Effects of congressional modernization laws on public access to innovative medical device technologies

The Federal Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid (CMS) play key roles in making Class III, medical devices available to the public, and they are required by law to meet statutory deadlines for applications under review. Historically, both agencies have failed to meet their respective statutory requirements. Since these failures affect patient access and may adversely impact public health, Congress has enacted several “modernization” laws. However, the effectiveness of these modernization laws has not been adequately studied or established for Class III medical devices. ^ The aim of this research study was, therefore, to analyze how these modernization laws may have affected public access to medical devices. Two questions were addressed: (1) How have the FDA modernization laws affected the time to approval for medical device premarket approval applications (PMAs)? (2) How has the CMS modernization law affected the time to approval for national coverage decisions (NCDs)? The data for this research study were collected from publicly available databases for the period January 1, 1995, through December 31, 2008. These dates were selected to ensure that a sufficient period of time was captured to measure pre- and post-modernization effects on time to approval. All records containing original PMAs were obtained from the FDA database, and all records containing NCDs were obtained from the CMS database. Source documents, including FDA premarket approval letters and CMS national coverage decision memoranda, were reviewed to obtain additional data not found in the search results. Analyses were conducted to determine the effects of the pre- and post-modernization laws on time to approval. Secondary analyses of FDA subcategories were conducted to uncover any causal factors that might explain differences in time to approval and to compare with the primary trends. The primary analysis showed that the FDA modernization laws of 1997 and 2002 initially reduced PMA time to approval; after the 2002 modernization law, the time to approval began increasing and continued to increase through December 2008. The non-combined, subcategory approval trends were similar to the primary analysis trends. The combined, subcategory analysis showed no clear trends with the exception of non-implantable devices, for which time to approval trended down after 1997. The CMS modernization law of 2003 reduced NCD time to approval, a trend that continued through December 2008. This study also showed that approximately 86% of PMA devices do not receive NCDs. ^ As a result of this research study, recommendations are offered to help resolve statutory non-compliance and access issues, as follows: (1) Authorities should examine underlying causal factors for the observed trends; (2) Process improvements should be made to better coordinate FDA and CMS activities to include sharing data, reducing duplication, and establishing clear criteria for “safe and effective” and “reasonable and necessary”; (3) A common identifier should be established to allow tracking and trending of applications between FDA and CMS databases; (4) Statutory requirements may need to be revised; and (5) An investigation should be undertaken to determine why NCDs are not issued for the majority of PMAs. Any process improvements should be made without creating additional safety risks and adversely impacting public health. Finally, additional studies are needed to fully characterize and better understand the trends identified in this research study.^

The use of the computerized and revised vital record in conducting etiologic studies on neural tube defects

The purpose of this study was to evaluate the adequacy of computerized vital records in Texas for conducting etiologic studies on neural tube defects (NTDs), using the revised and expanded National Centers for Health Statistics vital record forms introduced in Texas in 1989.^ Cases of NTDs (anencephaly and spina bifida) among Harris County (Houston) residents were identified from the computerized birth and death records for 1989-1991. The validity of the system was then measured against cases ascertained independently through medical records and death certificates. The computerized system performed poorly in its identification of NTDs, particularly for anencephaly, where the false positive rate was 80% with little or no improvement over the 3-year period. For both NTDs the sensitivity and predictive value positive of the tapes were somewhat higher for Hispanic than non-Hispanic mothers.^ Case control studies were conducted utilizing the tape set and the independently verified data set, using controls selected from the live birth tapes. Findings varied widely between the data sets. For example, the anencephaly odds ratio for Hispanic mothers (vs. non-Hispanic) was 1.91 (CI = 1.38-2.65) for the tape file, but 3.18 (CI = 1.81-5.58) for verified records. The odds ratio for diabetes was elevated for the tape set (OR = 3.33, CI = 1.67-6.66) but not for verified cases (OR = 1.09, CI = 0.24-4.96), among whom few mothers were diabetic. It was concluded that computerized tapes should not be solely relied on for NTD studies.^ Using the verified cases, Hispanic mother was associated with spina bifida, and Hispanic mother, teen mother, and previous pregnancy terminations were associated with anencephaly. Mother's birthplace, education, parity, and diabetes were not significant for either NTD.^ Stratified analyses revealed several notable examples of statistical interaction. For anencephaly, strong interaction was observed between Hispanic origin and trimester of first prenatal care.^ The prevalence was 3.8 per 10,000 live births for anencephaly and 2.0 for spina bifida (5.8 per 10,000 births for the combined categories). ^

The prevalence of bulimia nervosa and bulimic behaviors among university students in Texas

This cross-sectional study examined by questionnaire the prevalence of bulimia nervosa and bulimic behaviors in a sample of 1175 undergraduate students enrolled in two state-supported universities in Texas. In one university, the student population was predominantly white; in the other, it was predominantly black. Fifty-nine percent of the respondents were female and 41% were male. Information regarding age, sex, ethnicity, college major, college year, marital status, housing arrangements, religion, socioeconomic status, height, weight, dieting behaviors, and family history of alcoholism, drug abuse, and depression was collected. Bulimia status was assessed using the Revised Bulimia Test (BULIT-R), which is based on the DSM-III-R criteria for bulimia nervosa. Only 1.3% of the females and 0.4% of the males were classified as having bulimia nervosa. The prevalence of bulimic behaviors was considerably higher; 6.4% of the females and 3.6% of the males were classified as having bulimic behaviors. Univariate analysis showed the following factors to be significantly associated with bulimic behaviors: female gender, single marital status, high BMI, a family history of alcoholism, drug abuse, or depression, and certain dieting behaviors. In the present study, ethnicity did not prove to be a significant factor associated with bulimia nervosa or bulimic behaviors. Multivariate analysis showed that, in comparison to normal/underweight individuals, the odds of having bulimic behaviors for severely overweight subjects were 2.23 (95% CI: 1.43, 3.50). Students who were dieting at the time of the study were 3.22 times (95% CI: 2.05, 5.06) as likely to have bulimic behaviors as were students who had never dieted. This study concludes there is a need to distinguish between bulimia nervosa and bulimic behaviors when estimating prevalence of a population. ^

Evaluating the Utility of Clinical Criteria for the Identification of Lynch Syndrome among Endometrial Cancer Patients

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting. Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic medical record, and all tumors were tested for expression of the DNA mismatch repair proteins through immunohistochemistry. Tumors exhibiting loss of MSH2, MSH6 and PMS2 were designated as probable Lynch Syndrome (PLS). For tumors exhibiting immunohistochemical loss of MLH1, we used the PCR-based MLH1 methylation assay to delineate PLS tumors from sporadic tumors. Samples lacking methylation of the MLH1 promoter were also designated as PLS. The sensitivity and specificity for SGO criteria for detecting PLS tumors was calculated. We compared clinical and pathologic features of sporadic tumors and PLS tumors. A simplified cost-effectiveness analysis was also performed comparing the direct costs of utilizing SGO criteria vs. universal tumor testing. Results: In our cohort, 43/408 (10.5%) of endometrial carcinomas were designated as PLS. The sensitivity and specificity of SGO criteria to identify PLS cases were 32.7 and 77%, respectively. Multivariate analysis of clinical and pathologic parameters failed to identify statistically significant differences between sporadic and PLS tumors with the exception of tumors arising from the lower uterine segment. These tumors were more likely to occur in PLS tumors. Cost-effectiveness analysis showed clinical criteria and universal testing strategies cost $6,235.27/PLS case identified and $5,970.38/PLS case identified, respectively. Conclusions: SGO 5-10% criteria successfully identify PLS cases among women who are young or have significant family history of LS related tumors. However, a larger proportion of PLS cases occurring at older ages with less significant family history are not detected by this screening strategy. Compared to SGO clinical criteria, universal tumor testing is a cost effective strategy to identify women presenting with endometrial cancer who are at elevated risk for having LS.

Revised depth scale, splice tie points and chron boundaries of ODP Hole 151-907A and Site 162-907

The magnetic polarity stratigraphy at Site 907 obtained from the shipboard pass-through magnetometer and from discrete samples is readily interpretable back to the onset of the Gilbert Chron (5.89 Ma). From this level to the base of the section at ~14 Ma, the interpretation is corroborated by silicoflagellate datums with predictable correlation to polarity chrons. The resulting magnetostratigraphic interpretation differs from those proposed in the Leg 151 (Hole 907A) and 162 (Holes 907B and 907C) Initial Reports volumes. An important hiatus in the 7-10 Ma interval at Site 907 caused sedimentation to slow or cease for ~2.7 m.y. We have revised the shipboard correlation among the three holes at Site 907, resulting in a new composite section splice and recalculation of composite depths. For Site 985, magnetostratigraphic interpretation is possible down to ~150 meters below seafloor (mbsf) (C3An/C3Ar) at ~6 Ma. There are no useful biostratigraphic datums from Site 985 to support this interpretation; however, the interpretation is supported by the correlation of Sites 985 and 907 using natural gamma data from the shipboard multisensor track. Below ~150 mbsf at Site 985, drilling-related deformation at the onset of extended core barrel drilling precluded magnetostratigraphic interpretation.

Classification criteria and commercial profile re-definition of the Family Farm Agriculture in Chile, Maule region

In Chile, small-scale farmers are classified according to old approaches from 1993 that do not include changes occurred in the last two decades. Maule is the region with most rural population in Chile which represents a significant stratum for development, innovation and competitiveness. This study explores a new approach of small-scale farmers -associated with Family Farm Agriculture (AFC) - classification in Chile and it describes a commercial profile or AFC-1 for famers of the Maule Region. A Cluster analysis to determine AFC-1 farmers is used. The analysis includes four association variables: Total Assets, Farm Income, Production Costs and Management Indicators. The results suggest that 16.4% of the farmers have a commercial profile and they could stay out support provided by the National Institute for Agricultural Development (INDAP). This group of farmers would not belong to AFC in short terms. This fact could bring restriction to AFC-1 farmers such as lack of credit access, less investment incentives and technical assistance. Thus, it would expect low process of technology adoption and welfare improvement. New agrarian policies must be warranted to support this important group of famers with a commercial profile.

Revised age models and foraminiferal records obtained for the Last Interglacial period in six marine sediment cores

The dataset contains the revised age models and foraminiferal records obtained for the Last Interglacial period in six marine sediment cores: - the Southern Ocean core MD02-2488 (age model, sea surface temperatures, benthic d18O and d13C for the period 136-108 ka), - the North Atlantic core MD95-2042 (age model, planktic d18O, benthic d18O and d13C for the period 135-110 ka), - the North Atlantic core ODP 980 (age model, planktic d18O, sea surface temperatures, seawater d18O, benthic d18O and d13C, ice-rafted detritus for the period 135-110 ka), - the North Atlantic core CH69-K09 (age model, planktic d18O, sea surface temperatures, seawater d18O, benthic d18O and d13C, ice-rafted detritus for the period 135-110 ka), - the Norwegian Sea core MD95-2010 (age model, percentage of Neogloboquadrina pachyderma sinistral, sea surface temperatures, benthic d18O, ice-rafted detritus for the period 134-110 ka), - the Labrador Sea core EW9302-JPC2 (age model, percentage of Neogloboquadrina pachyderma sinistral, sea surface temperatures, benthic d18O for the period 134-110 ka).

XRF data, magnetic susceptibility, greyscale values and revised depths of sediments from ODP Leg 154 sites

The distinctly cyclic sediments recovered during ODP Leg 154 played an important role in constructing the astronomical time scale and associated astro(bio)chronology for the Miocene, and in deciphering ocean-climate history. The accuracy of the timescale critically depends on the reliability of the shipboard splice used for the tuning and on the tuning itself. New high-resolution colour- and magnetic susceptibility core scanning data supplemented with limited XRF-data allow improvement of the stratigraphy. The revised composite record results in an improved astronomical age model for ODP Site 926 between 5 and 14.4 Ma. The new age model is confirmed by results of complex amplitude demodulation of the precession and obliquity related cycle patterns. Different values for tidal dissipation are applied to improve the fit between the sedimentary cycle patterns and the astronomical solution. Due to the improved stratigraphy and tuning, supported by the results of amplitude demodulation, the revised time scale yields more reliable age estimates for planktic foraminiferal and calcareous nannofossil events. The results of this study highlight the importance of stratigraphy for timescale construction.

Guidance and counseling in Latin America : General considerations about the criteria of coherence, cooperation and quality

La Orientación en América Latina, como campo de formación profesional y en comparación con Europa y Estados Unidos, es una actividad de reciente aceptación en los medios académicos. La misma se ha caracterizado por una constante evolución en su afán de adaptarse a los nuevos cambios y transformaciones sociales, políticas y económicas que se suceden en el continente latinoamericano. En esta ponencia se presenta un panorama general acerca de la Orientación en América Latina. Las principales consideraciones formuladas se relacionan con cuatro dimensiones: a) la dimensión política pública, donde se presentan la situación actual y las propuestas al respecto; b) la dimensión contextual que hace referencia a la formación del orientador y los diferentes escenarios de acción; c) la dimensión organizacional que se relaciona con la provisión de este servicio, y d) la dimensión metodológica donde se desarrollan los principales aspectos relacionados con la práctica de la Orientación.

Criteria of election of postgraduate courses in graduated students of technological/ humanistic/ artistic professions : Subjective and contextual involvements to arrive at the conclusion of them

El aumento en la cantidad de estudios de posgrado y de sus cursantes derivados de la demanda por mayores credenciales académicas en lo laboral y por la búsqueda personal para especializarse profesionalmente, es un fenómeno observado en Argentina desde mediados de los años 90. Obtener el título final de estos estudios resulta un porcentaje muy inferior en relación al número de sus inscriptos. Tales motivos focalizaron nuestra atención para analizar tanto los criterios de elección del posgrado como las condiciones contextuales y subjetivas para alcanzar la titulación. Este estudio, de tipo cualitativo, investiga en tres carreras de Especialización que se cursan en diferentes Universidades nacionales , los aspectos de su organización y estilo propuesto para cursar y lograr la finalización de los estudios, así como las motivaciones de la elección de cursantes y egresados en tres ramas diferentes: artística, humanística y tecnológica. El conocimiento sobre la lógica de la organización y la particularidad del objeto de estudio de cada carrera permite analizar diferencias y semejanzas entre ellas aportando algunas propuestas para considerar en programas de formación; mientras que los trayectos de cursantes y egresados explican aspectos subjetivos que intervienen en la finalización o no del posgrado.

(Table 22-30) Revised composite depth scales of IODP Sites 320-U1331, U1332, U1333, U1334 and ODP Sites 199-1218, 199-1219, 199-1220

Integrated Ocean Drilling Program (IODP) Expedition 320 recovered high-quality paleomagnetic records with over 800 dated reversals and decimeter-scale cyclic sediments which provide an outstanding framework to inter-calibrate major fossil groups and refine magnetic polarity chrons for the early Miocene, the entire Oligocene and the late Eocene Epoch. In order to reconstruct the climate history of the Equatorial Pacific one of the major objectives of the Pacific Equatorial Age Transect (PEAT) is the compilation of a Cenozoic Megasplice which integrates all available bio-, chemo-, and magnetostratigraphic data including key records from Ocean Drilling Program (ODP) Leg 199. Here we present extended post-cruise refinements of the shipboard composite depth scales and composite records of IODP Expedition 320 Sites U1331, U1332, U1333, U1334 as well as ODP Leg 199 Sites 1218, 1219 and 1220. The revised composite records were used to perform a site-to-site correlation and integration of Leg 199 and Exp. 320 sites. Based on this decimeter scale correlation a high resolution integrated paleomagnetic and biostratigraphic framework for the Equatorial Pacific is established covering the time from 20 to 40 Ma. This unprecedented sedimentary compendium from the Equatorial Pacific will be the backbone for paleoceanographic reconstructions for the late Paleogene.

Revised composite depth scales for ODP sites 198-1209, 198-1210 and 198-1211, Shatsky Rise

We present new revised composite depth scales for Ocean Drilling Program Leg 198 Sites 1209, 1210, and 1211, drilled at Shatsky Rise in the western Pacific Ocean. Reinterpretation of high-resolution physical property data, with the main focus on magnetic susceptibility as the primary parameter for hole-to-hole correlation, revealed that the shipboard composite records had to be revised below 124.87 meters composite depth (mcd) for Site 1209, below 142.45 mcd for Site 1210, and below 88.64 mcd for Site 1211. The revised composite records comprise Paleogene and Cretaceous sediments at all three sites. As a result of the additional adjustments, the revised mcd records of Sites 1209 and 1210 are 13.48 and 2.69 m longer than the original spliced records, respectively. The original splice of Site 1211 has undergone minor adjustments only to match those of Sites 1209 and 1210. Moreover, detailed correlation of sections outside the new spliced records enable samples already taken to be placed into the new revised composite depth scale.