Relationship between neurocognitive functioning and medication management ability over the first 6 months following allogeneic stem cell transplantation.

Although neurocognitive impairment has been established as a major issue among cancer survivors, the real-world consequences of this impairment are unclear. This study investigated the relationship between neurocognitive functioning and medication management ability over time among 58 patients treated with allogeneic hematopoietic stem cell transplantation (HCT). Participants completed a neuropsychological test battery and a simulated medication management task at three time points: pre-transplant (T0), Day 100 (T1) and 6 months post transplant (T2). Neurocognitively impaired participants performed worse on the medication management task than neurocognitively normal participants at each time point, and were more likely to score in the impaired range of medication management ability post transplant (72% vs 20%, P<0.001 at T1; 67% vs 23%, P=0.013 at T2). In multivariate analyses, worse performance in executive functioning/working memory consistently predicted impaired medication management ability, even when controlling for sociodemographic and clinical confounders (odds ratio=0.89, 95% confidence interval (0.80, 0.98), P=0.023). Lower physical symptom distress also predicted impaired medication management ability, but this effect decreased over time. Self-reported cognitive problems were not correlated with medication management ability at any time point. Findings suggest that poor neurocognitive functioning, particularly in the domain of executive functioning/working memory, is associated with worse medication management ability within the first 6 months after allogeneic HCT.

Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2.

For AML, older age, advanced disease and increased hematopoietic cell transplant comorbidity index (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). This single-center retrospective study investigated the influence of pre-transplant characteristics on outcomes of 387 patients undergoing allogeneic HCT for AML in CR1 and CR2. The multivariable analysis model for overall survival (OS) included age (hazard ratio (HR)=2.24 for ages 31-64 years and HR=3.23 for age ⩾65 years compared with age ⩽30 years, P=0.003), remission status (HR=1.49 for CR2 compared with CR1, P=0.005) and HCT-CI score (HR=1.47 for ⩾3 compared with <3, P=0.005). Transplant year was significantly associated with OS (P=0.001) but this did not influence the model. A weighted score was developed with age ⩽30, CR1 and HCT-CI score <3 receiving 0 points each, and CR2 and HCT-CI score ⩾3 receiving 1 point each. Ages 31-64 received 2 points, age ⩾65 received 3 points. Scores were grouped as follows: scores 0-1 (low risk, n=36), score 2 (intermediate-low risk, n=147), score 3 (intermediate-high risk, n=141) and scores 4-5 (high risk, n=63) with 3-year OS of 71%, 55%, 42% and 29% for scores 0-1, 2, 3 and 4-5, respectively (P<0.0001). The score predicted nonrelapse mortality (P=0.03) but not cumulative incidence of relapse (P=0.18). This model should be validated for the pre-HCT assessment of AML patients in CR1 and CR2.

Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission.

Secondary AML (sAML) has a poor prognosis with conventional chemotherapy alone. Allogeneic hematopoietic cell transplantation (HCT) is beneficial for high-risk AML. Data comparing outcomes of transplants for patients with de novo and sAML are limited. We compared outcomes of patients transplanted for de novo and sAML in first complete remission and investigated the effect of age, HCT comorbidity index (HCT-CI) and karyotype in both groups. A total of 264 patients with de novo (n=180) and sAML (n=84) underwent allogeneic HCT between 1999 and 2013. Median age at transplant was 51 years (range 18-71), median follow-up of survivors was 77 months. Evaluation of all patients demonstrated no significant difference between de novo and sAML for overall survival (P=0.18), leukemia-free survival (P=0.17), cumulative incidence of relapse (P=0.51) and non-relapse mortality (P=0.42). Multivariable and propensity score analyses confirmed the comparable outcomes between de novo and sAML post transplant. Although sAML demonstrates outcomes inferior to de novo AML treated with chemotherapy alone, outcomes following allogeneic HCT are comparable between the two groups.

Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR.

Allo-SCT is potentially curative for patients with AML. Patients transplanted in CR2 tend to experience inferior survival compared with those in CR1. We retrospectively investigated the impact of pretransplant variables on the outcome of patients transplanted with AML in CR2. Ninety-four patients with AML in CR2 received a transplant between 1999 and 2011 with myeloablative (MA, n=65) or reduced-intensity conditioning regimens (RIC, n=29). Variables investigated included cytogenetic risk at diagnosis (SWOG), hematopoietic cell transplantation-specific comorbidity index (HCT-CI), CMV status, duration of CR1 and age. Median age of all patients was 47 years (range 18-70). Multivariable analysis for OS identified three prognostically significant categories: a favorable risk group included patients with duration of CR1 ≥6 months, age <55 years and HCT-CI score 0-3, an intermediate risk group with duration of CR1 ≥6 months, age <55 years and HCT-CI score 4-5 and a high-risk group with duration of CR1 <6 months or age ≥55 years (P=0.0001) with 5-year survivals of 53%, 31% and 6%, respectively. Acute and chronic GVHD did not influence this risk stratification. The stated risk factors discriminate patients with different OS and may assist in decision making for allo-SCT.

Unemployment rates, single parent density, and indices of child poverty: their relationship to different categories of child abuse and neglect.

OBJECTIVE: There were two main research questions: First, is there a relationship between rates of child physical abuse, child sexual abuse and child neglect and levels of female and male unemployment, single-parent density and child poverty in the immediately local area; and second, is this relationship different for different categories of abuse and neglect and different categories of deprivation? METHOD: Using archival data--registered cases of abuse and neglect and official data on child population, social worker ratio, unemployment rates, single-parent density, means-tested clothing grants and free school meals for children--a multiple correlational analysis was carried out of the 5,551 referrals and 1,450 registered cases of abuse and neglect in Glasgow, Scotland for the years 1991 through to 1993. RESULTS: Substantial correlations were found with all indices of deprivation but particularly physical abuse with rates of male unemployment. Lower and more variable correlations were found with female unemployment rates. Sexual abuse and neglect rates showed a less consistent relationship with the indices of deprivation. In general male unemployment rates alone accounted for two-thirds of the variance in total abuse and neglect rates, other factors adding little or nothing to this. CONCLUSIONS: The results demonstrate the importance of selecting small and relatively homogeneous areas for this kind of analysis to achieve ecological validity. Male unemployment rates at this level allow for the ranking of areas in terms of priority need.

Sheep-acquired severe Chlamydia psittaci infection in pregnancy.

There have been five confirmed cases of severe Chlamydia psittaci infection during pregnancy, three having been treated in Edinburgh, Scotland. The most recent case is presented and previous experience is reviewed. The illness usually causes thrombocytopenia with disseminated intravascular coagulation, renal failure and hepatic dysfunction during the late second and early third trimester. The outcome for the fetus is usually fatal and the infection only resolves after delivery or abortion. The main hope is for education to prevent infection occurring in susceptible populations.

The kallikrein-kinin and renin-angiotensin systems in nephrotic syndrome.

We previously found that virtually all patients with nephrotic syndrome (NS) excrete supranormal amounts of urinary kallikrein; it is known that activity of the renin-angiotensin system (RAS) is increased in some such patients. We therefore studied the relationship between urinary kallikrein excretion (UKa) and plasma renin activity (PRA) in 16 patients with NS. Compared with healthy controls, PRA was normal in 8 subjects and elevated in 8; UKa was elevated in the high-renin group (40.4 +/- 5.2 nkat/24 h, normals 12.0 +/- 1.1). UKa was also elevated in the normal renin group (25.7 +/- 2.4 nkat/24 h) but to a significantly lesser degree. Significant activity in plasma against a specific substrate of glandular and renal kallikreins was observed in 8 of 10 patients with NS. Such activity was not found in plasma of 17 patients with glomerulonephritis without NS, or in 10 healthy controls. The results are in keeping with previous suggestions of a functional link between the renal kallikrein-kinin system (KKS) and the RAS, but indicate that the renal KKS is activated in NS, in some cases independently of the RAS. It is possible that renal kallikrein reaches the systemic circulation in some patients with NS.

Urinary kallikrein excretion in chronic renal failure: relationship to blood pressure and the acute effect of captopril.

Previous studies of the renal kallikrein-kinin system in chronic renal failure (CRF) have given conflicting results. We have assessed activity of this vasoactive hormone system in CRF and investigated a possible relationship to hypertension in patients with CRF: 24-hour urinary kallikrein excretion (UKa) was measured in 22 patients with CRF (9 normotensive and 13 hypertensive) and 11 healthy controls. Age, sex, urine volume, and urinary sodium excretion were similar in each group. Compared with controls, UKa was reduced in both normotensive and hypertensive patients with CRF, with no difference between CRF groups. The reduction in UKa in CRF was less than the reduction in glomerular filtration rate (GFR), as assessed by endogenous creatinine clearance (CCr). When UKa was divided by CCr, UKa/mL CCr was therefore increased, to a similar extent, in both normotensive and hypertensive patients with CRF. This suggests that release of renal kallikrein from functioning nephrons is increased in CRF. The results do not support a role for deficient kallikrein release in the genesis of hypertension in CRF, as previously suggested; however, these abnormalities could be relevant to other aspects of renal function in CRF. The converting-enzyme inhibitor, captopril, was given to 5 patients with CRF, hypertension, and low UKa. Introduction of captopril was followed by a further reduction in UKa in all subjects. Captopril is known to inhibit kininase II, the principal enzyme involved in degradation of kinins; this potentiating effect may be counteracted by a reduction in renal kallikrein release and hence in kinin generation.

Urinary kallikrein and systemic prostacyclin synthesis during sodium chloride infusion in normal man.

An intravenous infusion of 3 litres of sodium chloride solution (saline: 150 mmol/l) was given over 1 h to normal subjects. During and immediately after the infusion, renal plasma flow increased in the majority of subjects, but the rise was not statistically significant. Significant increases in urine flow, sodium excretion, urinary kallikrein excretion and urinary excretion of dinor-6-keto prostaglandin (PG) F1 alpha, a measure of systemic PGI2 synthesis, were noted. Plasma renin activity and plasma protein concentration were significantly lowered by the infusion. At 2 h after the end of the infusion, although urine flow fell significantly, sodium excretion had not decreased. The reduction in plasma renin activity and plasma proteins persisted, and excretion of kallikrein and the PGI2 metabolite returned to control values. Overall, urinary kallikrein excretion correlated significantly with urine flow and with sodium excretion. Peak kallikrein excretion occurred in the second 30 min of the infusion, and preceded maximal urine flow and sodium excretion. The results suggest that increased systemic synthesis of PGI2 occurs in response to an acute infusion of sodium chloride, and may be an adaptive response of the vasculature to volume expansion. They support a role for the renal kallikrein-kinin system in the early diuretic and natriuretic response to saline infusion; the reduction in plasma renin activity and plasma protein concentration may be involved in both the early response and the persistent natriuresis 2 h after the infusion.

Hypocalcaemic cataract as a presenting symptom of renal insufficiency.

A young man of 17 years presented with bilateral reduced vision because of cataracts. Investigations showed a low level of serum calcium along with other evidence of renal failure. The cataracts were mainly in the posterior pole (cupulliform); faint peripheral cortical opacities were also present--in the form of about a dozen half-loops straddling the equator and extending about half way towards the axial centre of the lens.

Thyroid status in patients with chronic renal failure.

Serum thyroid hormone concentrations have been measured in 21 patients with chronic renal failure, treated conservatively and compared with values from 19 control subjects. Many patients had serum total T3 and T4 concentrations below the reference ranges. The concentrations of free T4 and free T3 and the free thyroxine index were significantly lower in patients with abnormal total concentrations of the thyroid hormones than in the controls. Both the free and the total concentrations of T4 correlated inversely with the degree of renal failure. The concentration of thyroxine binding globulin (TBG), fell within the reference range in each of the patients, but was significantly lower in the patient group when compared with the controls. These TBG concentrations, however, were not sufficiently decreased to explain the low total thyroid hormone concentrations found in the patients. The affinity of TBG for T4 and T3 in the patient and control groups was not significantly different. The TSH response to TRH was diminished in many of the patients, but the measurement of other pituitary hormones indicated that pituitary function was normal in these patients. The possible mechanisms responsible for the changes observed in thyroid and pituitary hormones are discussed.

Disseminated aspergillosis occurring in patients with respiratory, renal, and hepatic failure.

Respiratory, renal, and hepatic insufficiency developed in five patients who had been admitted to hospital for a variety of reasons. Although in four cases Aspergillus had been isolated from tracheal secretions before death, the significance of this finding was not fully appreciated, and in all five the diagnosis of aspergillosis was made at necropsy. Since treatment has to be started early if it is to be effective, patients with any combination of respiratory, renal, and hepatic failure should have their tracheal secretions examined daily. If Aspergillus is cultured, and hyphae are present in a fresh smear, and the patient has features of a generalised infection without an obvious site of infection, treatment for aspergillosis should be considered.

Role of prostaglandins in mediating excretion by the kidney of an intravenous infusion of sodium chloride in normal human subjects.

1. Normal male subjects were given a rapid infusion of 3 litres of sodium chloride solution (150 mmol/l) with or without pretreatment with indomethacin. 2. There was marked individual variability in the rate at which the infused sodium chloride solution was subsequently excreted which was not related to the urinary sodium excretion in the previous 24 h. 3. There was no relationship between urinary prostaglandin E excretion during the 24 h preceding the sodium chloride infusion and the rate at which different individuals subsequently excreted sodium and water. 4. Renal plasma flow was significantly higher during the sodium chloride infusion than in the post-infusion recovery period, both with and without pretreatment with indomethacin, although it was significantly lower during each period in subjects pretreated with indomethacin. 5. Urinary prostaglandin E excretion was significantly decreased after the infusion of sodium chloride solution. 6. Indomethacin slightly decreased the rate of excretion of sodium and water. 7. Prostaglandins have a role in, but are not the main determinants of, the excretion of an intravenous infusion of sodium chloride. 8. The results do not support the suggestion that prostaglandin E produced within the kidney, as indicated by urinary prostaglandin E excretion, exerts a natriuretic action.