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A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.

Objective: Therapeutic goals for chronic mental disorders like major depressive disorder (MDD) and schizophrenia have evolved in parallel with the growing medical knowledge about the course and treatment of these disorders. Although the knowledge base regarding the clinical course of ADHD, a chronic psychiatric disorder, has evolved beyond symptomatic improvement and short-term treatment response, long-term goals, such as functional remission, have not yet been clearly defined. Method: A PubMed literature search was conducted to investigate the therapeutic goals of pharmacologic treatment referenced in the published literature from January 1998 through February 2010 using the following commonly used ADHD treatments as keywords: amphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine, and clonidine. This search was then combined with an additional search that included the following outcome keywords: remission, relapse, remit, response, normal, normalization, recovery, and effectiveness. Results: Our search identified 102 publications. The majority (88.2% [90/102]) of these contained predefined criteria for treatment response. Predefined criteria for normalization and remission and/or relapse were presented in 4.9% (5/102), 12.7% (13/102), and 3.9% (4/102) of publications, respectively. There was a lack of consistency between the instruments used to measure outcomes as well as the criteria used to define treatment response, normalization, and remission as well as relapse. Conclusion: The therapeutic goals in treating ADHD should address optimal treatment outcomes that go beyond modest reductions of ADHD symptoms to include syndromatic, symptomatic, and functional remission. Future work should focus on reliable and valid tools to measure these outcomes in the clinical trial setting.

Background— Congestion is a primary driver of symptoms in patients with acute heart failure, and relief of congestion is a critical goal of therapy. Monitoring of response to therapy through the assessment of daily weights and net fluid loss is the current standard of care, yet the relationship between commonly used markers of decongestion and both patient reported symptom relief and clinical outcomes are unknown. Methods and Results— We performed a retrospective analysis of the randomized clinical trial, Diuretic Optimization Strategy Evaluation in Acute Heart Failure (DOSE-AHF), enrolling patients hospitalized with a diagnosis of acute decompensated heart failure. We assessed the relationship among 3 markers of decongestion at 72 hours—weight loss, net fluid loss, and percent reduction in serum N terminal B-type natriuretic peptide (NT-proBNP) level—and relief of symptoms as defined by the dyspnea visual analog scale area under the curve. We also determined the relationship between each marker of decongestion and 60-day clinical outcomes defined as time to death, first rehospitalization or emergency department visit. Mean age was 66 years, mean ejection fraction was 35%, and 27% had ejection fraction ≥50%. Of the 3 measures of decongestion assessed, only percent reduction in NT-proBNP was significantly associated with symptom relief ( r =0.13; P =0.04). There was no correlation between either weight loss or net fluid loss and symptom relief, ( r =0.04; P =0.54 and r =0.07; P =0.27, respectively). Favorable changes in each of the 3 markers of decongestion were associated with improvement in time to death, rehospitalization, or emergency department visit at 60 days (weight: hazard ratio, 0.91; 95% confidence interval, 0.85–0.97 per 4 lbs; weight lost; fluid hazard ratio, 0.94; 95% confidence interval, 0.90–0.99 per 1000 mL fluid loss; NT-proBNP hazard ratio, 0.95; 95% confidence interval, 0.91–0.99 per 10% reduction). These associations were unchanged after multivariable adjustment with the exception that percent reduction in NT-proBNP was no longer a significant predictor (hazard ratio, 0.97; 95% confidence interval, 0.93–1.02). The rates of death, HF hospitalization, or emergency department visit at 60 days for patients with 0, 1, 2, and 3 markers of decongestion (above the median) were 67%, 64%, 46%, and 38%, respectively (log rank P value=0.05). Figure. Relationship between number of markers of decongestion above median* and time to 60-day risk of emergency department (ED) visit, rehospitalization, or death. *Median net fluid loss, 3.8 L; median net weight loss, 6.5 lbs; median percent reduction in N terminal B-type natriuretic peptide 24.3%. Conclusions— Weight loss, fluid loss, and NT-proBNP reduction at 72 hours are poorly correlated with dyspnea relief. However, favorable improvements in each of the 3 markers were associated with improved clinical outcomes at 60 days. These data suggest the need for ongoing research to understand the relationships among symptom relief, congestion, and outcomes in patients with acute decompensated heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00577135.

Abstract The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.