (weeks 3-24)., Outcomes: Clinical evaluation of WSL index, lesion activity, plaque index, gingival bleeding index, and decayed, missing, and filled teeth index as well as saliva buffer capacity and stimulated salivary flow rate (T0-T5)., Randomization: Random assignment to test (n = 23) or placebo group (n = 23) using a sequentially numbered list (random allocation sequence generated for 50 subjects in 25 blocks of 2 subjects each)., Recruitment: The clinical study duration lasted from March 2011 to September 2013., Blinding: Unblinding was performed after complete data evaluation., Numbers Analysed: Intention-to-treat analysis set comprised 39 participants (test: n = 21, placebo: n = 18)., Outcome: No clinical parameter except stimulated salivary flow rate (fluoride group: 1.1ml/min, placebo group: 0.74ml/min; P = 0.022) showed a statistically significant group difference after 24 weeks., Harms: Several adverse events occurred similarly frequent in both groups; none was classified as possibly related to the study product., Limitations: The number of dropouts was higher than expected and the socio-economic status was not assessed. Furthermore, the unknown level of compliance during the home application phase must be considered as limitation., Conclusion: Based on the results of this study, no clinical effect of post-orthodontic high-dose fluoride treatment on WSL and oral health changes could be detected., Registration: The study was registered with ClinicalTrials.gov (Identifier: NCT01329731)., Protocol: The protocol wasn't published before trial commencement., (© The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: White spot lesions (WSLs) are a frequent side-effect of multibracket appliance treatment. The effect of local fluoridation on post-orthodontic WSL is however inconclusive., Objective: Assessment of WSL changes in response to weekly 1.25 per cent fluoride gel application after multibracket appliance treatment., Trial Design: Randomized, single-centre, double-blind, parallel-group, placebo-controlled study., Participants: Patients with not less than 1 WSL (modified score 1 or 2) on not less than 1 upper front teeth after debonding., Interventions: Professional fluoride/placebo gel application during weeks 1-2; self-administered home application (weeks 3-24)., Outcomes: Photographic WSL assessment (dimension and luminance) of the upper front teeth (T0-T5)., Randomization: Random assignment to test (n = 23) or placebo group (n = 23) using a sequentially numbered list (random allocation sequence generated for 50 subjects in 25 blocks of 2 subjects each)., Recruitment: The clinical study duration lasted from March 2011 to September 2013., Blinding: Unblinding was performed after complete data evaluation., Numbers Analysed: Intent-to-treat analysis set comprising 39 participants (test: n = 21, placebo: n = 18)., Outcome: Dimensional WSL quantification showed limited reliability. Luminance improvement (%) of WSL, however, was seen after 6 months (test/placebo: tooth 12, 24.8/18.0; tooth 11, 38.4/35.4; tooth 21, 39.6/38.3; and tooth 22, 15.2/25.0). No statistically significant group difference existed. Data suggest that WSLs are difficult to measure with respect to reliability and repeatability and methods for monitoring WSLs in clinical trials require improvement/validation., Harms: Similar adverse events occurred in both groups; none was classified as possibly related to the study product., Limitations: The number of dropouts was higher than expected and the socio-economic status was not assessed. Furthermore, the unknown level of compliance during the home application phase must be considered as limitation., Conclusion: Based on the results of this study, no difference could be detected with respect to the development of WSL under post-orthodontic high-dose fluoride treatment., Registration: The study was registered with ClinicalTrials.gov (Identifier: NCT01329731)., Protocol: The protocol wasn't published before trial commencement., (© The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Objectives: To evaluate surface characteristics of implants after using different instruments and biofilm formation following instrumentation., Material and Methods: Thirty-five commercially available dental implants were embedded into seven plastic models, attached to a phantom head and randomly assigned to seven instrumentation groups: (1) stainless steel (SSC) or (2) titanium curettes (TC); air-polisher using glycine-based (3) perio (PP) or (4) soft (SP) powders or (5) erythritol powder (EP); and an ultrasonic device using (6) stainless steel (PS) or (7) plastic-coated instruments (PI). Half of each implant neck in each group (n = 5) was treated once (30 s), while the other half was left uninstrumented (control). An eighth (8) treatment group used a bur/polisher to smooth two implants (SM). Following instrumentation implants were rinsed (5 ml Ringer's solution), analysed under a scanning electron microscope (SEM) and subjected twice (separately) to bacterial colonization with Streptococcus gordonii (2 h) and a mixed culture (S. gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, Porphyromonas gingivalis and Tannerella forsythia; 24 h)., Results: Visual assessment of SEM pictures revealed surface modifications (smoothening to roughening) following instrumentation. These alterations differed between the instrument groups and from the control. Quantitative scoring of the photographs revealed that SSC caused a significantly rougher surface compared to other instruments (P < 0.05), except for SP (P = 0.057) and PP (P = 0.108). After bacterial colonization no significant differences (P > 0.05) were evident between instrumented or control surfaces in either culture., Conclusions: Overall, no significant differences were observed in the surface characteristics (except for SSC) or bacterial colonization based on one-time instrumentation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Obesity and periodontitis are important chronic health problems. Obesity is associated with an increased prevalence of periodontitis. Whether obesity also affects the outcome of non-surgical periodontal therapy is to date still unclear., Methods: A systematic review of studies referenced in SCOPUS, MEDLINE, PubMed, Cochrane, CINAHL, Biosis and Web of Science was performed. Titles, abstracts and finally full texts were scrutinized for possible inclusion by two independent investigators. Quality and heterogeneity of the studies were assessed and the study designs were examined. Probing pocket depth reduction was analyzed as primary surrogate parameter for therapeutic success after non-surgical periodontal therapy., Results: One-hundred-and-fifty-nine potentially qualifying studies were screened. Eight studies fulfilled the inclusion criteria and were analyzed. Three of eight studies failed to show an influence of obesity on pocket depth reduction after non-surgical therapy. The remaining five studies documented a clear negative effect on the outcome of non-surgical periodontal therapy. The finally included studies did not correspond to the highest level of quality (RCTs). Due to the heterogeneity of the data a meta-analysis was not possible., Conclusion: The literature on the effect of obesity on the treatment outcome of non-surgical periodontal therapy remains controversial. The data, however, support that obesity is not only a factor associated with poorer periodontal health but might also result in inferior response to non-surgical treatment of periodontitis.

Aim: To evaluate the effect of 3 or 7 days systemic administration of amoxicillin (AMX) and metronidazole (MET) or placebo as adjunct to non-surgical periodontal treatment in severe chronic periodontitis patients., Methods: One hundred and two patients with severe chronic periodontitis [e.g. ≥1 site with probing pocket depth (PD) ≥ 6 mm per quadrant] were randomly divided into three equally sized groups and treated with either scaling and root planing within 24 h (SRP) + placebo (Group A) or SRP + AMX + MET (both 500 mg × 3 times daily) for 3 days (Group B) or SRP + AMX + MET (both 500 mg × 3 times daily) for 7 days (Group C). PD, clinical attachment level (CAL), bleeding on probing (BOP), full-mouth plaque scores (FMPS) and gingival bleeding index (GBI) were assessed prior to treatment (baseline), and at 3 and 6 months post-treatment. The primary outcome variable was the difference (Δ) in the number of sites with PD ≥ 6 mm., Results: Ninety-one patients completed the study. At both 3 and 6 months, all three treatment protocols resulted in statistically significant improvements compared to baseline for all evaluated clinical parameters (p < 0.001). At 6 months, a statistically significantly greater reduction in the mean number of sites with PD ≥ 6 mm was observed in group B (28.62 ± 15.32 sites) and group C (30.45 ± 15.04 sites) compared to the placebo group (17.10 ± 14.68 sites). Furthermore, both the 3- and the 7-day antibiotic regimen resulted in statistically significantly higher clinical improvements compared to the placebo group (p < 0.05)., Conclusion: The present findings indicate that in patients with severe chronic periodontitis, non-surgical periodontal therapy in conjunction with a 3 or 7 days systemic administration of AMX + MET may lead to significantly greater clinical improvements compared to non-surgical therapy alone., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Malaria and anaemia which jointly account for high proportion of morbidity and mortality among young children in developing countries have been individually studied using binary regression model. We adopt geoadditive latent variable model for binary/ordinal indicators to analyze the influence of variables of different types on the morbidity among young children in Nigeria. Latent variable models allow for the analysis of multidimensional response variables that reveal the indicator's underlying relationship that are caused by the latent variables. We extend the structural model to a semi-parametric geoadditive model in order to quantify the joint spatial structure of morbidity from malaria and anaemia. Findings revealed substantial geographical variations and the generated maps can guide policy makers and donors on how to prudently utilize the scarce resources for designing more cost-effective interventions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To assess leakage of class-I restorations using a gas-enhanced permeation test (GEPT) as compared with conventional SEM or dye analysis., Materials and Methods: Pressure differences over time and penetrating water volumes were measured simultaneously in a two-chamber system (GEPT) before and after class I cavity preparation in 30 molars. Ten teeth were restored with a composite restoration without bonding (A1), a composite restoration with bonding (A2) or a ceramic indirect restoration (B). Five intact teeth served as controls (C). Another GEPT measurement was performed and impressions were taken. Teeth were subjected to thermodynamic loading (1 200 000 cycles) and final GEPT measurements and impressions were made. SEM evaluation of the marginal continuity was performed and teeth were subjected to a Fuchsin dye penetration test. Spearman's rank test was used to compare results from different tests., Results: The GEPT and SEM values did not correlate before loading (0.359, p = 0.051), but significantly correlated afterwards (0.662, p < 0.0001). The correlations between the Fuchsin dye penetration test and GEPT and SEM surface marginal analysis were significant (0.777 and 0.534, p-values < 0.0001 and 0.002, respectively)., Conclusions: SEM marginal analysis was mainly limited in reflecting the surface restoration integrity. GEPT evaluation may, therefore, serve as a tool to non-destructively assess restoration sub-surface integrity over time., Clinical Relevance: The current study provided proof that restoration margin quality does not necessarily reflect its leakage behaviour.

Background: Mercury (Hg) exposure from artisanal gold mining has adverse effects on the neuromotor function in adults. However, few studies have examined this relationship in children., Objectives: To investigate the impact of Hg exposure on children's neuromotor function., Methods: Cross-sectional data on Hg risk factors and demographics were collected from n = 288 children (response = 68.9%). Based on complete cases (CCs) (n = 130) and multiple imputations (n = 288), associations between fingernail Hg and four different neuromotor function components were calculated using multiple logistic regression adjusted for confounders., Results: Of the children, 11.1, 14.9, 63.9, and 10.4% had pathologic pure motor skills, adaptive fine motor skills, adaptive gross motor skills, and static balance, respectively. No significant association between fingernail Hg and any neuromotor component was found. However, Hg burning in the household was significantly associated with children's pathologic pure motor skills (OR 3.07 95% CI 1.03-9.18)., Conclusion: Elemental Hg exposure in the household might have adverse long-term effects on children's pure motor skills.

Background: Both CD4 count and viral load in HIV-infected persons are measured with error. There is no clear guidance on how to deal with this measurement error in the presence of missing data., Methods: We used multiple overimputation, a method recently developed in the political sciences, to account for both measurement error and missing data in CD4 count and viral load measurements from four South African cohorts of a Southern African HIV cohort collaboration. Our knowledge about the measurement error of ln CD4 and log10 viral load is part of an imputation model that imputes both missing and mismeasured data. In an illustrative example, we estimate the association of CD4 count and viral load with the hazard of death among patients on highly active antiretroviral therapy by means of a Cox model. Simulation studies evaluate the extent to which multiple overimputation is able to reduce bias in survival analyses., Results: Multiple overimputation emphasizes more strongly the influence of having high baseline CD4 counts compared to both a complete case analysis and multiple imputation (hazard ratio for >200 cells/mm vs. <25 cells/mm: 0.21 [95% confidence interval: 0.18, 0.24] vs. 0.38 [0.29, 0.48], and 0.29 [0.25, 0.34], respectively). Similar results are obtained when varying assumptions about measurement error, when using p-splines, and when evaluating time-updated CD4 count in a longitudinal analysis. The estimates of the association with viral load are slightly more attenuated when using multiple imputation instead of multiple overimputation. Our simulation studies suggest that multiple overimputation is able to reduce bias and mean squared error in survival analyses., Conclusions: Multiple overimputation, which can be used with existing software, offers a convenient approach to account for both missing and mismeasured data in HIV research.

Purpose: To assess implant leakage under static conditions as well as during and after dynamic loading. Materials and methods : Implants (Astra Tech (A), Biomet 3i (B) and Nobel Biocare (C)) were evaluated for leakage (n=8/group). Testing to assess the gas pressure change over time (hPa/min) and infiltrated fluid volume, was performed in a Gas Enhanced Permeation Test (GEPT) to qualify embedding. Implant apexes were then drilled, abutments were mounted and resin build-ups were fabricated. GEPT was reassessed. Samples were afterward mounted in a computer-controlled masticator while tested to bacterial leakage, they were daily observed for turbidity. Samples were then reassessed using GEPT. Dunnett's and Fisher's exact tests were utilized to compare implant and to analyze bacterial leakage. Results : Significant differences in GEPT values were shown after loading (p=0.034). Leakage resistance was best for B when compared to C (p=0.023). Samples with higher GEPT values demonstrated earlier bacterial leakage, occurring after 1 or 2 days (A=4, B=0, C=6) and showing favorability for implant system B (p=0.009). Conclusion : Implants leaking under static conditions had increased potential for bacterial leakage under dynamic conditions. As strongly correlating to sophisticated analytical methods, GEPT is a promising technique for assessing the overall implant system leakage resistance.

Objectives: To ensure generalizability of clinical research results, it is important to enroll a heterogeneous population that is representative of the target clinical population. Earlier studies have found regional variation in participation in human immunodeficiency virus (HIV) clinical trials, with the lowest rates seen in the southern United States. Rates of new HIV diagnoses are highest in the South, highlighting the need for in-depth understanding of disparities in clinical trial participation. We evaluated whether regional variation in study participation remains, and describe factors that facilitate or prevent HIV clinical trial participation by region., Methods: A one-time, anonymous, bilingual, self-administered survey was conducted among HIV-infected adults receiving HIV care at all 47 domestic AIDS Clinical Trials Group clinical research sites, with a goal of completing 50 surveys per site. χ(2) tests were used to evaluate differences in knowledge of and participation in HIV clinical trials by region, including Northeast, Midwest, South, and West regions. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for the effect of region on knowledge of and participation in HIV clinical trials., Results: Of 2263 completed surveys, 2125 were included in this analysis. The proportion of respondents in the South who reported knowledge of studies (66%) was significantly lower than in the Northeast (76%), Midwest (77%), and West (73%) (P = 0.001). Respondents in the South also were the least likely group to report ever having tried to or having participated in a research study (51%) compared with respondents in the Northeast (60%), Midwest (57%), and West (69%; P < 0.001). After adjusting for age, sex, education, race/ethnicity, tobacco use, and alcohol use, the odds ratio for knowledge of and participation in clinical trials for the Northeast (1.36; 95% CI 1.07-1.72) and West (1.85; 95% CI 1.39-2.45) remained significant compared with the South. African American respondents in the South were the most likely population group to report not understanding research studies (15%) as a reason for not participating, compared with the Northeast (9%), Midwest (8%), and West (6%; P < 0.001)., Conclusions: Significant regional variations in knowledge of and participation in HIV clinical trials exist. Our results suggest that increasing awareness and understanding of research studies, particularly among African Americans in the South, may facilitate HIV clinical trial participation that is more representative of the HIV-infected population across the United States.

Background: Artemether-lumefantrine and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in Cameroon. No study has yet compared the efficacy of these drugs following the WHO recommended 42-day follow-up period. The goal of this study was to compare the clinical efficacy, tolerability and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and dihydroartemisinin piperaquine (DHAP) among children aged less than ten years in two malaria-endemic ecological regions of Cameroon., Methods: A three-arm, randomized, controlled, non-inferiority trial was conducted among children of either gender aged six months (>5 kg) to ten years (n = 720) with acute uncomplicated Plasmodium falciparum infection. Parents/guardians of children provided consent prior to randomization to receive ASAQ, DHAP or AL in the ratio of 2:2:1, respectively. Treatment outcome was assessed based on standard WHO 2003 classification after 42 days of follow-up. The primary outcome was PCR-corrected day-42 cure rates. The non-inferiority, one-sided, lower limit asymptotic 97.5% confidence interval (CI) on the difference in PCR-corrected cure rates of ASAQ and DHAP when compared to AL was accepted if the lower limit of the CI was greater than -10%. Secondary outcomes were parasite and fever clearances and day 7 haemoglobin changes., Results: PCR-corrected PP cure rates of 96.7, 98.1 and 96.3, respectively, for AL, ASAQ and DHAP was observed. The lower bound of the one-sided 97.5% CI calculated around the difference between day-42 cure rate point estimates in AL and ASAQ groups, AL and DHAP groups were, -6% and -4% respectively. There were no statistical significant differences in parasite or fever clearance times between treatments, although fever clearance pattern was different between ASAQ and DHAP. No statistical significant differences were observed in the occurrence of adverse events among treatment groups., Conclusion: ASAQ and DHAP are considered safe and tolerable and are not inferior to AL in the treatment of uncomplicated P. falciparum malaria in Cameroonian children., Trial Registration: NCT01845701.

Aim: To validate a new automated dentine permeability testing platform based on pressure change measurements., Methodology: A split chamber was designed allowing for concomitant measurement of fluid permeation and pressure difference. In a first test, system reliability was assessed by interposing a solid metal disk, embedded composite resin disks, or teeth by consecutively measuring eight times under standardized conditions. Secondly, the repeatability and applicability of the method was tested in a dentine wound model by using intact third molars: Class I (2 × 5 mm) and a full occlusal preparation as well a ceramic restoration were consecutively performed and repeatedly measured eight times each. In the last test, the system detection limit as well correlation between gas pressure difference and liquid permeation were evaluated: Again, third molars were used and occlusal preparations of increasing size (2 × 5, 3 × 5, 4 × 5, and 5 × 5 mm and full occlusal preparations, respectively) were made. Data was analyzed for the linearity of measurement, and R (2) values were calculated., Results: The embedding procedure allowed for perfect separation of the two chambers, and no significant variation in repeated measurements of evaluated samples for the respective treatments (p = 0.05) was found. The detection was 0.002 hPa/min for the pressure slope and 0.0225 μl/min for the fluid infiltration, respectively. The saline volume was highly correlating to the gas pressure changes (R (2) = 0.996, p < 0.0001)., Conclusions: The presented method is a reliable and exact tool to assess dentine permeability by nondestructive and repeatable measurements., Clinical Relevance: This method is suitable for measurements and comparison of the effectiveness of dentine wounds sealing materials.

Objective: The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP., Material and Methods: Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL)., Results: Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0 ± 0.8 to 3.0 ± 0.6 mm with AB and from 5.1 ± 0.5 to 3.9 ± 0.8 mm with aPDT (p < 0.001)). AB yielded statistically significantly higher improvements in the primary outcome parameter PD (p < 0.001) when compared to aPDT. The number of pockets ≥7 mm was reduced from 141 to 3 after AB (p < 0.001) and from 137 to 45 after aPDT (p = 0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline., Conclusion: While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT., Clinical Relevance: In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.

Predictive Modeling (PM) techniques are gaining importance in the worldwide health insurance business. Modern PM methods are used for customer relationship management, risk evaluation or medical management. This article illustrates a PM approach that enables the economic potential of (cost-) effective disease management programs (DMPs) to be fully exploited by optimized candidate selection as an example of successful data-driven business management. The approach is based on a Generalized Linear Model (GLM) that is easy to apply for health insurance companies. By means of a small portfolio from an emerging country, we show that our GLM approach is stable compared to more sophisticated regression techniques in spite of the difficult data environment. Additionally, we demonstrate for this example of a setting that our model can compete with the expensive solutions offered by professional PM vendors and outperforms non-predictive standard approaches for DMP selection commonly used in the market.