Association between liver fibrosis and cognition in a nationally representative sample of older adults.

BACKGROUND AND PURPOSE: Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. METHODS: We examined the association between liver fibrosis and cognitive performance among participants aged 60 years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. RESULTS: Among 3217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (ß -0.39; 95% CI -0.58, -0.21), language fluency (ß -0.46; 95% CI -0.72, -0.21), and attention/concentration (ß -1.34; 95% CI -2.25, -0.43), but not delayed recall (ß -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. CONCLUSION: Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.

Acquired Oral Microflora of Newborns During the First 48 Hours of Life.

OBJECTIVE: To compare the oral microflora of a newborn during first hours after birth and after two days, and determine whether the newborn acquires his mother's microflora during this period. STUDY DESIGN: Saliva samples were taken from 50 newborns, on their first day of life, two days after, and from their mothers. Those samples were checked for total aerobic cultivated bacteria and mutans streptococci. RESULTS: Soon after birth, most newborns lacked any of the tested microorganisms in their oral cavity. Two days later, oral microorganisms were detected. A significant correlation was found between the total aerobic cultivated bacteria counts of the mothers, and of their newborns. CONCLUSIONS: It can be assumed, that on the first 48 hours of life, the newborn gains a major part of his oral microflora from his mother. These results might shade light on a possible to control and change the acquired microflora, at the very beginning of a human's life, creating a new, but less cariogenic flora. An accurate protocol should be examine to avoid this initial transmission during these days, while the mother and her newborn are still in the hospital, and thus might be possible to reduce caries prevalence in the future.

Salt shield: intracellular salts provide cellular protection against ionizing radiation in the halophilic archaeon, Halobacterium salinarum NRC-1.

The halophilic archaeon Halobacterium salinarum NRC-1 was used as a model system to investigate cellular damage induced by exposure to high doses of ionizing radiation (IR). Oxidative damages are the main lesions from IR and result from free radicals production via radiolysis of water. This is the first study to quantify DNA base modification in a prokaryote, revealing a direct relationship between yield of DNA lesions and IR dose. Most importantly, our data demonstrate the significance of DNA radiation damage other than strand breaks on cell survival. We also report the first in vivo evidence of reactive oxygen species scavenging by intracellular halides in H. salinarum NRC-1, resulting in increased protection against nucleotide modification and carbonylation of protein residues. Bromide ions, which are highly reactive with hydroxyl radicals, provided the greatest protection to cellular macromolecules. Modified DNA bases were repaired in 2 h post irradiation, indicating effective DNA repair systems. In addition, measurements of H. salinarum NRC-1 cell interior revealed a high Mn/Fe ratio similar to that of Deinococcus radiodurans and other radiation-resistant microorganisms, which has been shown to provide a measure of protection for proteins against oxidative damage. The work presented here supports previous studies showing that radiation resistance is the product of mechanisms for cellular protection and detoxification, as well as for the repair of oxidative damage to cellular macromolecules. The finding that not only Mn/Fe but also the presence of halides can decrease the oxidative damage to DNA and proteins emphasizes the significance of the intracellular milieu in determining microbial radiation resistance.

Current status of prognostic immunohistochemical markers for urothelial bladder cancer.

The management and prognostication of patients with urothelial carcinomas (UCs), the most common histological type of bladder cancer, is mainly based on clinicopathological parameters. Several markers have been proposed to monitor this disease, including individual cell cycle-related proteins such as p53, pRb, p16, p21 and p27. Other putative markers are the oncogene products of FGFR3 and the ErbB family, proliferation markers including Ki-67, Aurora-A and survivin and different components within the immune system. In this review, a total of 12 parameters were evaluated and their discriminatory power compared. It is concluded that, in single-marker analyses, the proliferation markers Ki-67, survivin and Aurora-A offer the best potential to predict disease progression since they were all able to demonstrate independent prognostic power in repeated studies. Markers related to the immune system (e.g. CD8+ cells, regulatory T cells and cyclooxygenase-2 expression) or oncogene products of the ErbB family and FGFR3 are less powerful predictors of outcome or have not been equally well studied. The cell cycle-related proteins p53, pRb, p16, p21 and p27 have been extensively studied, but their usefulness as single prognostic markers remains unclear. However, in multimarker analyses, these markers appear to add prognostic information, indicating that they may contribute to more accurate treatment of UC.

Comparison of urban and rural non-fatal injury: the results of a statewide survey.

OBJECTIVES: This study compared the epidemiology of non-fatal injury among urban and rural residents of Colorado. DESIGN: A stratified probability sample with random digit dial methods was used to survey Colorado residents by telephone regarding injuries experienced in the last 12 months. Questions on the cause of the injury, the activity at the time of the injury, and the place of injury were based on the Nordic Medico Statistical Committee's (NOMESCO) classification of external causes of injuries. SUBJECTS: A total of 1425 urban and 1275 rural Colorado residents aged 18 and older were interviewed. RESULTS: Age, gender, marital status, and rural residency were found to increase the odds of self reported injury. The adjusted odds ratio for self reported injury was 1.3 (95% confidence interval (CI) 1.01 to 1.68) for rural compared with urban residents. Rural residence (odds ratio 1.02, 95% CI 0.51 to 7.01) was not a risk factor for injury among the highest risk group, those who were single and never married. No differences in injury characteristics were found by urban-rural status. CONCLUSIONS: The increased odds of self reported injury among rural residents were not explained by differences in the causes of injury or other injury characteristics. The differences in the importance of rural residence in increased odds of injury by marital status warrants further understanding and may be important in the development of injury prevention programs. Based on comparison with a similar survey, the NOMESCO coding system appears to be a viable alternative survey tool for gathering information on injury characteristics.

Phylogeography of the spotted sand bass, Paralabrax maculatofasciatus: divergence of Gulf of California and Pacific Coast populations.

Have the warm tropical waters and currents of the southern Gulf of California, Mexico (also known as the Sea of Cortez), formed a barrier to gene flow, resulting in disjunct populations in the upper gulf that are isolated from the outer Pacific Coast? Phylogeographic and genetic divergences of the spotted sand bass, Paralabrax maculatofasciatus, from three Gulf of California and two outer Pacific coastal locations were tested using mitochondrial DNA (mtDNA) control region sequences. Sequence data from two congeners that are sympatrically distributed along the outer Pacific Coast, the barred sand bass, P. nebulifer, and the kelp bass, P. clathratus, were used to gauge the levels of genetic divergences. Differences among the three species and between the northern gulf and outer Pacific coastal populations of P. maculatofasciatus also were analyzed using 40 allozymic presumptive gene loci. Allozyme and mtDNA analyses each revealed many fixed differences among the species. Three significant allozymic frequency differences and two fixed mtDNA substitutions differentiated the gulf and outer Pacific coastal populations of P. maculatofasciatus. Three unique mtDNA haplotypes and three unique allozyme alleles were identified from the outer Pacific coastal population. The gulf sites contained four unique mtDNA haplotypes and six unique allozyme alleles. Partitioning of the mtDNA variation revealed that 72% of the variance occurred between the gulf and outer Pacific Coast, 20% between sampling sites in the two regions, and 8% within the sites. There appears to be little gene flow across the waters of the southern Baja Penninsula, producing divergence estimated as 120,000 to 600,000 years between the outer Pacific coastal and the Gulf of California populations. This separation level may date to a hypothesized seaway closure near La Paz, Mexico, during the mid-Pleistocene, and characterizes other fish populations. A second pattern of deeper allopatric species-level divergences in some other fishes may date to a Pliocene closure of a mid Baja Penninsular seaway. Significant differences also were discerned in P. maculatofasciatus between the San Diego and central Baja California coastal sites and between the upper/central and the lower gulf locations. Variation between locations in the two regions may be indicative of larval retention and low adult migration, which needs to be tested further.

Improving the quality of outpatient care for older patients with diabetes: lessons from a comparison of rural and urban communities.

OBJECTIVE: Our goal was to compare the quality of diabetic care received by patients in rural and urban communities. STUDY DESIGN: We performed a retrospective analysis of claims data captured by the Medicare program. POPULATION: We included all fee-for-service Medicare patients 65 years and older living in the state of Washington who had 2 or more physician encounters for diabetes care during 1994. OUTCOME MEASURES: The outcomes were the extent to which patients received 3 specific recommended services: glycated hemoglobin determination, cholesterol measurement, and eye examination. RESULTS: A total of 30,589 Medicare patients (8.4%) were considered to have diabetes; 29.1% lived in rural communities. Generalists provided most diabetic care in all locations. Patients living in small rural towns received almost half their outpatient care in larger communities. Patients living in large rural towns remote from metropolitan areas were more likely to have received the recommended tests than patients in all other groups. Patients who saw an endocrinologist at least once during the year were more likely to have received the recommended tests. CONCLUSIONS: Large rural towns may provide the best conditions for high-quality care: They are vibrant, rapidly growing communities that serve as regional referral centers and have an adequate-but not excessive-supply of both generalist and specialist physicians. Generalists provide most diabetic care in all settings, and consultation with an endocrinologist may improve adherence to guidelines.

The role of gynecologists in providing primary care to elderly women.

BACKGROUND: Federal legislation has recently been proposed to designate obstetrician-gynecologists (OBGs) as primary care physicians. The Institute of Medicine identifies care unrestricted by problem or organ system as an essential characteristic of primary care. We examined the degree to which OBGs in the state of Washington offer this aspect of primary care to their elderly patients by investigating the type and amount of nongynecologic care they provide. METHODS: Using 1994 Part B Medicare claims data for Washington residents, we identified visits made by women aged 65 years and older to OBGs (N=10,522) and 9 other types of specialists. Diagnoses were classified as in or out of the domain of care traditionally provided by each specialty. Visit volumes, proportion of out of domain visits, and the frequency of diagnoses were reported. RESULTS: Of the patient visits to obstetrician-gynecologists, 12.2% had nongynecologic diagnoses. The median percentage of nongynecologic visits for individual OBGs was 6.7%. Patients who saw OBGs received 15.4% of their overall health care from an OBG; patients who saw family physicians received 42.9% of their total health care from a family physician. CONCLUSIONS: In 1994, a small amount of the care that Washington OBGs provided to their elderly patients was for nongynecologic conditions. Studies are needed to evaluate how the practices of OBGs have changed since the 1996 implementation of a primary care requirement in obstetrics-gynecology residencies, and if adopted, how legislation designating OBGs as primary care physicians affects the health care received by elderly women.

Local health districts and the public health workforce: a case study of Wyoming and Idaho.

This study of personnel in local health departments (LHDs) focused on two predominantly rural states: Idaho and Wyoming. Although in the same region of the country, the structure of local public health is different in each state. Idaho's regionalized LHDs are relatively autonomous, whereas Wyoming's are county based, with many public health functions retained at the state level. The majority of professionals are nurses followed by environmental health workers and sanitarians, similar to data reported nationally. With increased emphasis on core public health functions of policy, assurance, and assessment, rural LHDs will be challenged to redirect the functions of their workforce.

Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion.

To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.

Differences in fertility patterns between urban and rural women in Washington State, 1983-1984 to 1993-1994.

We use data on Washington State abortions and births for 1983-1984 and 1993-1994 to analyze trends for urban and rural women, using the demographic measures total abortion and total fertility rates. These express pacing of childbearing in a single number which is simple to calculate and interpret, and is age-standardized. We find significant urban-rural differences. Total abortion rates decline and total fertility rates increase in both areas. However, the relative magnitudes of pacing decreases in abortions for rural women and increases in births for urban women are striking. The demographic measures are useful interpretive tools, and can be applied to a broad range of questions.

Quality-of-care challenges for rural health.

The purpose of this article is to examine the issue of quality of care in rural America and to help others examine this issue in a way that is consistent with the very real challenges faced by rural communities in ensuring the availability of adequate health services. Rural citizens have a right to expect that their local health care meets certain basic standards. Unless rural providers can document that the quality of local health care meets objective external standards, third-party payers might refuse to contract with rural providers, and increasingly sophisticated consumers might leave their communities for basic medical care services. To improve the measurement of health care quality in a rural setting, a number of issues specific to the rural environment must be addressed, including small sample sizes (volume and outcome issues), limited data availability, the ability to define rural health service areas, rural population preferences and the lower priority of formal quality-of-care assessment in shortage areas. Several current health policy initiatives have substantial implications for monitoring and measuring the quality of rural health services. For example, to receive community acceptance and achieve fiscal stability, critical access hospitals (CAHs) must be able to document that the care they provide is at least comparable to that of their predecessor institutions. The expectations for quality assurance activities in CAHs should consider their limited institutional resources and community preferences. As managed care extends from urban areas, there will be an inevitable collision between the ability to provide care and the ability to measure quality. As desirable as it might be to have a national standard for health care quality, this is not an attainable goal. The spectrum and content of rural health care are different from the spectrum and content of care provided in large cities. Accrediting agencies, third-party carriers and health insurance purchasers need to develop rural health care quality standards that are practical, useful and affordable.

Comparison of rate of development and rate of change for benign and malignant breast calcifications at the lumpectomy bed.

OBJECTIVE: The study purpose was to evaluate the rate of development and the rate of change for benign and malignant breast calcifications at the lumpectomy bed. MATERIALS AND METHODS: Retrospective review identified 53 new calcifications at the lumpectomy bed in patients with available mammograms and medical records. Breast Imaging Reporting and Data System (BI-RADS) categories were retrospectively assigned on the basis of initial prospective recommendation for yearly follow-up (category 2), 6-month follow-up (category 3), or biopsy (category 4 or 5). Outcomes were defined as benign for no recurrence at the lumpectomy bed on biopsy or follow-up and malignant if biopsy-proven at the lumpectomy bed. RESULTS: The median rate of development after lumpectomy was 23 months (range, 2-174 months) for benign and 39 months (range, 15-112 months) for malignant calcifications. Fifteen (28%) of 53 calcifications were classified as BI-RADS category 3. Twelve (80%) of 15 were downgraded to BI-RADS category 2 at a median follow-up of 6.5 months (range, 6-16 months); none represented recurrent disease. Three (20%) of 15 were upgraded to BI-RADS category 4 at the 6-month follow-up, one despite stability (benign) and two for increasing pleomorphism (malignant). Nine (17%) of 53 calcifications were classified as BI-RADS category 4 or 5; six (67%) of the nine were malignant and three (33%) were benign at biopsy. Twenty-nine (55%) of 53 calcifications were classified as BI-RADS category 2, none representing recurrent disease. CONCLUSION: Benign calcifications at the lumpectomy bed usually develop earlier than malignant calcifications, but the rate of development overlaps. Most calcifications initially placed in the probably benign category evolve quickly to more benign or more malignant morphology. Most calcifications heralding recurrence appear suspicious on first presentation.

Is hospitalism new? An analysis of medicare data from Washington State in 1994.

CONTEXT: Managed care, increased disease severity, and more complex treatment options may be reasons for the recent enthusiasm for "hospitalists"--physicians who specialize in the care of inpatients. It is not clear, however, whether hospitalism is a new model for caring for inpatients or merely a new description for previously existing practice patterns. PRACTICE PATTERNS EXAMINED: The proportion of physician visits occurring in the hospital before the introduction of the term hospitalists. Five specialties were examined: family/general practice, general internal medicine, cardiology, gastroenterology, and pulmonology. DATA SOURCE: 1994 Medicare Part B claims data for beneficiaries 65 years of age and older who received all of their care in Washington State. RESULTS: For the average family/general practitioner, 10% of all Medicare visits occurred in the hospital. Corresponding figures for the other specialties were 20% for general internists, 36% for cardiologists, 38% for gastroenterologists, and 45% for pulmonologists. A substantial number of physicians devoted most of their Medicare effort to inpatient care (i.e., hospital visits > 50% of total visits). If this definition were used as a proxy for hospitalism, 4% of family/general practitioners, 10% of general internists, 20% of gastroenterologists, 29% of cardiologists, and 37% of pulmonologists would have been considered hospitalists in Washington State during 1994. On the other hand, 35% of family/general practitioners, 18% of general internists, 7% of both gastroenterologists and pulmonologists, and 4% of cardiologists did not bill Medicare for any inpatient visits and could reasonably be categorized as "officists." CONCLUSION: Physicians vary considerably in the proportion of their workload that occurs in the hospital or outpatient setting. Even before the term was coined, a considerable number of physicians were de facto "hospitalists."