Genes to blood pressure: The effects of variation in genes of the renin-angiotensin system on the hormonal and renal control of blood pressure

Objective. Essential hypertension affects 25% of the US adult population and is a leading contributor to morbidity and mortality. Because BP is a multifactorial phenotype that resists simple genetic analysis, intermediate phenotypes within the complex network of BP regulatory systems may be more accessible to genetic dissection. The Renin-Angiotensin System (RAS) is known to influence intermediate and long-term blood pressure regulation through alterations in vascular tone and renal sodium and fluid resorption. This dissertation examines associations between renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) gene variation and interindividual differences in plasma hormone levels, renal hemodynamics, and BP homeostasis.^ Methods. A total of 150 unrelated men and 150 unrelated women, between 20.0 and 49.9 years of age and free of acute or chronic illness except for a history of hypertension (11 men and 7 women, all off medications), were studied after one week on a controlled sodium diet. RAS plasma hormone levels, renal hemodynamics and BP were determined prior to and during angiotensin II (Ang II) infusion. Individuals were genotyped by PCR for a variable number tandem repeat (VNTR) polymorphism in REN, and for the following restriction fragment length polymorphisms (RFLP): AGT M235T, ACE I/D, and AT1 A1166C. Associations between clinical measurements and allelic variation were examined using multiple linear regression statistical models.^ Results. Women homozygous for the AT1 1166C allele demonstrated higher intracellular levels of sodium (p = 0.044). Men homozygous for the AGT T235 allele demonstrated a blunted decrement in renal plasma flow in response to Ang II infusion (p = 0.0002). There were no significant associations between RAS gene variation and interindividual variation in RAS plasma hormone levels or BP.^ Conclusions. Rather than identifying new BP controlling genes or alleles, the study paradigm employed in this thesis (i.e., measured genes, controlled environments and interventions) may provide mechanistic insight into how candidate genes affect BP homeostasis. ^

INFLUENCE OF A CLINIC BASED IMMUNIZATION INFORMATION SYSTEM ON INFANT IMMUNIZATIONS

This study focuses on the impact of a clinic-based intervention program on the immunization status of limited-income urban children. The intervention program consisted of an information session for clinic health care providers and the placement of individualized immunization information labels on clinic notes at the time of each visit. The degree of impact of the intervention on immunization administration was ascertained through a comparison of two similar groups of infants born in the same months of the year immediately before (N = 201) and after (N = 203) the information session and initiation of the labeling system. The timeliness of administration of each diphtheria, pertussis, tetanus and trivalent oral polio vaccine (DPT/TOPV) in the first year series of three was compared pre- to postintervention. Significantly more third immunizations were given the postintervention subjects within ten days of the recommended time of application ( p = .0361). Life table analysis indicated that the probability of an infant's passing one year of age without the administration of the third immunization decreased for postintervention infants (p = .0515). The intervention was most successful in assuring administration of the series of immunizations in those infants who were seen by the health care provider for at least 50% of their first year visits. Results indicate that minor changes in the format of information given a relatively continuous provider can increase completion of immunization series in infants. ^

Financial impact of the Medicare prospective payment system on long term acute care hospitals

Objective. Long Term Acute Care Hospitals (LTACs) are subject to Medicare rules because they accept Medicare and Medicaid patients. In October 2002, Medicare changed the LTAC reimbursement formulas, from a cost basis system to a Prospective Payment System (PPS). This study examines whether the PPS has negatively affected the financial performance of the LTAC hospitals in the period following the reimbursement change (2003-2006), as compared to the period prior to the change (1999-2003), and if so, to what extent. This study will also examine whether the PPS has resulted in a decreased average patient length of stay (LOS) in the LTAC hospitals for the period of 2003-2006 as compared to the prior period of 1999-2003, and if so, to what extent. ^ Methods. The study group consists of two large LTAC hospital systems, Kindred Healthcare Inc. and Select Specialty Hospitals of Select Medical Corporation. Financial data and operational indicators were reviewed, tabulated and dichotomized into two groups, covering the two periods: 1999-2002 and 2003-2006. The financial data included net annual revenues, net income, revenue per patient per day and profit margins. It was hypothesized that the profit margins for the LTAC hospitals were reduced because of the new PPS. Operational indicators, such as annual admissions, annual patient days, and average LOS were analyzed. It was hypothesized that LOS for the LTAC hospitals would have decreased. Case mix index, defined as the weighted average of patients’ DRGs for each hospital system, was not available to cast more light on the direction of LOS. ^ Results. This assessment found that the negative financial impacts did not materialize; instead, financial performance improved during the PPS period (2003-2006). The income margin percentage under the PPS increased for Kindred by 24%, and for Select by 77%. Thus, the study’s working hypothesis of reduced income margins for the LTACs under the PPS was contradicted. As to the average patient length of stay, LOS decreased from 34.7 days to 29.4 days for Kindred, and from 30.5 days to 25.3 days for Select. Thus, on the issue of LTAC shorter length of stay, the study’s working hypothesis was confirmed. ^ Conclusion. Overall, there was no negative financial effect on the LTAC hospitals during the period of 2003-2006 following Medicare implementation of the PPS in October 2002. On the contrary, the income margins improved significantly. ^ During the same period, LOS decreased following the implementation of the PPS. This was consistent with the LTAC hospitals’ pursuit of financial incentives.^

Financial impact of the Medicare prospective payment system on long term acute care hospitals

Objective. Long Term Acute Care Hospitals (LTACs) are subject to Medicare rules because they accept Medicare and Medicaid patients. In October 2002, Medicare changed the LTAC reimbursement formulas, from a cost basis system to a Prospective Payment System (PPS). This study examines whether the PPS has negatively affected the financial performance of the LTAC hospitals in the period following the reimbursement change (2003–2006), as compared to the period prior to the change (1999–2003), and if so, to what extent. This study will also examine whether the PPS has resulted in a decreased average patient length of stay (LOS) in the LTAC hospitals for the period of 2003–2006 as compared to the prior period of 1999-2003, and if so, to what extent. ^ Methods. The study group consists of two large LTAC hospital systems, Kindred Healthcare Inc. and Select Specialty Hospitals of Select Medical Corporation. Financial data and operational indicators were reviewed, tabulated and dichotomized into two groups, covering the two periods: 1999–2002 and 2003–2006. The financial data included net annual revenues, net income, revenue per patient per day and profit margins. It was hypothesized that the profit margins for the LTAC hospitals were reduced because of the new PPS. Operational indicators, such as annual admissions, annual patient days, and average LOS were analyzed. It was hypothesized that LOS for the LTAC hospitals would have decreased. Case mix index, defined as the weighted average of patients’ DRGs for each hospital system, was not available to cast more light on the direction of LOS. ^ Results. This assessment found that the negative financial impacts did not materialize; instead, financial performance improved during the PPS period (2003–2006). The income margin percentage under the PPS increased for Kindred by 24%, and for Select by 77%. Thus, the study’s working hypothesis of reduced income margins for the LTACs under the PPS was contradicted. As to the average patient length of stay, LOS decreased from 34.7 days to 29.4 days for Kindred, and from 30.5 days to 25.3 days for Select. Thus, on the issue of LTAC shorter length of stay, the study’s working hypothesis was confirmed. ^ Conclusion. Overall, there was no negative financial effect on the LTAC hospitals during the period of 2003–2006 following Medicare implementation of the PPS in October 2002. On the contrary, the income margins improved significantly. ^ During the same period, LOS decreased following the implementation of the PPS. This was consistent with the LTAC hospitals’ pursuit of financial incentives. ^