Validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients.

AIM: This study assessed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients. METHODS: We recruited 223 non-cancer patients receiving palliative care and their healthcare providers (222) across two home care facilities and two hospitals for a cross-sectional study. We assessed the construct validity and known-group validity of the Integrated Palliative Care Outcome Scale. The weighted kappa and interclass correlation coefficients were assessed to ascertain reliability. RESULTS: The scale scores were significantly higher for the 'non-stable' group (worsening condition group) measured in the palliative care phase than for the 'stable' group (P < 0.001). Regarding validity, Spearman's correlations between similar items on the Integrated Palliative Care Outcome Scale and Edmonton Symptom Assessment System ranged from 0.61 to 0.94. Regarding reliability, the weighted kappa coefficients ranged from 0.53 to 0.81 for patients and from 0.58 to 0.90 for healthcare providers. For inter-rater reliability between patients and healthcare providers, the weighted kappa coefficients for each item ranged from 0.03 to 0.42. CONCLUSION: This study confirmed the validity and reliability of the Integrated Palliative Care Outcome Scale for non-cancer patients requiring palliative care. However, the inter-rater reliability indicates poor agreement between the assessments of patients and healthcare providers. This highlights the discrepancies between both their assessments and the importance of the patient's assessment. Geriatr Gerontol Int 2023; 23: 517-523.

Highly Diastereoselective Synthesis of 2-(1-N-Boc-aminoalkyl)thiazole-5-carboxylates by Reduction of tert-Butylsulfinyl Ketimines.

Positional isomers of naturally occurring peptide subunits were synthesized via highly diastereoselective reduction of tert-butylsulfinyl ketimines as a key reaction. While NaBH4 reduction of ketimines derived from 2-thiazolyl ketones afforded the (RS,R)-isomer with moderate diastereoselectivity, L-Selectride® reduction afforded the (RS,S)-isomer as the sole product. In contrast, ketimines derived from tert-butyl 2-thiazolyl ketone afforded the (RS,R)-isomer with low diastereoselectivity by both NaBH4 and L-Selectride® reduction. Stereochemistry of the reaction was discussed based on calculation of the conformational energies for ketimines.

Metabolic responses during hemodialysis determined by quantitative (1)H NMR spectroscopy.

A large proportion of patients with end-stage renal disease have lifelong hemodialysis (HD) treatment. HD rapidly and indiscriminately removes necessary small metabolites together with uremic toxins from plasma into dialysate. To investigate metabolic responses to HD, we determined the levels of metabolites through time-course monitoring of (1)H NMR spectroscopy of dialysate during HD. The dialysate sample is stable for analysis because it contains only small metabolites without proteins. It was collected non-invasively from 9 HD patients with chronic glomerular nephropathy, at 6 time points during 4h of HD in 5 sessions. Creatinine, alanine, lactate, pyruvate and valine were simultaneously quantified on a one-dimensional single-pulse spectrum with a single standard compound. The concentration of creatinine exhibited monotonous decay with time, while that of valine decreased slowly and then maintained its levels throughout an HD. Lactate, alanine and pyruvate increased at 2-3h after the initiation of HD. They exhibited remarkable responses to HD with production from the body. The time-course of change in the 4 metabolites of lactate, pyruvate, alanine, and valine had reproducible behavior unique to each patient during the HD. This finding may be applied to distinguish metabolic status in HD patients.

Sex differences in the prevalence, progression, and improvement of chronic kidney disease.

BACKGROUND/AIMS: We examined sex differences in prevalence, progression, and improvement in early-stage chronic kidney disease (CKD). METHODS: We analyzed data from 533 participants who took 4 consecutive annual CKD detection tests. RESULTS: Urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and hemoglobin (Hb) at baseline in men with and without CKD and in women with and without CKD were 8.3±6.1, 149.2±310.4, 10.2±5.8, and 96.7±246.8 mg/g Cr; 83.4±14.7, 63.8±18.8, 79.9±13.0, and 69.4±20.0 mL/min/1.73 m2; and 14.8±1.2, 14.3±1.4, 13.0±1.0, and 13.0±1.2 mg/dL, respectively. ACR levels decreased significantly over time in men and women with CKD and they increased significantly over time in men and women without CKD. eGFR levels in men and women with CKD did not significantly change over time, but they decreased significantly over time in men and women without CKD. CKD prevalence and progression rate were not significantly different between sexes. Among the CKD participants, significantly more women had a "cured" status at 3 years (39.1% vs. 19.4%, P<0.01). Most whose eGFR increased to >60 mL/min/1.73 m2 at 3 years had values just below those at baseline. Regression analysis showed that change in eGFR correlated significantly with ACR in men with CKD (change in eGFR = -1.707+0.022×ACR, P<0.001, r2=0.201) and with Hb and ACR in women with CKD (change in eGFR = 48.870-3.803×Hb + 0.018×ACR, P<0.05, r2=0.134). CONCLUSIONS: These results suggest that the slight decrease of Hb within a normal range and mild anemia can be managed in women with early-stage CKD. The key baseline for eGFR is 60 mL/min/1.73 m2.

¹H NMR spectroscopic quantification of plasma metabolites in dialysate during hemodialysis.

We used ¹H nuclear magnetic resonance (NMR) spectroscopy to assess metabolic responses in patients undergoing hemodialysis (HD). We collected 71 samples of plasma and dialysate from 10 patients before, during, and after HD. We used the dialysate as a possible substitute for blood plasma to quantify small metabolites by ¹H NMR. We confirmed TSP (sodium 3-(trimethylsilyl) propionate 2, 2, 3, 3-d4) as a reference of NMR intensity in dialysate. We examined TSP sensitivities in various dialysate spectra and the correlation between signal intensities and added quantities of TSP. We used integrations of signal areas on ¹H NMR spectra of plasma and dialysate to quantify concentrations of creatinine, lactate, alanine, and valine and calculate their ratios between plasma and dialysate. The ratios of metabolites in plasma to dialysate were 3.2±0.4 (creatinine), 3.6±0.5 (valine), 3.8±0.7 (alanine), and 4.0±0.8 (lactate) mM (mean±standard deviation [SD]). The broader distributions of ratios in levels of lactate and alanine suggested their de novo production during the HD session. Estimation of blood metabolite levels using dialysate is useful for quantitative analysis of metabolic status in blood during HD.

Three-year follow-up of lanthanum carbonate therapy in hemodialysis patients.

For 3 years following the start of lanthanum carbonate therapy, effects on other pharmaceutical treatment with sevelamer hydrochloride (SH), calcium carbonate (CC), and vitamin D, and those on clinical condition were examined. Dialysis patients with hyperphosphatemia (89 cases; average age 55.2 years; dialysis history of 10 years; 50 male and 39 female), who agreed to start lanthanum carbonate (LC) administration, were observed for a mean period of 32.6 ± 6.2 months. Mean daily dosages of CC and SH before starting LC were 2.68 g and 0.73 g; mean daily dosage amounts of LC, CC, and SH at the time of final evaluation were 0.87 g, 2.30 g, and 0.99 g, respectively. After the application of LC, serum phosphate as well as serum calcium controls were significantly improved, and the amounts of active vitamin D agents applied was significantly increased. In conclusion, LC is useful in managing serum phosphorus levels (P levels), and little incidence of hypercalcemia suggests favorable concomitant use with active vitamin D agents in LC therapy.

Blood pressure and sympathetic nerve tone relation during hemodialysis may reflect cardiovascular dysfunction.

BACKGROUND: The blood pressure response to the rapid removal of fluid during hemodialysis is complex and the pathophysiological mechanisms underlying intradialytic hypotension are not clear and sometimes these mechanisms render dialysis difficult to continue. PURPOSE: We analyzed the changes in blood pressure and sympathetic nerve tone and attempted to clarify whether the dynamic pattern of this relationship reflects cardiovascular dysfunction. METHODS: The dynamic pattern of sympathetic nerve activity throughout dialysis was analyzed by frequency analysis of RR intervals recorded by 24 hours Holter electrocardiography in 64 patients and 3 minutes ECG every 15 minutes during dialysis in 121 stable end-stage renal failure patients who underwent maintenance hemodialysis. Blood pressure and fluid volume removed was measured every 15-30 minutes during dialysis and the average value of the ratio of low to high frequency components (LF/HF) was calculated as an index of sympathetic nerve tone. The relationship between removed fluid volume, systolic blood pressure (Bp) and LF/HF was analyzed. RESULTS: The patients were classified into 3 groups based on the correlation between the LF/HF and Bp as follows: positive (52 cases), inverse (54 cases), and not significant (NS; 61 cases). Eighteen patients who showed multiple arrhythmias, atrial fibrillation and other artifacts or noises were eliminated as they were inadequate for frequency analysis of RR intervals. The positive group was characterized by a hypotension-resistant response with a low LF/HF, whereas the inverse group was characterized by a hypotension-prone response with high LF/HF. These results suggest that cardiovascular dysfunction is responsible for the inverse correlation. CONCLUSION: Analysis of the relationship between sympathetic nerve tone and Bp is effective in predicting the existing of cardiovascular dysfunction.

Attempt of quantitative analysis of visual evaluation for (123)I-BMIPP myocardial scintigraphy images.

We developed a new technique to quantitatively analyze visual evaluation single photon emission computed tomography (SPECT). Short axis tomograms and color scales were computer scanned. The scales were divided into 25 parts; numbers of each hue pixel were scored 0-100%. Short-axis images were divided into eight equal partitions, numbers of hue pixels distributed in each partition were scored, and total scores were obtained. Each partition's radio-isotope (RI) accumulation index was calculated as partition score/highest score. For method validation, scintigrams from each left ventricular phantom part were divided into eight partitions and filled with (123)I-BMPP (10-100%). The error between theoretical and calculated concentrations was within 20% in the concentration range of ≥50%, suggesting a good correlation and indicating the method's validity.

Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study.

PURPOSE: Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis. PATIENTS AND METHODS: The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group. RESULT: During the 12-months' observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70-2.17]; CKD4, 2.73 (1.55-4.83); and CKD5, 4.66 (2.63-8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09-6.04); DN, 12.21 (3.90-38.20); and ON, 4.14 (1.93-8.89). CONCLUSION: Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.

Quantification of molecules in (1)H-NMR metabolomics with formate as a concentration standard.

Quantitative analysis of metabolites is important in (1)H-nuclear magnetic resonance (NMR)-based metabolomics of plasma. Human plasma contains a high density of proteins which heavily adsorb the commonly-used standard compound of sodium 3-(trimethylsilyl) propionate 2, 2, 3, 3-d(4) (TSP). We have evaluated calcium formate as an alternative standard in 1D single-pulse (1)H-NMR spectra to quantify plasma metabolites. Formate did not interact with either plasma metabolites or proteins under adequate conditions. Linear relations between the signal intensities and the added formate have been demonstrated in (1)H spectra. The quantifications of glucose and creatinine by this method have shown good accordance with biochemical analysis. Calcium formate is applicable as a concentration standard to NMR metabolomics of plasma.

Pattern recognition analysis for 1H NMR spectra of plasma from hemodialysis patients.

1H NMR spectroscopic and pattern recognition-based methods (NMR-PR) were applied to the metabolic profiling studies on hemodialysis (HD). Plasma samples were collected from 37 patients before and after HD and measured by 600 MHz NMR spectroscopy. Each spectrum was data-processed and subjected to principal component analysis for pattern recognition. Spectral patterns of plasma between pre- and post-dialyses were clearly discriminated, together with significant fluctuations in the levels of creatinine, trimethylamine-N-oxide, glucose, lactate, and acetate, which were quantitated. We have first observed the significant elevation of lactate levels in post-dialysis plasma. The present study has demonstrated the high feasibility of NMR-PR method for monitoring the dialysis condition and comprehensive profiling of the change of low-molecular-weight metabolites in HD.

[Hypertension and metabolic syndrome/lifestyle diseases].

Hypertension is caused by metabolic syndrome. The primary cause of hypertension, however, is excess salt intake and an impaired renal salt excretory mechanism of the tubuloglomerular feedback mechanism involved in macula densa. Salt-losing nephropathy such as Gitelman's syndrome (which is caused by loss of function mutation in the tyhiazide-sensitive Na-Cl transporter, NCCT gene) is lacking in hypertension and has fewer cardiovascular complications despite the presence of the stimulated rennin-angiotensin-aldosterone system. It has been reported that an NCCT gene mutation is closely associated with diabetic nephropathy, suggesting an important role of NaCl metabolism in diabetic nephropathy. Loss of function of peroxisome proliferator-activated receptor(PPAR) -gamma(one of the key molecules of insulin resistance) has been shown to lead to obesity, diabetes and hypertension, suggesting a common basic background of such diseases. High insulin levels observed in insulin resistance would stimulate salt reabsorption in renal tubules, which may result in high blood pressure. Adipocytokines such as adiponectin, leptin and angiotensinogen may play some roles in metabolic syndrome. Taken together, good understanding of salt intake and its related factors in renal salt metabolism involved in metabolic syndrome will suppress further progression of atherosclerotic changes including chronic kidney disease.

Effects of monotherapy of temocapril or candesartan with dose increments or combination therapy with both drugs on the suppression of diabetic nephropathy.

We examined the effects of increasing the recommended initial doses of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), or of switching to combination therapy with both drugs, on diabetic nephropathy. Hypertensive type 2 diabetic patients with urinary albumin excretion (ACR) between 100 and 300 mg/g creatinine (Cre) were assigned to the following five groups in which an antihypertensive drug was administered at a recommended initial dose for 48 weeks, and then either the dose was doubled or an additional drugs was added to regimen for the following 48 weeks: N, nifedipine-CR (N) 20 mg/day (initial dose); T, ACEI temocapril (T) 2 mg/day; C, ARB candesartan (C) 4 mg/day; T+C, T first and then addition of C; C+T, C first and then addition of C. ACR decreased in the T (n=34), C (n=40), T+C (n=37) and C+T (n=35) groups, but not in the N group (n=18). However, the anti-proteinuric effect was less in the T than in the C, T+C or C+T groups, while no differences existed among the latter three. In each group, there were significant linear relationships between attained BP and ACR; however, the regression lines were shifted toward lower ACR level in the renin-angiotensin system-inhibition groups compared with the N group. These results indicate that an ACEI and/or ARB is superior to a CCB in retarding diabetic nephropathy, while the combination of low doses of ACEI and ARB has effects similar to those of high-dose ARB. Even among patients treated with an ACEI and/or ARB, lowering BP is important.

Detection of bacteria associated with harmful algal blooms from coastal and microcosm environments using electronic microarrays.

With the global expansion of harmful algal blooms (HABs), several measures, including molecular approaches, have been undertaken to monitor its occurrence. Many reports have indicated the significant roles of bacteria in controlling algal bloom dynamics. Attempts have been made to utilize the bacteria/harmful algae relationship in HAB monitoring. In this study, bacterial assemblages monitored during coastal HABs and bacterial communities in induced microcosm blooms were investigated. Samples were analysed using denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA gene. DGGE bands with peculiar patterns before, during, and after algal blooms were isolated and identified. Probes for six ribotypes representing organisms associated with Chatonella spp., Heterocapsa circularisquama, or Heterosigma akashiwo were used for analysis on NanoChip electronic microarray. In addition, a new approach using cultured bacteria species was developed to detect longer (533 bp) polymerase chain reaction-amplified products on the electronic microarray. The use of fluorescently labelled primers allowed the detection of individual species in single or mixed DNA conditions. The developed approach enabled the detection of the presence or absence and relative abundance of the HAB-related ribotypes in coastal and microcosm blooms. This study indicates the ability of electronic microarray platform to detect or monitor bacteria in natural and induced environments.

Spironolactone further reduces urinary albumin excretion and plasma B-type natriuretic peptide levels in hypertensive type II diabetes treated with angiotensin-converting enzyme inhibitor.

1. Over the course of treatment with angiotensin-converting enzyme inhibitor (ACEI), plasma levels of aldosterone have been shown to increase and this increase would blunt the effectiveness of the ACEI (aldosterone escape phenomenon). 2. In the present study, we assessed a potential renal benefit of additional aldosterone blockade with spironolactone in hypertensive diabetic patients treated with ACEI showing the phase of aldosterone escape. 3. The present clinical study was a randomized prospective study to assess difference between the clinical effects of spironolactone and furosemide. Thirty hypertensive type II diabetics (DM2) with a urinary alubumin:creatinine ratio (ACR) above 30 mg/g creatinine (showing albuminuria) and plasma B-type natriuretic peptide (BNP) levels above 100 pg/mL (showing mild heart failure) were treated with an ACEI (imidapril 5 mg/day) for 1 year and then randomly divided into two groups, one group receiving additional spironolactone (25 mg/day) treatment and the other receiving furosemide (20 mg/day) treatment. Blood pressure, ACR and plasma BNP levels were monitored in both groups. 4. Treatment with the ACEI reduced ACR initially but, in 1 year, ACR tended to increase. Additional spironolactone treatment progressively reduced ACR, whereas furosemide treatment did not show any effect. Plasma BNP levels were reduced by ACEI and were further reduced by additional spironolactone treatment, but not furosemide treatment. Blood pressure levels in both groups were comparable. 5. In conclusion, additional therapy with spironolactone in ACEI treatment exerts a renoprotective, as well as cardioprotective, effect in hypertensive diabetes.

Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy.

We tested the hypothesis that blockade of angiotensin II type 1 receptors reduces oxidative stress markers in parallel with urinary albumin and type IV collagen excretions. Sixty-six diabetic patients with nephropathy were randomly assigned to either the angiotensin II receptor blocker (ARB; n=33) or trichlormethiazide (n=33) group. The majority of patients had been treated with angiotensin-converting enzyme inhibitors or calcium channel blockers for > or =1 year before the present study. Reduction of blood pressure was not different between the 2 groups, and HbA1c levels did not change over the study period (8 weeks). Treatment with ARB (candesartan 8 mg/day, n=11 or valsartan 80 mg/day, n=22) for 8 weeks reduced the levels of plasma monocyte chemoattractant protein 1, interleukin 6, urinary 8-epi-prostaglandin F2alpha, 8-hydroxydeoxyguanosine, albumin, and type IV collagen, whereas the levels of these markers were not altered with trichlormethiazide (2 mg/day). Significant correlation was observed between the reduction of the urinary 8-epi- prostaglandin F2alpha and 8-hydroxydeoxyguanosine and those of the urinary albumin and type IV collagen. Subjects with large oxidative stress had large reduction rates because of ARB administration and showed large urinary albumin suppression. These results suggest that ARBs reduce oxidative stress and inflammation in diabetic patients independent of their effects on blood pressure. In addition, increases in oxidative stress caused by angiotensin II may play an important role in the progression of diabetic nephropathy. Our results may help to explain the clinical observation that ARB reduces urinary albumin excretion very efficiently in some patients but not in others.