Patient characteristics and testing over COVID-19 waves 1 and 2 from the first German COVID-19 testing unit in Munich, Germany.

BACKGROUND: In Munich, the first German case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected on 27 January 2020 at the Division of Infectious Diseases and Tropical Medicine of the University Hospital LMU Munich (DIDTM), and consecutively the Covid Testing Unit was established. Germany advocated several public health measures to control the outbreak. This study investigates the effects of measures on health service utilization in the public, which in turn can alter case numbers and test positivity rates. METHOD: Our retrospective observational study was conducted to determine the effects of public health measures on the utilization of a testing facility and positivity rates from the first operational COVID-19 testing facility in Munich for waves 1 and 2 over a period of 14 months. This was accomplished by comparing trends in client characteristics including age, gender, symptoms, and socio-demographic aspects over time to non-pharmaceutical measures in Germany. To depict trend changes in testing numbers over time, we developed a negative binomial model with multiple breakpoints. RESULTS: In total 9861 tests were conducted on 6989 clients. The clients were mostly young (median age: 34), female (60.58%), and asymptomatic (67.89%). Among those who tested positive for SARS-CoV-2, 67.72% were symptomatic while the percentage was 29.06% among those who tested negative. There are other risk factors, but a SARS-CoV-2-positive colleague at work is the most prominent factor. Trend changes in the clients' testing numbers could be attributed to the implementation of various public health measures, testing strategies, and attitudes of individuals toward the pandemic. However, test positivity rates did not change substantially during the second wave of the pandemic. CONCLUSION: We could show that implementation or changes in public health measures have a strong effect on the utilization of testing facilities by the general public, which independently of the true epidemiological background situation can result in changing test numbers.

Modelling of a triage scoring tool for SARS-COV-2 PCR testing in health-care workers: data from the first German COVID-19 Testing Unit in Munich.

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.

Clinical, microbiological, and immunological effects of 3- or 7-day systemic antibiotics adjunctive to subgingival instrumentation in patients with aggressive (Stage III/IV Grade C) periodontitis: A randomized placebo-controlled clinical trial.

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 > .05). All investigated periodontopathogens and pro-inflammatory host-derived markers were statistically significantly reduced without differences between the treatments (p > .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.

Sociodemographic and clinical determinants of in-facility case fatality rate for 938 adult Ebola patients treated at Sierra Leone Ebola treatment center.

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.

Bacterial supernatants elevate glucose-dependent insulin secretion in rat pancreatic INS-1 line and islet ß-cells via PI3K/AKT signaling.

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 ß-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-1ß, 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-1ß, 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 ß-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 ß-cell compensatory response.

Epidemiological characteristics, clinical manifestations, and treatment outcome of 139 paediatric Ebola patients treated at a Sierra Leone Ebola treatment center.

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.

Effect of toothpaste containing amine fluoride and stannous chloride on the reduction of dental plaque and gingival inflammation. A randomized controlled 12-week home-use study.

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.

Cancer survival in people with AIDS: A population-based study from São Paulo, Brazil.

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.

Bootstrap inference when using multiple imputation.

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.

Clinical and laboratory evaluation of the effects of different treatment modalities on titanium healing caps: a randomized, controlled clinical trial.

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.

Antibacterial Effect and Substantivity of Toothpaste Slurries In Vivo.

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.

Influence of different instrumentation modalities on the surface characteristics and biofilm formation on dental implant neck, in vitro.

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.

Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part I: photographic data evaluation.

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.

Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part II: clinical data evaluation.

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.

Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic administration of amoxicillin and metronidazole in severe chronic periodontitis patients. A placebo-controlled randomized clinical study.

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.

Evaluation of a novel repetitive gas-enhanced permeation test for restoration leakage determination after thermo-mechanical loading.

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.

Influence of obesity on the outcome of non-surgical periodontal therapy - a systematic review.

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.

Simultaneous Treatment of Missing Data and Measurement Error in HIV Research Using Multiple Overimputation.

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.

Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children.

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.

Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life.

Although work-related asthma and allergies are a huge burden for society, investigation of occupational exposures in early work life using an unexposed reference group is rare. Thus, the present analyses aimed to assess the potential impact of occupational exposure and other risk factors on the prevalence of work-related sensitisation and incidence of allergic rhinitis/asthma using a population-based approach and taking into account an unexposed reference group. In SOLAR (Study on Occupational Allergy Risks) II, German participants of ISAAC (International Study of Asthma and Allergies in Childhood) phase II were followed from childhood (9-11 years) until early adulthood (19-24 years). Data on 1570 participants were available to fit predictive models. Occupational exposure was not statistically significantly associated with disease prevalence/incidence. Sensitisation in childhood, parental asthma, environmental tobacco smoke exposure during puberty, sex and study location were statistically significant predictors of outcome. Our results indicate that occupational exposure is of little relevance for work-related sensitisation prevalence and allergic rhinitis/asthma incidence in early work life, while other risk factors can be used to improve career guidance for adolescents. Further research on the role of a potential healthy hire effect and the impact of longer exposure duration is needed.