Symptoms, symptom relief and support in COVID-19 patients dying in hospitals during the first pandemic wave.

BACKGROUND: At the time of the first wave of the COVID-19 pandemic in Sweden, little was known about how effective our regular end-of-life care strategies would be for patients dying from COVID-19 in hospitals. The aim of the study was to describe and evaluate end-of-life care for patients dying from COVID-19 in hospitals in Sweden up until up until 12 November 2020. METHODS: Data were collected from the Swedish Register of Palliative Care. Hospital deaths during 2020 for patients with COVID-19 were included and compared to a reference cohort of hospital patients who died during 2019. Logistic regression was used to compare the groups and to control for impact of sex, age and a diagnosis of dementia. RESULTS: The COVID-19 group (1476 individuals) had a lower proportion of women and was older compared to the reference cohort (13,158 individuals), 81.8 versus 80.6 years (p < .001). Breathlessness was more commonly reported in the COVID-19 group compared to the reference cohort (72% vs 43%, p < .001). Furthermore, anxiety and delirium were more commonly and respiratory secretions, nausea and pain were less commonly reported during the last week in life in the COVID-19 group (p < .001 for all five symptoms). When present, complete relief of anxiety (p = .021), pain (p = .025) and respiratory secretions (p = .037) was more often achieved in the COVID-19 group. In the COVID-19 group, 57% had someone present at the time of death compared to 77% in the reference cohort (p < .001). CONCLUSIONS: The standard medical strategies for symptom relief and end-of-life care in hospitals seemed to be acceptable. Symptoms in COVID-19 deaths in hospitals were relieved as much as or even to a higher degree than in hospitals in 2019. Importantly, though, as a result of closing the hospitals to relatives and visitors, patients dying from COVID-19 more frequently died alone, and healthcare providers were not able to substitute for absent relatives.

Dying from COVID-19 in nursing homes-sex differences in symptom occurrence.

BACKGROUND: Coronavirus disease 2019 (COVID-19), is a disease with diverse presentation. Several studies have shown different occurrence of symptoms for women and men, but no studies have been found examining sex differences in clinical presentation for nursing home residents dying from COVID-19. The objective of this study was to describe sex and age differences and the impact of a dementia diagnosis on symptom occurrence during the last week in life for persons dying from COVID-19 in nursing homes. METHODS: This is a population-based retrospective study based on data from the Swedish Register of Palliative Care. A total of 1994 residents aged 65 or older who died from COVID-19 in nursing homes were identified. The impact of sex, age and a dementia diagnosis on six different symptoms was analysed using chi2-test and multivariate logistic regression. RESULTS: Residents dying from COVID-19 were more often men (p < .002). Men more often had dyspnoea and death rattles (p < .001). Nausea was more common in women (p < .001). No sex differences in the occurrence of pain, anxiety or confusion were seen. Dyspnoea and nausea were less commonly reported in residents with dementia (p < .001). CONCLUSIONS: We found sex differences in symptom presentation for fatal COVID-19 in nursing home settings which remained after adjusting for age. Residents with a dementia diagnosis had fewer symptoms reported before death compared to those without dementia. Clinical presentation of fatal COVID-19 differs between women and men in nursing homes. Residents with fatal COVID-19 present with more unspecific and less prominent symptoms when also suffering from dementia.

COVID-19: Symptoms in Dying Residents of Nursing Homes and in Those Admitted to Hospitals.

Objective: To compare symptom prevalence and relief in residents who died in nursing homes with residents who were acutely referred to hospitals. Design: Data on symptoms during the last week of life from the Swedish Register of Palliative Care (SRPC). Setting and Subjects: Nursing homes (n = 1903 deaths) and hospitals in Sweden (n = 202 nursing home residents who were admitted to hospital before death). Data were retrieved on August 24, 2020. Results: Residents who died in hospitals had more breakthrough symptoms of breathlessness (60% vs. 31%, p < 0.0001) and delirium (41% vs. 25%, p < 0.0001) than those who died in nursing homes. When symptoms were present, complete symptom relief was seen less often in hospitals compared with nursing homes (breathlessness, 28% vs. 47%, p < 0.001; delirium, 10% vs. 35%, p < 0.0001; respiratory secretions, 30% vs. 55%, p < 0.0001). Conclusion: Despite access to oxygen and pharmacologic/nonpharmacologic therapies in hospitals, symptom relief in dying nursing home residents acutely admitted to hospitals was lower compared with those who died in nursing homes, possibly because of differences in patient characteristics.

Were Clinical Routines for Good End-of-Life Care Maintained in Hospitals and Nursing Homes During the First Three Months of the Outbreak of COVID-19? A National Register Study.

CONTEXT: Although the coronavirus disease 2019 (COVID-19) pandemic might affect important clinical routines, few studies have focused on the maintenance of good quality in end-of-life care. OBJECTIVES: The objective was to examine whether adherence to clinical routines for good end-of-life care differed for deaths because of COVID-19 compared with a reference cohort from 2019 and whether they differed between nursing homes and hospitals. METHODS: Data about five items reflecting clinical routines for persons who died an expected death from COVID-19 during the first three months of the pandemic (March-May 2020) were collected from the Swedish Register of Palliative Care. The items were compared between the COVID-19 group and the reference cohort and between the nursing home and hospital COVID-19 deaths. RESULTS: About 1316 expected deaths were identified in nursing homes and 685 in hospitals. Four of the five items differed for total COVID-19 group compared with the reference cohort: fewer were examined by a physician during the last days before death, pain and oral health were less likely to be assessed, and fewer had a specialized palliative care team consultation (P < 0.0001, respectively). Assessment of symptoms other than pain did not differ significantly. The five items differed between the nursing homes and hospitals in the COVID-19 group, most notably regarding the proportion of persons examined by a physician during the last days (nursing homes: 18%; hospitals: 100%). CONCLUSION: This national register study shows that several clinical routines for end-of-life care did not meet the usual standards during the first three months of the COVID-19 pandemic in Sweden. Higher preparedness for and monitoring of end-of-life care quality should be integrated into future pandemic plans.

Symptom Relief Is Possible in Elderly Dying COVID-19 Patients: A National Register Study.

Background: Increasing numbers of people dying from COVID-19 are reported, but data are lacking on the way they die. Objective: To study symptoms and symptom relief during the last week of life, comparing nursing homes with hospitals. Design: The Swedish Register of Palliative Care with national coverage was used. Breakthrough symptoms were registered as Yes/No. Symptom relief was recorded on a 3-grade scale as complete-partial-no relief. All deaths in COVID-19 were contrasted to deaths in a reference population (deaths 2019). Deaths at nursing homes were compared with deaths in hospitals. Setting and Subjects: All deaths in hospitals or nursing homes (n = 490) were analyzed. Deaths in other settings (specialized palliative care wards [n = 11], in palliative home care [n = 2], or in their own homes [n = 8]) were excluded (n = 21). Only patients with expected deaths (n = 390) were entered in the final analysis. Results: Breathlessness as a breakthrough symptom was more common in COVID-19 patients than in the 2019 reference population (p < 0.001) and relief of breathlessness, as well as anxiety, delirium, and death rattles was less successful in COVID-19 patients (p < 0.05 to p < 0.01 in different comparisons). Patients were older in nursing homes than in hospitals (86.6 years vs. 80.9 years, p < 0.001) and more often female (48% vs. 34%, p < 0.001). Breakthrough of breathlessness was much more frequently reported in hospital settings than in nursing homes, 73% versus 35% (p < 0.0001), and complete relief was more rarely possible in hospitals, 20% versus 42% (p < 0.01). The proportion of partial relief+complete relief was comparable, 92% versus 95% (ns). Also, anxiety and pain were more often completely relieved in nursing homes (p < 0.01 in both comparisons). Conclusion: The lower symptom prevalence in nursing homes may be explained by elderly frail residents dying already in the first phase of the COVID-19 disease, before acute respiratory distress syndrome develops.

Dying From COVID-19: Loneliness, End-of-Life Discussions, and Support for Patients and Their Families in Nursing Homes and Hospitals. A National Register Study.

CONTEXT: Preparation for an impending death through end-of-life (EOL) discussions and human presence when a person is dying is important for both patients and families. OBJECTIVES: The aim was to study whether EOL discussions were offered and to what degree patients were alone at time of death when dying from coronavirus disease 2019 (COVID-19), comparing deaths in nursing homes and hospitals. METHODS: The national Swedish Register of Palliative Care was used. All expected deaths from COVID-19 in nursing homes and hospitals were compared with, and contrasted to, deaths in a reference population (deaths in 2019). RESULTS: A total of 1346 expected COVID-19 deaths in nursing homes (n = 908) and hospitals (n = 438) were analyzed. Those who died were of a more advanced age in nursing homes (mean 86.4 years) and of a lower age in hospitals (mean 80.7 years) (P < 0.0001). Fewer EOL discussions with patients were held compared with deaths in 2019 (74% vs. 79%, P < 0.001), and dying with someone present was much more uncommon (59% vs. 83%, P < 0.0001). In comparisons between nursing homes and hospital deaths, more patients dying in nursing homes were women (56% vs. 37%, P < 0.0001), and significantly fewer had a retained ability to express their will during the last week of life (54% vs. 89%, P < 0.0001). Relatives were present at time of death in only 13% and 24% of the cases in nursing homes and hospitals, respectively (P < 0.001). The corresponding figures for staff were 52% and 38% (P < 0.0001). CONCLUSION: Dying from COVID-19 negatively affects the possibility of holding an EOL discussion and the chances of dying with someone present. This has considerable social and existential consequences for both patients and families.

Occurrence of substance P in bone repair under different load comparison of straight and angulated fracture in rat tibia.

Substance P (SP) has been shown in vitro to stimulate both formation and resorption of bone. This seemingly contradictory observation could be explained by in vivo variations in skeletal loading and rate of bone turnover, features which may be explored during different phases of fracture healing. In 50 SD rats, the right tibia was fractured and fixed with an intramedullary pin in straight alignment and in anterior angulation resulting in a convex and concave side under different load. Fracture repair was assessed by radiography, histology, and semi-quantitative immunohistochemistry of SP nerve fiber occurrence at days 7, 21, 35, 56, and 84 post-fracture. During regeneration, days 7-35, abundant SP-nerve ingrowth was observed in the fracture callus reaching a side-symmetrical peak at day 21 in straight fractures. In angulated fractures, the SP peak was also observed at day 21 on the concave loaded side, but not until day 35 on the convex unloaded side. Each SP-peak coincided with cortical bridging. During remodeling, days 35-84, a side-symmetrical disappearance of SP-positive fibers was seen in straight fractures. The same pattern was seen on the concave loaded side of angulated fractures. However, on the convex unloaded side, where resorption now took place, SP-fibers remained until the end of the experiment. Our study suggests that neuronal SP during bone regeneration has a stimulatory role on bone formation, while during remodeling increased SP fiber density in unloaded areas may be related to bone resorption.

Coevolution of non-fertile sperm and female receptivity in a butterfly.

Sexual conflict can promote rapid evolution of male and female reproductive traits. Males of many polyandrous butterflies transfer nutrients at mating that enhances female fecundity, but generates sexual conflict over female remating due to sperm competition. Butterflies produce both normal fertilizing sperm and large numbers of non-fertile sperm. In the green-veined white butterfly, Pieris napi, non-fertile sperm fill the females' sperm storage organ, switching off receptivity and thereby reducing female remating. There is genetic variation in the number of non-fertile sperm stored, which directly relates to the female's refractory period. There is also genetic variation in males' sperm production. Here, we show that females' refractory period and males' sperm production are genetically correlated using quantitative genetic and selection experiments. Thus selection on male manipulation may increase the frequency of susceptible females to such manipulations as a correlated response and vice versa.

Expanded HSAN4 phenotype associated with two novel mutations in NTRK1.

Hereditary sensory and autonomic neuropathy type IV (HSAN4) is a severe autosomal recessive disorder characterized by childhood onset of sensory and autonomic dysfunction leading to hyperthermia, recurrent infections and physical impairment due to complications of osteoarthritis. Cognitive impairment and aggressive behaviour is common. HSAN4 is caused by mutations in the NTRK1 gene coding for the tyrosine kinase receptor A. We present detailed description of a rare, mild HSAN4 phenotype associated with two novel NTRK1 mutations. This Swedish patient presents with an adult onset of painful Charcot arthropathy, prolonged wound healing, discrete polyneuropathy, hypohidrosis without further autonomic dysfunction and no cognitive affection.

Clinical characteristics of carbohydrate-deficient transferrin (%disialotransferrin) measured by HPLC: sensitivity, specificity, gender effects, and relationship with other alcohol biomarkers.

AIMS: The sensitivity and specificity of the relative disialotransferrin amount (%DST), considered the primary single target for measurement of the alcohol biomarker carbohydrate-deficient transferrin (CDT), were compared with the absolute CDT amount determined by the CDTect assay and with GGT and AST. METHODS: Serum samples (n = 1387) were collected within the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. The subjects had been classified as "nondrinkers" (26%), "light/moderate drinkers" (50%), or "heavy drinkers" (24%) by use of the WHO/ISBRA Interview Schedule. An HPLC candidate reference method for CDT was used to quantify individual transferrin glycoforms. RESULTS: No gender difference in %DST was noted for nondrinkers, but light/moderate and heavy drinking males had significantly higher levels than females. Of the alcohol biomarkers examined, %DST showed the strongest correlation with self-reported alcohol intake, except for female heavy drinkers. The area under the %DST ROC curve for male (0.83) and female (0.82) heavy drinkers was significantly higher compared with CDT by CDTect (0.68) and GGT (0.69). At the 40, 60, or 80 g ethanol/day thresholds, %DST showed lower test sensitivity in women but there was no significant gender difference in overall accuracy according to ROC curve analysis. CONCLUSIONS: %DST measured by HPLC showed overall higher sensitivity for "heavy drinking" and better correlation with recent high alcohol intake, compared with the absolute CDT amount, and GGT and AST. The observation that several "light/moderate drinkers" had elevated %DST levels and some also a measurable asialotransferrin indicated misclassification with the WHO/ISBRA Interview Schedule and emphasize the limitations of self-reports of drinking.

HPLC evaluation of clinical and pharmacological factors reported to cause false-positive carbohydrate-deficient transferrin (CDT) levels.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) is an alcohol biomarker used for detection and follow-up of excessive alcohol consumption. This HPLC study evaluated some clinical conditions and medications previously suggested to interfere with and cause non-alcohol related elevations of CDT. METHODS: Serum samples were collected from patients with end-stage liver disease (n=50), type 2 diabetes mellitus (n=46), cystic fibrosis (n=24), an elevated C-reactive protein level (CRP>100 mg/L; n=15), and from patients taking enzyme inducing or non-enzyme inducing antiepileptic drugs (n=43). Subjects with known or suspected alcohol-related problems were excluded. A sensitive and specific HPLC candidate CDT reference method was used to determine the relative amount of disialotransferrin to total transferrin. RESULTS: Of the 178 samples, 9 (5%) had a %disialotransferrin level > or =1.8% (>97.5th percentile) and were considered CDT positive. The highest frequency of elevated results was found in patients with end-stage liver disease (12%, n=6), including 3 with hemochromatosis, 1 with hepatitis C, 1 with autoimmune hepatitis and 1 with unspecified liver disease and cirrhosis. The other elevated %disialotransferrin results were from 2 patients taking enzyme-inducing antiepileptic drugs and 1 with type 2 diabetes. Five of 8 examined %disialotransferrin positive samples were also positive for ethyl glucuronide (EtG). CONCLUSION: This HPLC study found an overall low frequency of elevated %disialotransferrin levels in the clinical conditions and medications examined. Previous reports of frequent false-positive CDT results thus seem to be connected with the analytical methodology used rather than representing true clinical or pharmacological interferences.

Influence of alcohol use, ethnicity, age, gender, BMI and smoking on the serum transferrin glycoform pattern: implications for use of carbohydrate-deficient transferrin (CDT) as alcohol biomarker.

BACKGROUND: An alcohol-induced change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker for detection and follow-up of heavy alcohol consumption. Besides studying the effects of drinking, this study evaluated any baseline differences in the transferrin pattern in relation to ethnicity, age, gender, body mass index (BMI) and smoking, as these could be confounders causing bias in CDT testing. METHODS: The transferrin glycoform pattern was determined in 1387 sera (68% men, 32% women) collected in Australia, Brazil, Canada, Finland and Japan from subjects classified as non-drinkers, light/moderate drinkers, or heavy drinkers by use of the WHO/ISBRA Interview Schedule. The iron-saturated glycoforms were separated by an HPLC candidate reference method, and the relative amounts of individual glycoforms to total transferrin were determined. RESULTS: In non-drinkers, the differences in the serum transferrin glycoform pattern in relation to ethnicity, age, gender and BMI were small and mostly not statistically significant. A higher disialotransferrin level in smokers compared with non-smokers could largely be explained by a higher alcohol intake in smokers. In the drinking subgroups, the main CDT glycoform disialotransferrin showed a positive correlation (r=0.80) with asialotransferrin, and disialo- and asialotransferrin a negative correlation with tetrasialotransferrin, that was dependent on the alcohol consumption level. CONCLUSIONS: With respect to CDT testing, the results indicated that adjustment of reference intervals for disialotransferrin and CDT in relation to ethnicity, age, gender, BMI and smoking is not required.

Site-specific CGRP innervation coincides with bone formation during fracture healing and modeling: A study in rat angulated tibia.

Sensory neuropeptide involved in local bone turnover is known, but poorly understood. In the present study, we analyze the occurrence of neuronal CGRP during healing and modeling of straight and angular tibial fractures in 74 rats. Bone healing and modeling was assessed by radiography and reinnervation by semi-quantitative immunohistochemistry method at fracture site between 1-12 weeks postfracture. The regenerating nerve fibers containing CGRP were observed in fracture callus as well as in close proximity to chondrocytes, with woven bone in both fractures already at week 1. Notably, it located predominantly on the concave side of angulated fracture in the manner of sprouting into bone from weeks 3 to 5 postfracture. In both fractures, fracture calluses peaked radiographically at week 3 postfracture. In angulated fracture, a reduction of 11% in callus thickness on convex side and an increase of 365% on concave side were noted from weeks 3 to 12. A 27-fold increase in total neuronal CGRP in straight fracture and 38-fold increases in angular fracture compared to intact bone was observed at week 3. In both types of fracture, neuronal CGRP was greater on the concave side than the convex; this difference was more pronounced in the angulated fracture. CGRP immunoreactivity clearly coincides with amount of new bone formation especially on the concave side of angulated fracture. The combined results suggest that fracture evokes an intense, localized in-growth of new nerve fibers containing CGRP, which may prove to be a prerequisite of fracture healing and modeling.

Effect of bicarbonate on muscle protein in patients receiving hemodialysis.

BACKGROUND: Metabolic acidosis stimulates whole-body net protein breakdown in healthy adults and patients with kidney failure, but few studies investigated how acidosis affects protein metabolism in individual tissues, such as skeletal muscle. METHODS: We evaluated the effect of metabolic acidosis on protein turnover in skeletal muscle, assessed by means of phenylalanine kinetics and free amino acid concentrations in plasma and muscle. Long-term hemodialysis patients (n = 16) were divided into 2 groups in an open crossover study design. In group A, we administered bicarbonate supplements and increased blood standard bicarbonate levels from 17.8 +/- 0.03 to 27.1 +/- 1.2 mEq/L (17.8 +/- 0.03 to 27.1 +/- 1.2 mmol/L). In group B, we decreased bicarbonate supplements, which caused a decrease in standard bicarbonate levels from 26.6 +/- 0.7 to 18.6 +/- 0.3 mEq/L (26.6 +/- 0.7 to 18.6 +/- 0.3 mmol/L). RESULTS: Net phenylalanine efflux from leg tissues (muscle) was significantly less when acid-base balance was corrected compared with acidosis (10.8 +/- 1.5 versus 18.6 +/- 3.8 nmol/min/100 g tissue; P = 0.014), as was the rate of phenylalanine appearance (28.3 +/- 3.0 versus 38.4 +/- 5.9 nmol/min/100 g tissue; P = 0.016); the rate of phenylalanine disposal was unchanged. Cortisol and C-reactive protein levels in blood were unchanged after correction of acidosis, as were levels of messenger RNAs encoding components of the ubiquitin-proteasome pathway in muscle biopsy specimens. CONCLUSION: Our findings indicate that acidosis increases protein breakdown in skeletal muscle, but additional studies are needed to identify the pathways stimulated to degrade muscle protein in response to acidosis.

Determination of carbohydrate-deficient transferrin in human serum using the Bio-Rad %CDT by HPLC test.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) in serum is a biomarker used to identify individuals with sustained, heavy alcohol consumption. This study evaluated the performance of a new commercial method for CDT, the Bio-Rad %CDT by HPLC test, that measures relative amounts of separate transferrin glycoforms in proportion to total transferrin. METHOD: The samples used were two human serum pools (low/high disialotransferrin), 150 clinical sera with low to highly elevated disialotransferrin values, and 18 genetic transferrin variants. Glycoforms are separated on a gradient HPLC system, followed by specific measurement of the iron-transferrin complex at 460 nm. Comparison was made with an HPLC candidate reference method on an Agilent 1100 LC system. RESULTS: The Bio-Rad %CDT by HPLC test allowed for reproducible separation and quantification of the transferrin glycoforms within approximately 6 min. Genetic variants were readily identified. For the low and high serum pool, the total CV was 8.5% and 4.3%, respectively. The relative amounts of disialotransferrin, the main CDT glycoform, were in good agreement with the results of the HPLC candidate reference method (r(2)=0.998, p<0.0001). CONCLUSIONS: The present results demonstrated that the Bio-Rad %CDT by HPLC test is appropriate for confirmatory and routine %CDT testing in human serum, with the added advantage over previously published HPLC methods of an improved serum sample pretreatment and a shorter total analysis time.

Opioid peptides and receptors in joint tissues: study in the rat.

Using immunohistochemical and biochemical techniques, the occurrence of endogenous opioid peptides and their receptors in normal rat bone and joint tissues was investigated. Opioid receptors were detected, quantified, and characterized in homogenates from capsule/synovium and periosteum using radioligand binding assays. Receptor binding of the nonselective opioid [3H]naloxone to tissue homogenates was stereospecific and saturable, showing similar characteristics to that of brain tissue, although with lower binding capacities. By immunohistochemistry, the neuronal occurrence of four different enkephalins was demonstrated in synovium, bone marrow, periosteum, and juxta-articular bone, whereas no neuronal dynorphin immunoreactivity was detected. Double-staining studies disclosed that enkephalins coexisted with substance P in primary afferent fibers. The applied techniques can be used to assess changes in the distribution of endogenous opioids and their receptors in joint tissues in conditions associated with pain and inflammation. The endogenous opioid system now demonstrated might be targeted and exploited therapeutically to obtain peripheral control of symptoms in joint disorders.

Extracellular volume changes and blood pressure levels in hemodialysis patients.

BACKGROUND: Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post-HD body weight (BW) over a period of 3 to 4 months. METHODS: During a period of 3-4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143-141 mmol/L to 139-138 mmol/L. Extracellular volume (ECV) was measured with a multiple-frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical. RESULTS: Group 1 showed a significant reduction during the entire 48-hour period in systolic (156 +/- 16 mmHg vs. 140 +/- 14 mmHg, P = 0.030) and diastolic BP (97 +/- 12 mmHg vs. 87 +/- 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 +/- 13 vs. 105 +/- 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 +/- 15 mmHg vs. 138 +/- 14 mmHg, P = 0.007; diastolic BP 97 +/- 12 mmHg vs. 85 +/- 9 mmHg, P = 0.009) than during the day (157 +/- 18 mmHg vs. 142 +/- 15 mmHg, P = 0.067; diastolic BP 97 +/- 13 mmHg vs. 90 +/- 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48-hour period (76 +/- 24% vs. 46 +/- 28%, P = 0.043) as well as in night systolic load (75 +/- 21% vs. 41 +/- 30%, P = 0.015) and night diastolic load (67 +/- 32% vs. 39 +/- 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2. CONCLUSIONS: The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.