Okuläre Pulsamplitude als biometrischer Messwert in der Glaukomdiagnostik

Zusammenfassung: Hintergrund: Die dynamische Konturtonometrie (DCT) ermöglicht direkte transkorneale Messungen des Augeninnendrucks und der okulären Pulsamplitude (OPA). Ziel dieser Studie war es, herauszufinden, ob die OPA als biometrischer Messwert Aussagen über verschiedene Glaukomformen erlaubt. Patienten und Methoden: Es wurden 441 Augen von 222Patienten in die Studie aufgenommen. Zur Druckmessung dienten die DCT und ein Applanationstonometer nach Goldmann. Ergebnisse: Die mittlere OPA betrug 3,1±1,4mmHg. Augen mit okulärer Hypertension (3,6±1,3mmHg) zeigten signifikant höhere Werte als gesunde Augen (3,1±1,4mmHg) und solche mit Niederdruckglaukom (2,9±1,4mmHg). Nach erfolgreicher Trabekulektomie wurden signifikant tiefere Werte (2,4±1,3mmHg) als bei Gesunden gemessen. Schlussfolgerung: Die OPA scheint diverse Formen des Glaukoms zu charakterisieren, könnte aber auch direkt von der Höhe des Augendrucks abhängen. Es muss weiter abgeklärt werden, ob sie einen prädiktiven Faktor in der Diagnose und der Verlaufsbeurteilung des Glaukoms darstell

Pharmacoepidemiology and Drug Safety's special issue on validation studies

Administrative claims and other routinely collected data provide the foundation for many drug utilization, safety, and effectiveness studies. These databases provide a rich source of timely health care information on large, well‐defined populations. Yet information contained in these databases is generally captured using standardized systems, summarizing complex medical histories, clinical diagnoses, and services and therapies provided to patients. Thus, carefully designed validation studies that evaluate the accuracy of coded algorithms to identify health‐related exposures, outcomes, and covariates against a reference standard are an essential component for demonstrating the validity of their use for research purposes

Insights into different results from different causal contrasts in the presence of effect-measure modification

Purpose: Both propensity score (PS) matching and inverse probability of treatment weighting (IPTW) allow causal contrasts, albeit different ones. In the presence of effect-measure modification, different analytic approaches produce different summary estimates. Methods: We present a spreadsheet example that assumes a dichotomous exposure, covariate, and outcome. The covariate can be a confounder or not and a modifier of the relative risk (RR) or not. Based on expected cell counts, we calculate RR estimates using five summary estimators: Mantel-Haenszel (MH), maximum likelihood (ML), the standardized mortality ratio (SMR), PS matching, and a common implementation of IPTW. Results: Without effect-measure modification, all approaches produce identical results. In the presence of effect-measure modification and regardless of the presence of confounding, results from the SMR and PS are identical, but IPTW can produce strikingly different results (e.g., RR = 0.83 vs. RR = 1.50). In such settings, MH and ML do not estimate a population parameter and results for those measures fall between PS and IPTW. Conclusions: Discrepancies between PS and IPTW reflect different weighting of stratum-specific effect estimates. SMR and PS matching assign weights according to the distribution of the effect-measure modifier in the exposed subpopulation, whereas IPTW assigns weights according to the distribution of the entire study population. In pharmacoepidemiology, contraindications to treatment that also modify the effect might be prevalent in the population, but would be rare among the exposed. In such settings, estimating the effect of exposure in the exposed rather than the whole population is preferable

Counterpoint: Keeping the Demons at Bay When Handling Time-Varying Exposures-Beyond Avoiding Immortal Person-Time

The potential for immortal time bias is pervasive in epidemiologic studies with left truncation or time-varying exposures. Unlike other biases in epidemiologic research (e.g., measurement bias, confounding due to unmeasured factors, and selection based on unmeasured predictors of the outcome), immortal time bias can and should be avoided by the correct assignment of person-time during follow up. However, even when handing person-time correctly, allowing late entry into a study or into an exposure group can open the door to more insidious sources of bias, some of which we explore here. Clear articulation of the study question, including the treatment plans of interest, can provide navigation around these sources of bias and elucidate the assumptions needed for inference given the available data. Here, we use simulated data to illustrate the assumptions required under various approaches to estimate the effect of a time-varying treatment and describe how these assumptions relate to the assumptions necessary to estimate single sample rates and risks in settings with censoring and truncation

Real-world evidence: the devil is in the detail

Much has been written about real-world evidence (RWE), a concept that offers an understanding of the effects of healthcare interventions using routine clinical data. The reflection of diverse real-world practices is a double-edged sword that makes RWE attractive but also opens doors to several biases that need to be minimised both in the design and analytical phases of non-experimental studies. Additionally, it is critical to ensure that researchers who conduct these studies possess adequate methodological expertise and ability to accurately implement these methods. Critical design elements to be considered should include a clearly defined research question using a causal inference framework, choice of a fit-for-purpose data source, inclusion of new users of a treatment with comparators that are as similar as possible to that group, accurately classifying person-time and deciding censoring approaches. Having taken measures to minimise bias ‘by design’, the next step is to implement appropriate analytical techniques (for example propensity scores) to minimise the remnant potential biases. A clear protocol should be provided at the beginning of the study and a report of the results after, including caveats to consider. We also point the readers to readings on some novel analytical methods as well as newer areas of application of RWE. While there is no one-size-fits-all solution to evaluating RWE studies, we have focused our discussion on key methods and issues commonly encountered in comparative observational cohort studies with the hope that readers are better equipped to evaluate non-experimental studies that they encounter in the future

Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study

Aims—Dipeptidyl-peptidase-4 inhibitors (DPP-4i) have been implicated with an increased pancreatic cancer risk. We therefore compared pancreatic cancer incidence and diagnostic work-up among initiators of DPP-4i versus sulfonylureas (SU) and thiazolidinediones (TZD). Methods—Medicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4i, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Diagnostic work-up was compared using risk ratios (RR). RESULTS—In the DPP-4i vs SU comparison, there were 18,179 DPP4i initiators of which 26 developed pancreatic cancer (follow-up time interquartile range 5–18 months). In the DPP-4i vs TZD comparison there were 29,366 DPP-4i initiators and 52 developed pancreatic cancer. The hazard of pancreatic cancer with DPP-4i was lower relative to SU (HR=0.6, CI 0.4–0.9) and similar to TZD (HR=1.0, CI 0.7–1.4). Excluding first 6 months of follow-up to reduce the potential for reverse causality did not alter results. Probability of diagnostic work-up post-initiation among DPP-4i initiators (79.3%) was similar to TZD (74.1%) (RR=1.06, CI 1.05–1.07) and SU (74.6%) (RR=1.06, CI1.05–1.07). The probability of diagnostic workup pre-index was ~80% for all cohorts. Conclusion—Though limited by sample size and the observed duration of treatment in the US, our well-controlled population based study suggests no increased short-term pancreatic cancer risk with DPP-4i relative to SU or TZD

Magnetic resonance imaging analysis of the bioabsorbable Milagro™ interference screw for graft fixation in anterior cruciate ligament reconstruction

Ligament graft fixation with bioabsorbable interference screws is a standard procedure in cruciate ligament replacement. Previous screw designs may resorb incompletely, and can cause osteolysis and sterile cysts despite being implanted for several years. The aim of this study was to examine the in vivo degradation and biocompatibility of the new Milagro™ interference screw (Mitek, Norderstedt, Germany). The Milagro™ interference screw is made of 30% ß-TCP (TriCalcium phosphate) and 70% PLGA (Poly-lactic-co-glycolic acid). In the period between June 2005 and February 2006, 38 patients underwent graft fixation with Milagro™ screws in our hospital. Arthroscopic ACL reconstruction was performed using hamstring tendon grafts in all the patients. MR imaging was performed on 12 randomly selected patients out of the total of 38 at 3, 6 and 12 months after surgery. During the examination, the volume loss of the screw, tunnel enlargement, presence of osteolysis, fluid lines, edema and postoperative screw replacement by bone tissue were evaluated. There was no edema or signs of inflammation around the bone tunnels. At 3, 6 and 12 months, the tibial screws showed an average volume loss of 0, 8.1% (±7.9%) and 82.6% (±17.2%, P < 0.05), respectively. The femoral screws showed volume losses of 2.5% (±2.1%), 31.3% (±21.6%) and 92.02% (±6.3%, P < 0.05), respectively. The femoral tunnel enlargement was 47.4% (±43.8%) of the original bone tunnel volume after 12 months, and the mean tunnel volume of the tibial tunnel was −9.5% (±58.1%) compared to the original tunnel. Bone ingrowth was observed in all the patients. In conclusion, the resorption behaviour of the Milagro™ screw is closely linked to the graft healing process. The screws were rapidly resorbed after 6 months and, at 12 months, only the screw remnants were detectable. Moreover, the Milagro™ screw is biocompatible and osteoconductive, promoting bone ingrowth during resorption. Tunnel enlargement is not prevented in the first months but is reduced by bone ingrowth after 12 months

Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors

Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence

Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier's gangrene

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier's gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning. Methods We used data from IBM MarketScan (2013-2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions. Results We identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51-0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04-1.74) to 1.14 (0.86-1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53-6.11) and inpatient diagnoses only (aHR 4.58; 0.99-21.21). Conclusions No evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG. Trial registration number EUPAS Register Number 30018