Clinical and microbiological analysis of subjects treated with Brånemark or AstraTech implants: a 7-year follow-up study

AIMS: To assess the impact of different implant systems on the clinical conditions and the microbiota at implants, and whether the presence of bacteria at tooth sites was predictive of the presence at implant sites. MATERIALS AND METHODS: Subjects with either AstraTech or Brånemark in function for 7 years were enrolled. Sub-gingival bacterial samples at tooth and implant sites were collected with sterile endodontic paper points, and analyzed by the checkerboard DNA-DNA hybridization method (40 species). RESULTS: Fifty-four subjects, 27 supplied with AstraTech (n=132 implants) and 27 with Brånemark (n=102) implants, were studied. Test tooth sites had significantly less evidence of bleeding on probing (P<0.001) and presence of plaque (P<0.001) than implant test sites. Implant sites presented with deeper probing pocket depth than tooth sites (mean difference: 1.1 mm, standard error of differences: 0.08, 95% confidence intervals (CI): 0.9-1.3, P<0.001). Tannerella forsythia (P<0.05), Capnocytophaga sputigena (P<0.05), Actinomyces israelii (P<0.05) and Lactobacillus acidophilus (P<0.05) were found at higher levels at tooth surfaces. No differences in bacterial load for any species were found between the two implant systems. The odds of being present/absent at tooth and implants sites were only significant for Staphylococcus aureus [odds ratio (OR): 5.2 : 1, 95% CI: 1.4-18.9, P<0.01]. CONCLUSIONS: After 7 years in function, implants presented with deeper probing depths than teeth. S. aureus was commonly present at both teeth and implants sites. S. aureus at tooth sites was predictive of also being present at implant sites.

Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study

Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

Periodontal pathogens and associated factors in aggressive periodontitis: results 5-17 years after active periodontal therapy

OBJECTIVES To assess the association between presence of periodontal pathogens and recurrence of disease in patients with aggressive periodontitis (AgP) after active periodontal therapy (APT) and further influencing factors. MATERIAL & METHODS Microbiological samples were taken from 73 patients with AgP 5-17 years after APT at 292 sites (deepest site per quadrant). Real-time polymerase chain reactions were used to detect the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Uni- and multivariate analyses evaluated the associations between pathogens and recurrence of disease, smoking and adjunctive antibiotic therapy. RESULTS At re-examination A. actinomycetemcomitans could be detected in six patients (8.2%), P. gingivalis in 24 (32.9%), T. forsythia in 31 (42.5%) and T. denticola in 35 (48.0%). Increased levels of T. forsythia and T. denticola at re-examination were significantly associated with recurrence of disease in multivariate analyses (OR: 12.72, p < 0.001; OR 5.55, p = 0.002 respectively). Furthermore, high counts of T. denticola were found in patients with increased percentage of sites with clinical attachment levels (CAL) ≥ 6 mm compared to those with low counts (13.8% versus 3.2%, p = 0.005). CONCLUSION In patients with recurrence of disease T. forsythia and T. denticola were detected more frequently and in higher counts. Furthermore, T. denticola was found more frequently in patients with increased CAL.

Crystal structures of isotypic poly[bis(benzimidazolium) [tetra-μ-iodido-stannate(II)]] and poly[bis(5,6-difluorobenzimidazolium) [tetra-μ-iodido-stannate(II)]]

The isostructural title compounds, {(C7H7N2)2[SnI4]}n, (1), and {(C7H5F2N2)2[SnI4]}n, (2), show a layered perovskite-type structure composed of anionic {[SnI4]2-}n sheets parallel to (100), which are decorated on both sides with templating benzimidazolium or 5,6-di­fluoro­benzimidazolium cations, respectively. These planar organic heterocycles mainly form N-H...I hydrogen bonds to the terminal I atoms of the corner-sharing [SnI6] octa­hedra (point group symmetry 2) from the inorganic layer, but not to the bridging ones. This is in contrast to most of the reported structures of related compounds where ammonium cations are involved. Here hydrogen bonding to both types of iodine atoms and thereby a distortion of the inorganic layers to various extents is observed. For (1) and (2), all Sn-I-Sn angles are linear and no out-of-plane distortions of the inorganic layers occur, a fact of relevance in view of the material properties. The arrangement of the aromatic cations is mainly determined through the direction of the N-H...I hydrogen bonds. The coherence between organic bilayers along [100] is mainly achieved through van der Waals inter­actions.

The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

UNLABELLED The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.

Prospective clinical study evaluating the long-time adjunctive use of chlorhexidine after one-stage full-mouth SRP

OBJECTIVES: Scaling and root planing are the causal procedure in the treatment of periodontitis. Many attempts have been made to improve the outcome. The aim of this study was to verify the influence of the extended use of chlorhexidine after one-stage full-mouth (FM) SRP in patients with chronic periodontitis on the clinical outcome after 3 months. METHODS: Eighty-one patients with pockets > or =5 mm were treated by FM. All patients rinsed additionally with 0.2% chlorhexidine (CHX) twice daily over 3 months. Plaque index, bleeding on probing, probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and after 1 and 3 months. RESULTS: In the test group, all variables were significantly improved after 1 and 3 months. Mean reduction of PD and CAL gain was 2.25 +/- 1.08 and 1.67 +/- 1.08 after 1 and 2.99 +/- 1.11 and 2.33 +/- 1.31 after 3 months respectively. CONCLUSIONS: Over 3 months of extended use of CHX mouth rinse after SRP showed slightly but statistically significant better results.

Prognostic factors in apical surgery with root-end filling: a meta-analysis

INTRODUCTION: Apical surgery has seen continuous development with regard to equipment and surgical technique. However, there is still a shortage of evidence-based information regarding healing determinants. The objective of this meta-analysis was to review clinical articles on apical surgery with root-end filling in order to assess potential prognostic factors. METHODS: An electronic search of PubMed and Cochrane databases was performed in 2008. Only studies with clearly defined healing criteria were included, and data for at least two categories per prognostic factor had to be reported. Prognostic factors were divided into patient-related, tooth-related, or treatment-related factors. The reported percentages of healed teeth ("the healed rate") were pooled per category. The statistical method of Mantel-Haenszel was applied to estimate the odds ratios and their 95% confidence intervals. RESULTS: With regard to tooth-related factors, the following categories were significantly associated with higher healed rates: cases without preoperative pain or signs, cases with good density of root canal filling, and cases with absence or size < or = 5 mm of periapical lesion. With regard to treatment-related factors, cases treated with the use of an endoscope tended to have higher healed rates than cases without the use of an endoscope. CONCLUSIONS: Although the clinician may be able to control treatment-related factors (by choosing a certain technique), patient- and tooth-related factors are usually beyond the surgeon's power. Nevertheless, patient- and tooth-related factors should be considered as important prognostic determinants when planning or weighing apical surgery against treatment alternatives.

Rarely selected distractors in high stakes medical multiple-choice examinations and their recognition by item authors: A simulation and survey

Background Many medical exams use 5 options for multiple choice questions (MCQs), although the literature suggests that 3 options are optimal. Previous studies on this topic have often been based on non-medical examinations, so we sought to analyse rarely selected, 'non-functional' distractors (NF-D) in high stakes medical examinations, and their detection by item authors as well as psychometric changes resulting from a reduction in the number of options. Methods Based on Swiss Federal MCQ examinations from 2005-2007, the frequency of NF-D (selected by <1% or <5% of the candidates) was calculated. Distractors that were chosen the least or second least were identified and candidates who chose them were allocated to the remaining options using two extreme assumptions about their hypothetical behaviour: In case rarely selected distractors were eliminated, candidates could randomly choose another option - or purposively choose the correct answer, from which they had originally been distracted. In a second step, 37 experts were asked to mark the least plausible options. The consequences of a reduction from 4 to 3 or 2 distractors - based on item statistics or on the experts' ratings - with respect to difficulty, discrimination and reliability were modelled. Results About 70% of the 5-option-items had at least 1 NF-D selected by <1% of the candidates (97% for NF-Ds selected by <5%). Only a reduction to 2 distractors and assuming that candidates would switch to the correct answer in the absence of a 'non-functional' distractor led to relevant differences in reliability and difficulty (and to a lesser degree discrimination). The experts' ratings resulted in slightly greater changes compared to the statistical approach. Conclusions Based on item statistics and/or an expert panel's recommendation, the choice of a varying number of 3-4 (or partly 2) plausible distractors could be performed without marked deteriorations in psychometric characteristics.

Properties of low-threshold motor axons in the human median nerve

This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na(+) conductance, I(NaP). Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I(NaP). Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I(h)) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.

Predicting the transition from acute to persistent low back pain

BACKGROUND: Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. AIMS: To identify factors that influence the progression of acute LBP to the persistent state at an early stage. METHODS: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices 'working condition', 'depression and maladaptive cognitions' and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as 'depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary prevention.

Predicting the transition from acute to persistent low back pain

BACKGROUND: Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. AIMS: To identify factors that influence the progression of acute LBP to the persistent state at an early stage. METHODS: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices 'working condition', 'depression and maladaptive cognitions' and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as 'depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary prevention.

Frequency of and predictors for patient-reported medical and medication errors in Switzerland

OBJECTIVES: To analyse the frequency of and identify risk factors for patient-reported medical errors in Switzerland. The joint effect of risk factors on error-reporting probability was modelled for hypothetical patients. METHODS: A representative population sample of Swiss citizens (n = 1306) was surveyed as part of the Commonwealth Fund’s 2010 lnternational Survey of the General Public’s Views of their Health Care System’s Performance in Eleven Countries. Data on personal background, utilisation of health care, coordination of care problems and reported errors were assessed. Logistic regression analysis was conducted to identify risk factors for patients’ reports of medical mistakes and medication errors. RESULTS: 11.4% of participants reported at least one error in their care in the previous two years (8% medical errors, 5.3% medication errors). Poor coordination of care experiences was frequent. 7.8% experienced that test results or medical records were not available, 17.2% received conflicting information from care providers and 11.5% reported that tests were ordered although they had been done before. Age (OR = 0.98, p = 0.014), poor health (OR = 2.95, p = 0.007), utilisation of emergency care (OR = 2.45, p = 0.003), inpatient-stay (OR = 2.31, p = 0.010) and poor care coordination (OR = 5.43, p <0.001) are important predictors for reporting error. For high utilisers of care that unify multiple risk factors the probability that errors are reported rises up to p = 0.8. CONCLUSIONS: Patient safety remains a major challenge for the Swiss health care system. Despite the health related and economic burden associated with it, the widespread experience of medical error in some subpopulations also has the potential to erode trust in the health care system as a whole.

Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Methods Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period. Results From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56). Conclusions The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

Development and validation of decision rules to guide frequency of monitoring CD4 cell count in HIV-1 infection before starting antiretroviral therapy

Background Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study. Methodology/Principal Findings We built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ≥5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold. Conclusions/Significance Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.