Impingement adversely affects 10-year survivorship after periacetabular osteotomy for DDH

BACKGROUND Although periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) provides conceptual advantages compared with other osteotomies and reportedly is associated with joint survivorship of 60% at 20 years, the beneficial effect of proper acetabular reorientation with concomitant arthrotomy and creation of femoral head-neck offset on 10-year hip survivorship remains unclear. QUESTIONS/PURPOSES We asked the following questions: (1) Does the 10-year survivorship of the hip after PAO improve with proper acetabular reorientation and a spherical femoral head; (2) does the Merle d'Aubigné-Postel score improve; (3) can the progression of osteoarthritis (OA) be slowed; and (4) what factors predict conversion to THA, progression of OA, or a Merle d'Aubigné-Postel score less than 15 points? METHODS We retrospectively reviewed 147 patients who underwent 165 PAOs for DDH with two matched groups: Group I (proper reorientation and spherical femoral head) and Group II (improper reorientation and aspherical femoral head). We compared the Kaplan-Meier survivorship, Merle d'Aubigné-Postel scores, and progression of OA in both groups. A Cox regression analysis (end points: THA, OA progression, or Merle d'Aubigné-Postel score less than 15) was performed to detect factors predicting failure. The minimum followup was 10 years (median, 11 years; range, 10-14 years). RESULTS An increased survivorship was found in Group I. The Merle d'Aubigné-Postel score did not differ. Progression of OA in Group I was slower than in Group II. Factors predicting failure included greater age, lower preoperative Merle d'Aubigné-Postel score, and the presence of a Trendelenburg sign, aspherical head, OA, subluxation, postoperative acetabular retroversion, excessive acetabular anteversion, and undercoverage. CONCLUSIONS Proper acetabular reorientation and the creation of a spherical femoral head improve long-term survivorship and decelerate OA progression in patients with DDH.

Surgical hip dislocation for treatment of femoroacetabular impingement: factors predicting 5-year survivorship.

BACKGROUND Patients with femoroacetabular impingement (FAI) often develop pain, impaired function, and progression of osteoarthritis (OA); this is commonly treated using surgical hip dislocation, femoral neck and acetabular rim osteoplasty, and labral reattachment. However, results with these approaches, in particular risk factors for OA progression and conversion to THA, have varied. QUESTIONS/PURPOSES We asked if patients undergoing surgical hip dislocation with labral reattachment to treat FAI experienced (1) improved hip pain and function; and (2) prevention of OA progression; we then determined (3) the survival of the hip at 5-year followup with the end points defined as the need for conversion to THA, progression of OA by at least one Tönnis grade, and/or a Merle d'Aubigné-Postel score less than 15; and calculated (4) factors predicting these end points. METHODS Between July 2001 and March 2003, we performed 146 of these procedures in 121 patients. After excluding 35 patients (37 hips) who had prior open surgery and 11 patients (12 hips) who had a diagnosis of Perthes disease, this study evaluated the 75 patients (97 hips, 66% of the procedures we performed during that time) who had a mean followup of 6 years (range, 5-7 years). We used the anterior impingement test to assess pain, the Merle d'Aubigné-Postel score to assess function, and the Tönnis grade to assess OA. Survival and predictive factors were calculated using the method of Kaplan and Meier and Cox regression, respectively. RESULTS The proportion of patients with anterior impingement decreased from 95% to 17% (p < 0.001); the Merle d'Aubigné-Postel score improved from a mean of 15 to 17 (p < 0.001). Seven hips (7%) showed progression of OA and another seven hips (7%) converted to THA Survival free from any end point (THA, progression of OA, or a Merle d'Aubigné-Postel < 15) of well-functioning joints at 5 years was 91%; and excessive acetabular rim trimming, preoperative OA, increased age at operation, and weight were predictive factors for the end points. CONCLUSIONS At 5-year followup, 91% of patients with FAI treated with surgical hip dislocation, osteoplasty, and labral reattachment showed no THA, progression of OA, or an insufficient clinical result, but excessive acetabular trimming, OA, increased age, and weight were associated with early failure. To prevent early deterioration of the joint, excessive rim trimming or trimming of borderline dysplastic hips has to be avoided.

Influence of contact points on the performance of caries detection methods in approximal surfaces of primary molars: an in vivo study

This in vivo study aimed to evaluate the influence of contact points on the approximal caries detection in primary molars, by comparing the performance of the DIAGNOdent pen and visual-tactile examination after tooth separation to bitewing radiography (BW). A total of 112 children were examined and 33 children were selected. In three periods (a, b, and c), 209 approximal surfaces were examined: (a) examiner 1 performed visual-tactile examination using the Nyvad criteria (EX1); examiner 2 used DIAGNOdent pen (LF1) and took BW; (b) 1 week later, after tooth separation, examiner 1 performed the second visual-tactile examination (EX2) and examiner 2 used DIAGNOdent again (LF2); (c) after tooth exfoliation, surfaces were directly examined using DIAGNOdent (LF3). Teeth were examined by computed microtomography as a reference standard. Analyses were based on diagnostic thresholds: D1: D 0 = health, D 1 –D 4 = disease; D2: D 0 , D 1 = health, D 2 –D 4 = disease; D3: D 0 –D 2 = health, D 3 , D 4 = disease. At D1, the highest sensitivity/specificity were observed for EX1 (1.00)/LF3 (0.68), respectively. At D2, the highest sensitivity/ specificity were observed for LF3 (0.69)/BW (1.00), respectively. At D3, the highest sensitivity/specificity were observed for LF3 (0.78)/EX1, EX2 and BW (1.00). EX1 showed higher accuracy values than LF1, and EX2 showed similar values to LF2. We concluded that the visual-tactile examination showed better results in detecting sound surfaces and approximal caries lesions without tooth separation. However, the effectiveness of approximal caries lesion detection of both methods was increased by the absence of contact points. Therefore, regardless of the method of detection, orthodontic separating elastics should be used as a complementary tool for the diagnosis of approximal noncavitated lesions in primary molars.

Similarities and differences between physician and non-physician acupuncturists in using diagnostic methods - an explorative study

Purpose: Acupuncture is one of the complementary medicine therapies with the greatest demand in Switzerland and many other countries in the West and in Asia. Over the past decades, the pool of scientific literature in acupuncture has markedly increased. The diagnostic methods upon which acupuncture treatment is based, have only been addressed sporadically in scientific journals. The goal of this study is to assess the use of different diagnostic methods in the acupuncture practices and to investigate similarities and differences in using these diagnostic methods between physician and non-physician acupuncturists. Methods: 44 physician acupuncturists with certificates of competence in acupuncture – traditional chinese medicine (TCM) from ASA (Assoziation Schweizer Ärztegesellschaften für Akupunktur und Chinesische Medizin: the Association of Swiss Medical Societies for Acupuncture and Chinese Medicine) and 33 non-physician acupuncturists listed in the EMR (Erfahrungsmedizinisches Register: a national register, which assigns a quality label for CAM therapists in complementary and alternative medicine) in the cantons Basel-Stadt and Basel-Land were asked to fill out a questionnaire on diagnostic methods. The responder rate was 46.8% (69.7% non-physician acupuncturists and 29, 5% physician acupuncturists). Results: The results show that both physician and non-physician acupuncturists take patients’ medical history (94%), use pulse diagnosis (89%), tongue diagnosis (83%) and palpation of body and ear acupuncture points (81%) as diagnostic methods to guide their acupuncture treatments. Between the two groups, there were significant differences in the diagnostic tools being used. Physician acupuncturists do examine their patients significantly more often with western medical methods (p<.05) than this is the case for nonphysician acupuncturists. Non-physician acupuncturists use pulse diagnosis more often than physicians (p<.05). A highly significant difference was observed in the length of time spent with collecting patients’ medical history, where nonphysician acupuncturists clearly spent more time (p<.001). Conclusion: Depending on the educational background of the acupuncturist, different diagnostic methods are used for making the diagnosis. Especially the more time consuming methods like a comprehensive anamnesis and pulse diagnosis are more frequently employed by non-physician practitioners. Further studies will clarify if these results are valid for Switzerland in general, and to what extent the differing use of diagnostic methods has an impact on the diagnosis itself and on the resulting treatment methods, as well as on the treatment success and the patients’ satisfaction.

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Clinical end points in coronary stent trials: a case for standardized definitions

BACKGROUND: Although most clinical trials of coronary stents have measured nominally identical safety and effectiveness end points, differences in definitions and timing of assessment have created confusion in interpretation. METHODS AND RESULTS: The Academic Research Consortium is an informal collaboration between academic research organizations in the United States and Europe. Two meetings, in Washington, DC, in January 2006 and in Dublin, Ireland, in June 2006, sponsored by the Academic Research Consortium and including representatives of the US Food and Drug Administration and all device manufacturers who were working with the Food and Drug Administration on drug-eluting stent clinical trial programs, were focused on consensus end point definitions for drug-eluting stent evaluations. The effort was pursued with the objective to establish consistency among end point definitions and provide consensus recommendations. On the basis of considerations from historical legacy to key pathophysiological mechanisms and relevance to clinical interpretability, criteria for assessment of death, myocardial infarction, repeat revascularization, and stent thrombosis were developed. The broadly based consensus end point definitions in this document may be usefully applied or recognized for regulatory and clinical trial purposes. CONCLUSION: Although consensus criteria will inevitably include certain arbitrary features, consensus criteria for clinical end points provide consistency across studies that can facilitate the evaluation of safety and effectiveness of these devices.

Patient-reported outcomes in meta-analyses - part 2: methods for improving interpretability for decision-makers

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complimented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95%CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27%relative reduction in the mean depression score).

Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy.

PURPOSE Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max). METHODS We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method). RESULTS For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10-20% by the two-point method and by up to 30% with a large variation by the Bayesian method. CONCLUSIONS The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8-10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.

Lipid- and mechanosensitivities of sodium/hydrogen exchangers analyzed by electrical methods.

Sodium/hydrogen exchangers (NHEs) are ubiquitous ion transporters that serve multiple cell functions. We have studied two mammalian isoforms, NHE1 (ubiquitous) and NHE3 (epithelial-specific), by measuring extracellular proton (H+) gradients during whole-cell patch clamp with perfusion of the cell interior. Maximal Na(+)-dependent H+ fluxes (JH+) are equivalent to currents >20 pA for NHE1 in Chinese hamster ovary fibroblasts, >200 pA for NHE1 in guinea pig ventricular myocytes, and 5-10 pA for NHE3 in opossum kidney cells. The fluxes are blocked by an NHE inhibitor, ethylisopropylamiloride, and are absent in NHE-deficient AP-1 cells. NHE1 activity is stable with perfusion of nonhydrolyzable ATP [adenosine 5'-(beta,gamma-imido)triphosphate], is abolished by ATP depletion (2 deoxy-D-glucose with oligomycin or perfusion of apyrase), can be restored with phosphatidylinositol 4,5-bisphosphate, and is unaffected by actin cytoskeleton disruption (latrunculin or pipette perfusion of gelsolin). NHE3 (but not NHE1) is reversibly activated by phosphatidylinositol 3,4,5-trisphosphate. Both NHE1 and NHE3 activities are disrupted in giant patches during gigaohm seal formation. NHE1 (but not NHE3) is reversibly activated by cell shrinkage, even at neutral cytoplasmic pH without ATP, and inhibited by cell swelling. NHE1 in Chinese hamster ovary fibroblasts (but not NHE3 in opossum kidney cells) is inhibited by agents that thin the membrane (L-alpha-lysophosphatidylcholine and octyl-beta-D-glucopyranoside) and activated by cholesterol enrichment, which thickens membranes. Expressed in AP-1 cells, however, NHE1 is insensitive to these agents but remains sensitive to volume changes. Thus, changes of hydrophobic mismatch can modulate NHE1 but do not underlie its volume sensitivity.

Permittivity measurements of porous matter in support of investigations of the surface and interior of 67P/Churyumov-Gerasimenko

Aims. Permittivity measurements on porous samples of volcanic origin have been performed in the 0.05-190 GHz range under laboratory conditions in support of the Rosetta mission to comet 67P/Churyumov-Gerasimenko, specifically with the MIRO radiometric experiment and CONSERT radar experiment. Methods. The samples were split into several subsamples with different size ranges covering a few mu m to 500 mu m. Bulk densities of the subsamples were estimated to be in the 800 to 1500 kg/m(3) range. The porosities were in the range of 48% to 65%. From 50 MHz to 6 GHz and at 190 GHz, permittivity has been determined with a coaxial cell and with a quasi-optical bench, respectively. Results. Without taking into account the volume-scattering effect at 190 GHz, the real part of the permittivity, normalized by the bulk density, is in the range of 2.1 to 2.6. The results suggest that the real part of the permittivity of an ice-free dust mantle covering the nucleus is in the 1.5-2.2 range at 190 GHz. From these values, a lower limit for the absorption length for the millimeter receiver of MIRO has been estimated to be between 0.6 and 2 cm, in agreement with results obtained from MIRO in September 2014. At frequencies of interest for CONSERT experiment, the real part of the permittivity of a suspected ice-free dust mantle should be below 2.2. It may be in the range of 1.2 to 1.7 for the nucleus, in agreement with first CONSERT results, taking into account a mean temperature of 110 K and different values for the dust-to-ice volumetric ratio. Estimations of contributions of the different parameters to the permittivity variation may indicate that the porosity is the main parameter.

Can we constrain the interior structure of rocky exoplanets from mass and radius measurements?

Aims. We present an inversion method based on Bayesian analysis to constrain the interior structure of terrestrial exoplanets, in the form of chemical composition of the mantle and core size. Specifically, we identify what parts of the interior structure of terrestrial exoplanets can be determined from observations of mass, radius, and stellar elemental abundances. Methods. We perform a full probabilistic inverse analysis to formally account for observational and model uncertainties and obtain confidence regions of interior structure models. This enables us to characterize how model variability depends on data and associated uncertainties. Results. We test our method on terrestrial solar system planets and find that our model predictions are consistent with independent estimates. Furthermore, we apply our method to synthetic exoplanets up to 10 Earth masses and up to 1.7 Earth radii, and to exoplanet Kepler-36b. Importantly, the inversion strategy proposed here provides a framework for understanding the level of precision required to characterize the interior of exoplanets. Conclusions. Our main conclusions are (1) observations of mass and radius are sufficient to constrain core size; (2) stellar elemental abundances (Fe, Si, Mg) are principal constraints to reduce degeneracy in interior structure models and to constrain mantle composition; (3) the inherent degeneracy in determining interior structure from mass and radius observations does not only depend on measurement accuracies, but also on the actual size and density of the exoplanet. We argue that precise observations of stellar elemental abundances are central in order to place constraints on planetary bulk composition and to reduce model degeneracy. We provide a general methodology of analyzing interior structures of exoplanets that may help to understand how interior models are distributed among star systems. The methodology we propose is sufficiently general to allow its future extension to more complex internal structures including hydrogen- and water-rich exoplanets.