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K L Cox

Publications and source records attributed to K L Cox.

At least 19 recordsLinked to original sources
PubMed2006

Adolescent non-adherence: prevalence and consequences in liver transplant recipients.

Few studies have examined the prevalence, demographic variables and adverse consequences associated with non-adherence to immunosuppressive therapy in the adolescent liver transplant population. Our hypothesis is that a significant proportion of adolescent liver transplant recipients exhibit non-adherence to medical regimens and that certain demographic and medical condition-related characteristics can be identified as potential predictors of non-adherent behavior. Furthermore, non-adherence leads to a greater incidence of morbidity and mortality in this population as compared with the adherent subset of adolescent patients. We reviewed the charts of 97 patients from 1987 to 2002 who by December of 2002 had survived at least 1 yr post-transplant and were followed by the Pediatric Liver Transplant Service at any point during their adolescent period (ages of 12-21). Non-adherence was defined as documentation of a report of non-adherence by a patient, parent or healthcare provider that was recorded in the patient's legal medical record. Descriptive statistics were used to determine the prevalence, demographic variables and adverse outcomes associated with non-adherence to immunosuppressive therapy. Categorical variables were analyzed using the chi-square test or the Fisher exact probability test. The unpaired Student's t-test was used to analyze the continuous variable of age at transplant. Using the inclusion criteria, a total of 97 patients represented the study sample of whom 37 subjects (38.1%) were defined as non-adherent and 60 (61.8%) were adherent. Non-adherent subjects were more likely to be female, older (>18 yr) and from a single-parent household. There was no significant difference in immunosuppressive regimen between non-adherent and adherent patients. Non-adherence was significantly (p<0.025) associated with lower socioeconomic status (SES), older age at transplant (p<0.005, 95% CI: -5.5 to -.99, Student's t-test) and episodes of late acute rejection (p<.001). Non-adherence was also significantly associated with re-transplantation and death secondary to chronic rejection by the Fisher exact test (p<0.006 and p<0.05, respectively). Non-adherence to immunosuppressive therapy is a prevalent problem that is correlated with certain demographic and medical condition-related risk factors and more frequent adverse consequences in the adolescent liver transplant population. The greater incidence of late acute rejection, death and re-transplantation owing to chronic rejection in non-adherent patients suggests that non-adherence is significantly associated with an increased risk of morbidity and mortality. Further investigation to identify patients at greatest risk for non-adherence is necessary to design the most effective intervention to increase patient survival and well being.

Adolescent↗
PubMed2003

Controlled comparison of retention and adherence in home- vs center-initiated exercise interventions in women ages 40-65 years: The S.W.E.A.T. Study (Sedentary Women Exercise Adherence Trial).

BACKGROUND: In an 18-month exercise intervention in previously sedentary older women (40-65 years), we examined whether an initial 6 months of supervised exercise leads to greater long-term retention and adherence to regular physical activity than an unsupervised home-based program and whether these outcomes are influenced by the exercise intensity. METHODS: Women (N = 126) were recruited from the community and randomly assigned to either center-based or home-based exercise three times/week. The center-based group attended supervised sessions for 6 months, while after 10 initial sessions the home-based group exercised at home. After 6 months both groups were home-based for a further 12 months. Within each arm, subjects were further randomized to exercise at either moderate or vigorous intensity. RESULTS: The center-based group had higher retention than the home-based (97, 94, 81 versus 87, 76, and 61%) at 6, 12, and 18 months, respectively (P < 0.05). At 6 months, adherence was higher in the center-based group (84 versus 63%, P < 0.001) and energy expenditure was higher at 6 (P < 0.05) and 12 (P < 0.01) months. At 18 months, retention was higher with moderate exercise (P < 0.05), while adherence was similar with both intensities. CONCLUSION: An initial 6 months of center-based exercise enhanced retention in both the short and the long term and promoted short-term adherence and energy expenditure. Long-term, moderate exercise retained more subjects, but had little influence on adherence.

Adult↗
PubMed2003

Exercise behaviour change in 40 to 65-year-old women: The SWEAT Study (Sedentary Women Exercise Adherence Trial).

OBJECTIVE: The purpose of this study was to examine the relation between self-reported psychological processes and changes in exercise behaviour in an 18-month longitudinal stage-based intervention trial in 115 initially sedentary women aged 40-65 years. DESIGN: A two-way factorial design was used. METHODS: Participants were assigned randomly to either moderate or vigorous and either home or centre-based exercise. After six months, all participants exercised at home. Participants completed questionnaires at baseline, six, 12 and 18 months which assessed stage of exercise behaviour, self-efficacy, decisional balance and processes of change. RESULTS: 28 patterns of stage change were identified across the 18 months with 6.1% remaining sedentary and 45% demonstrating linear movement from contemplation to action to maintenance to continued maintenance. Two interpretable clusters were identified within both the contemplation (at baseline) and action (at six months) stages. Cluster membership, however, did not influence behaviour change. For participants demonstrating a linear pattern of change, self-efficacy for overcoming barriers and behavioural processes increased from contemplation to action. Self-efficacy for exercise competence increased from contemplation to action but was more pronounced for the vigorous exercise groups. Decisional balance showed a three-way interaction and there was no change for experimental processes. There was no change in any variable from action to maintenance. CONCLUSIONS: The intervention was seen to be effective regardless of location or intensity of exercise. The relevance of substages is questionable in stage-based interventions as women with a profile suggesting less readiness to change or sustain change were just as likely to adopt or maintain exercise.

Adult↗
PubMed2001

Non pharmacologic therapy and lifestyle factors in hypertension.

Lifestyle factors are now recognised to be key determinants of both the rise in blood pressure with ageing and the cardiovascular disease associated with essential hypertension. This paper summarises recent evidence for independent or additive effects of different aspects of diet and behavioural factors on blood pressure levels and some related cardiovascular risk factors. The influence of single nutrients, fats, fibre, protein, antioxidants, caffeine, complex dietary patterns, physical activity, alcohol and smoking will be considered against a background of obesity and psychological factors contributing to blood pressure elevation.

Blood Pressure↗
PubMed2001

Long-term effects of exercise on blood pressure and lipids in healthy women aged 40-65 years: The Sedentary Women Exercise Adherence Trial (SWEAT).

OBJECTIVES: To evaluate the long-term effects of regular moderate or vigorous intensity exercise on blood pressure and blood lipids in previously sedentary older women. DESIGN: Subjects were randomly assigned to either a supervised centre-based (CB) or a minimally supervised home-based (HB) exercise program, initially for 6 months. Within each program, subjects were further randomized to exercise either at moderate (40-55% heart rate reserve, HRres) or vigorous intensity (65-80% HRres). After 6 months, all groups continued a HB moderate or vigorous exercise program for another 12 months. METHODS: Healthy, sedentary women (aged 40-65 years) (n = 126) were recruited from the community. Subjects exercised three times per week for 30 min. They were evaluated at baseline, 6, 12 and 18 months. RESULTS: There was a significant fall of 2.81 mmHg in systolic blood pressure (P = 0.049) and 2.70 mmHg in diastolic blood pressure (P = 0.004) after correction for age and baseline values with moderate exercise, but not with vigorous-intensity exercise. When this analysis was repeated with the change in body mass included, the results were unchanged. After correction for potential confounding factors, there was a significant fall in total cholesterol and low density lipoprotein cholesterol with vigorous but not moderate exercise at 6 months (P < 0.05) but not at 18 months. CONCLUSIONS: In this largely normotensive population of older women, a moderate, but not vigorous exercise program, achieved sustained falls in resting systolic and diastolic blood pressure over 18 months. The study demonstrates that, in older women, moderate intensity exercise is well accepted, sustainable long-term and has the health benefit of reduced blood pressure.

Adult↗
PubMed1999

Oral administration of myelin basic protein is superior to myelin in suppressing established relapsing experimental autoimmune encephalomyelitis.

Oral administration of a myelin component, myelin basic protein (MBP), induces immunological unresponsiveness to CNS Ags and ameliorates murine relapsing experimental autoimmune encephalomyelitis (REAE). However, a recent clinical trial in which multiple sclerosis patients were treated with repeated doses of oral myelin was unsuccessful in reducing disease exacerbations. Therefore, we directly compared the tolerizing capacity of myelin vs MBP during REAE in B10.PL mice. Oral administration of high doses of myelin, either before disease induction or during REAE, did not provide protection from disease or decrease in vitro T cell responses. In contrast, repeated oral administration of high doses of MBP suppressed established disease and MBP-specific T cell proliferation and cytokine responses. The frequency of IL-2-, IFN-gamma-, and IL-5-secreting MBP-specific T cells declined with MBP feeding, implicating anergy and/or deletion as the mechanism(s) of oral tolerance after high Ag doses. We have previously shown that the dosage and timing of Ag administration are critical parameters in oral tolerance induction. Studies presented here demonstrate that Ag homogeneity is also important, i.e., homogeneous Ag (MBP) is more effective at inducing oral tolerance than heterogeneous Ag (myelin).

Administration, Oral↗
PubMed1999

Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus.

In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.

Acute Disease↗
PubMed1999

Paediatric liver transplantation: indications, timing and medical complications.

Newer surgical techniques and immunosuppressive therapies have resulted in paediatric liver transplantation being available for most children with end-stage liver disease and has resulted in a greater than 80% 5-year survival rate. The most common indications for paediatric liver transplantation are biliary atresia (43%), metabolic disease (13%) and acute hepatic necrosis (11%). For approximately 75% of children with acute hepatic failure, the cause is unknown. Timing of liver transplantation not only affects survival rate, but may influence neurodevelopmental outcome. Fortunately, numerous types of donors, such as reduced-sized, living related or unrelated and blood-type mismatched, have reduced the mortality of children who are waiting for liver transplantation. However, the mortality and morbidity before and after liver transplantation remain high for children who have fulminant hepatic failure or are less than 5 months of age at the time of transplantation. The principle medical complications after liver transplantation are rejection and infection. Although use of newer immunosuppressive regimens has reduced the rate of rejection, Epstein-Barr virus infection with associated lymphoproliferative disorder remains the principle cause for morbidity and mortality after the initial 3 months post-liver transplant.

Adolescent↗
PubMed1998

Factors associated with delay in giving thrombolytic therapy after arrival at hospital.

OBJECTIVE: To identify factors associated with delay in administration of thrombolytic therapy for acute myocardial infarction. DESIGN: Retrospective case note review of a six-month period in 1995. Data were obtained on age, sex, hospital arrival time, triage priority, assessment process in the emergency department, grade of emergency doctor, patient history, timing of and findings on electrocardiogram (ECG), type of infarct, timing and site of administration of thrombolytic therapy, and type of thrombolysis given. SETTING: Tertiary referral hospital in Newcastle, New South Wales. PARTICIPANTS: Eighty-five patients given thrombolytic therapy for acute myocardial infarction. OUTCOME MEASURE: Time between hospital arrival and initiation of thrombolytic therapy. RESULTS: The median time from hospital arrival to administration of thrombolytic therapy was 80 minutes (interquartile range [IR], 50-133). Only 26% of patients were triaged to Priority 1 or 2 (to be seen by a doctor within 10 minutes). Patients initially assessed by a specialist emergency physician received thrombolytic therapy a median of 38 (IR, 33-50) minutes after hospital arrival, compared with 65 (IR, 50-107) minutes if initially assessed by a medical registrar, and 148 (IR, 89-185) and 160 (IR, 95-163) minutes, respectively, if initially assessed by an intern or a resident medical officer (P < 0.001). Factors associated with increased delay in receiving thrombolytic therapy (after adjustment for possible confounders) were low triage priority, initial assessment by a junior doctor, atypical presenting history of myocardial infarction, and lesser degrees of ST-segment elevation on the presenting ECG (all P < or = 0.01). CONCLUSIONS: Delay in administration of thrombolytic therapy in hospital results from a combination of hospital and patient factors. Changes in emergency department protocol may reduce these delays in some patients.

Aged↗
PubMed1998

Oral tolerance as therapy for experimental autoimmune encephalomyelitis and multiple sclerosis: demonstration of T cell anergy.

Experimental autoimmune encephalomyelitis (EAE) is an important model for developing therapies for multiple sclerosis (MS). The oral administration of the central nervous system antigen, myelin basic protein (MBP), to Lewis rats and susceptible mouse strains prior to MBP immunization prevents the induction of EAE. Clinical trials administering myelin orally to MS patients have met with only partial success, and thus require that oral tolerance be further studied to improve this treatment strategy. Clonal anergy, clonal deletion, immune deviation from Th1 to Th2 T cell subsets, and active suppression by TGF-beta-secreting T cells have all been implicated as possible mechanisms in oral tolerance. Which mechanism predominates depends on antigen dosage, frequency of feeding, and timing of antigen administration. In this study, we have characterized T cells derived from MBP-fed rats and determined the level of their unresponsiveness. Myelin basic protein-specific T cells are indeed present although in reduced numbers in lymphoid tissue of orally tolerized animals. Following several cell divisions in the presence of IL-2, these MBP-specific T cells undergo a dramatic reversal of unresponsiveness, proliferate in response to MBP and are capable of transferring EAE. These results support clonal anergy as an important mechanism for oral tolerance. Recent developments in clinical trials of oral tolerance are described.

Administration, Oral↗
PubMed1998

Liver transplantation at Stanford University Medical Center.

Because of the unique demographics of our patient population, we have had the opportunity to dedicate further studies of the management of hepatitis B and hepatitis C. We have experienced a very low HBV recurrence rate with the use of HBIG in patients transplanted for hepatitis B. Investigations, including the use of new antiviral agents, and the development of approaches to minimize or abrogate disease recurrence such as lower levels of immunosuppression are ongoing. Using a standardized approach to the proper evaluation and selection of patients for liver transplantation with alcoholic liver disease or other liver diseases with coexistent alcohol abuse, we report favorable long-term results in these patients. We have reviewed our results and our approach to the management of EBV and posttransplant lymphoproliferative disorder. There is a firm commitment in our laboratories and outpatient clinics to the investigation of disease prevention, reliable detection and screening methods, and treatment modalities for EBV-related disease. We have addressed specific technical considerations to pediatric liver transplant and have discussed unique aspects of postoperative management in these patients. One-third of the transplants performed at Stanford are in children, 42% of whom are less than one year old. Results with our pediatric transplant recipients compare favorably with those of our adult recipients with patient and graft survival rates approaching 90% at one year and exceeding 80% at 46 months for both groups. As a response to the limited organ supply, we have extended our criteria for suitable donors. Most notably, we have utilized older donors and grafts with significant microsteatosis and have observed good results with these grafts as long as ischemia time is minimized. We have also successfully used reduced size grafts for our pediatric patients with good results and are continuing to expand the use of living-related partial grafts and split allografts.

Adolescent↗
PubMed1997

Cholic acid synthesis is reduced in pediatric liver recipients during graft dysfunction due to ischemic injury and allograft rejection.

BACKGROUND: Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation. METHODS: We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection. RESULTS: There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids. CONCLUSIONS: Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.

Adolescent↗
PubMed1997

Factors affecting survival after orthotopic liver transplantation in infants.

The technical and medical management of small infants requiring orthotopic liver transplantation remains a challenge. The present study examined 117 orthotopic liver transplantations performed in 101 infants from <1 to 23 months of age between March 1988 and February 1995 to determine factors that influence patient and graft outcome. Factors analyzed included etiology of liver disease, recipient and donor age and weight, United Network for Organ Sharing (UNOS) status, retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts, vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic failure, and the development of Epstein-Barr virus-associated LPD were each associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11 (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9 hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%), all less than 1 year of age, and was associated with significantly poorer 1-year (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT, P<0.01). One-year graft survival rates for FS grafts in recipients <12 months versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05). Recipients <5 months of age had the worst survival rates: 1-year and 5-year patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus 82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age 12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival rates include recipient age <5 months, recipient age <12 months who received FS grafts, development of VT and donor weight <6 kg. There was a trend for UNOS status 1, fulminant hepatic failure, and presence of LPD to be associated with reduced survival rates.

Aging↗
PubMed1997

Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: a case report.

Since the first successful report regarding the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) as an alternative to surgical decompression of portal hypertension, this method has been used extensively as a temporizing measure in controlling refractory variceal bleeding before liver transplantation in adults with cirrhosis. There are few reports of TIPS in pediatric patients because variceal bleeding in most of these patients can often be managed conservatively without invasive intervention. Recently, successful use of TIPS to treat complications of portal hypertension has been described in two children ages 10 and 13. To our knowledge, there are no reports of TIPS used in infants under the age of 1 year. The authors report a case in which TIPS was used to successfully control variceal bleeding in a 10-month-old infant before consideration for hepatic transplantation.

Blood Transfusion↗
PubMed1997

Neurodevelopmental outcome of young children with extrahepatic biliary atresia 1 year after liver transplantation.

STUDY DESIGN: Forty children < 2 years of age receiving extrahepatic liver transplantation were tested with the Bayley Scales of Infant Development before transplantation and again at 3 and 12 months after transplantation. Neurodevelopmental status 1 year after transplantation was organized by a descriptive statistic of normal, suspect, or delayed. Disease and transplantation variables were investigated for association with delayed neurodevelopmental outcome. RESULTS: Before transplantation mental development was in the low-average range (92 +/- 13.2) with psychomotor development 1 SD below the norm (82.5 +/- 13). Three months after transplantation both mental (80.1 +/- 12.6) and psychomotor (69 +/- 16.1) scores dropped 1 SD, but 1 year after transplantation mental and psychomotor scores recovered to the pretransplantation level of functioning. One year after transplantation 35% of the study group was diagnosed as developmentally delayed. Delayed development was associated with decreased weight (p < 0.04), low albumin (p < 0.02), length of hospital stay (p < 0.04), and age at transplantation (p < 0.05). CONCLUSION: Young children undergoing liver transplantation are at risk for developmental delay. Aggressive nutritional support before transplantation and timing of transplantation before malnutrition develops may reduce developmental delays.

Age Factors↗