Acute sub-diaphragmatic anterior vagus nerve stimulation increases peripheral glucose uptake in anaesthetized rats.

The sub-diaphragmatic vagus innervates various organs involved in the control of glucose homeostasis including the liver, pancreas and the intestines. In the current study, we investigated the effect of acute electrical stimulation of the anterior trunk of the sub-diaphragmatic vagus on glucose fluxes in anaesthetized adult male rats. After overnight fast, rats underwent either vagus nerve stimulation (VNS+, n = 11; rectangular pulses at 5 Hz, 1.5 mA, 1 msec pulse width) or sham stimulation (VNS-; n = 11) for 120 min under isoflurane anesthesia. Before stimulation, the rats received an i.v. bolus of 1 mL/kg of a sterilized aqueous solution containing 125 mg/mL of D-[6,6-2H2] glucose. Endogenous glucose production (EGP) and glucose clearance rate (GCR) were calculated by kinetic analysis from the wash-out of injected D-[6,6-2H2]glucose from the circulation. VNS+ resulted in lower glucose levels compared to the VNS- group (p < 0.05), with similar insulin levels. EGP was similar in both groups, but the GCR was higher in the VNS+ group compared to the VNS- group (p < 0.001). Circulating levels of the sympathetic transmitter norepinephrine were reduced by VNS+ relative to VNS- treatment (p < 0.01). It is concluded that acute anterior sub-diaphragmatic VNS causes stimulation of peripheral glucose uptake, while plasma insulin levels remained similar, and this is associated with lower activity of the sympathetic nervous system.

Ileal transposition: A non-restrictive bariatric surgical procedure that reduces body fat and increases ingestion-related energy expenditure.

BACKGROUND: Ileal Transposition (IT) was developed as a model to study body weight reduction without the restrictive or malabsorptive aspects of other bariatric surgeries, but the exact mechanisms of the alterations in body weight after IT are not completely understood. OBJECTIVE: To provide a detailed description of the surgical procedure of IT, and describe its effect on energy balance parameters. METHODS: Adult male Lewis rats underwent either IT (IT+) or sham (IT-) surgery. Following surgery body weight and energy intake were monitored. After attaining weight stability (> 30 days), energy expenditure and its components were assessed using indirect calorimetry at a day of fasting, limited intake, and ad libitum intake. At the end of the study body composition analysis was performed. RESULTS: IT+ resulted in transiently reduced energy intake, increased ingestion-related energy expenditure (IEE) and decreased body and adipose tissue weight when compared to IT-. At weight stability, neither energy budget (i.e., energy intake - energy expenditure), nor energy efficiency was different in IT+ rats compared to IT-. CONCLUSION: Our data show that the primary cause of weight reduction following IT+ is a transient reduction in energy intake. If the increased IEE is related to a higher level of satiety, compensatory feeding to bridge body weight difference between IT+ and IT- rats is less likely to occur.

Insulin-like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of ß-hCG and cancer treatment.

BACKGROUND: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy. OBJECTIVES: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients. MATERIALS AND METHODS: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988-1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000-2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy ß-hCG levels. RESULTS: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy ß-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high ß-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001). DISCUSSION: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients. CONCLUSION: Pre-chemotherapy, ß-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone.

Relationship of care staff attitudes with social well-being and challenging behavior of nursing home residents with dementia: a cross sectional study.

Objectives: This study investigates the relationship between attitudes of care staff and social well-being and challenging behavior of residents in long-term dementia care. Methods: The study was based on a cross-sectional design using questionnaires. Care staff members (N = 291) of 15 long-term care facilities in the Netherlands completed the Approaches to Dementia Questionnaire. Additionally, the primary professional caregiver of each participating resident (N = 239) completed an observational questionnaire regarding that resident's behavior, which contained the scale for Social Wellbeing Of Nursing home residents and the Cohen-Mansfield Agitation Inventory. Data were analyzed using multilevel analyses, taking characteristics of residents into account. Results: Attitudes of care staff towards residents with dementia differed between facilities. Further, residents experienced more social well-being and displayed less challenging behavior in facilities where care staff had more hopeful attitudes. Conclusion: This study demonstrates a relationship between attitudes of care staff and resident well-being. The results indicate that it is important to address attitudes towards residents with dementia in the education of (future) care staff. Care processes may also be improved by focusing on the attitudes of care staff. In this way, the well-being of residents with dementia can potentially be improved as well.

Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Unfavourable blood pressure and LDL-cholesterol levels in obese non-diabetic individuals.

BACKGROUND: Early diagnosis and treatment of high blood pressure (BP) and cholesterol is important to reduce cardiovascular risk. We compared BP and LDL-cholesterol (LDL-C) as well as the quality of treatment between obese subjects and normal weight and overweight individuals. METHODS: 87,648 participants of the Lifelines study were categorised according to obesity (normal weight/ overweight/obesity) and age. Mean systolic BP and LDL-C were calculated depending on treatment, BMI, age and sex. RESULTS: In all age groups, except those aged 70-80 years, women had a significantly lower BP than men. Use of BP-lowering medication did not result in BP levels comparable with non-users, except in those aged 70-80 years. Despite medication, the BP was insufficiently controlled in 20-50% of participants. BP was significantly higher in obese vs. normal weight and overweight individuals of all ages, but most apparently in men younger than 50 years. Mean LDL-C varied between 2.5- .0 mmol/l. Despite higher statin use, obese participants had a higher LDL-C than those with a normal weight. Statins abolished the age-dependent LDL-C increase. Many participants did not achieve target LDL-C < 2.5 mmol/l. A small percentage of individuals treated with BP-lowering drugs were also using statins (overall 32% in men, 17% in women). CONCLUSION: Obese individuals, especially men younger than 50, have a higher BP and LDL-C compared with those with overweight and a normal weight. Use of BP-lowering drugs did not revert the BP back to levels normal for the specific age and BMI group, whereas statins abolished the age-related increase in LDL-C. These data suggest that more attention is needed for active screening and treatment of cardiovascular risk factors.

Dumping syndrome after esophageal, gastric or bariatric surgery: pathophysiology, diagnosis, and management.

BACKGROUND: Dumping syndrome, a common complication of esophageal, gastric or bariatric surgery, includes early and late dumping symptoms. Early dumping occurs within 1 h after eating, when rapid emptying of food into the small intestine triggers rapid fluid shifts into the intestinal lumen and release of gastrointestinal hormones, resulting in gastrointestinal and vasomotor symptoms. Late dumping occurs 1-3 h after carbohydrate ingestion, caused by an incretin-driven hyperinsulinemic response resulting in hypoglycemia. Clinical recommendations are needed for the diagnosis and management of dumping syndrome. METHODS: A systematic literature review was performed through February 2016. Evidence-based medicine was used to develop diagnostic and management strategies for dumping syndrome. RESULTS: Dumping syndrome should be suspected based on concurrent presentation of multiple suggestive symptoms after upper abdominal surgery. Suspected dumping syndrome can be confirmed using symptom-based questionnaires, glycemia measurements and oral glucose tolerance tests. First-line management of dumping syndrome involves dietary modification, as well as acarbose treatment for persistent hypoglycemia. If these approaches are unsuccessful, somatostatin analogues should be considered in patients with dumping syndrome and impaired quality of life. Surgical re-intervention or continuous enteral feeding may be necessary for treatment-refractory dumping syndrome, but outcomes are variable. CONCLUSIONS: Implementation of these diagnostic and treatment recommendations may improve dumping syndrome management.

Diagnostic tools for post-gastric bypass hypoglycaemia.

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature.

Conversion of failed laparoscopic adjustable gastric banding to Roux-en-Y gastric bypass is safe as a single-step procedure.

BACKGROUND: Several different procedures have been proposed as a revisional procedure for treatment of failed laparoscopic adjustable gastric banding (LAGB). Laparoscopic Roux-en-Y gastric bypass (LRYGB) has been advocated as the procedure of choice for revision. In this study, we compare the single- and two-step approaches for the revision of failed LAGB to LRYGB. METHOD: All patients who underwent bariatric surgery were included in a prospective database. For the purpose of this study, patients who underwent revisional surgery from LAGB to LRYGB were selected. Records for individual patients were completed by data review. Complication rates and weight development were recorded until 2 years postoperatively. Data were compared between both procedures and with complications rates reported in literature. RESULTS: Revisional gastric bypass surgery was performed in 257 patients. This was done as a planned single-step procedure in 220 (86 %) patients without indications for acute band removal and in 32 patients as a planned 2 step procedure. Five patients were planned as a single-step procedure but were intraoperatively converted to a 2-step procedure based on poor pouch tissue quality. No postoperative mortality occurred in both groups. No differences in early major morbidity and stricture formation were seen between the two groups. Gastric ulceration was more frequently observed after 2-steps procedure (8.5 vs. 1.7 %, p < 0.05). In comparison with data reported in literature, the single-step procedure had similar to lower complication rates. Percentage excess weight loss two years after revisional gastric bypass procedure was, respectively, 53 versus 67 % (p = 0.147) for single- and two-step procedure. CONCLUSION: In patients without indications for acute band removal, the planned conversion of gastric banding to Roux-Y gastric bypass can be safely done in a single-step procedure without increase in morbidity and no difference in postoperative weight loss.

Evaluation of Qualidem: a dementia-specific quality of life instrument for persons with dementia in residential settings; scalability and reliability of subscales in four Dutch field surveys.

OBJECTIVE: To evaluate the scalability and reliability of Qualidem, a quality of life observation instrument rated by professional caregivers of persons with mild to very severe dementia living in residential settings. METHOD: Data from four field surveys in the Netherlands were used. The instrument consists of nine subscales for mild to severe dementia; of which six can be applied in very severe dementia. The Mokken scaling model was used to compute scalability and reliability coefficients for each subscale and dementia group. RESULTS: Seven hundred fifty nine persons with mild to severe dementia and 214 persons with very severe dementia residing in 36 nursing homes and 4 homes for the elderly were included. In general, the subscales for the mild to severely demented group were scalable and (moderate) sufficiently reliable; the results confirmed the results of previous research to develop Qualidem. For the very severe demented group, four out of six subscales were scalable (Care relationship, H = 0.56; Positive affect, H = 0.55; Restless tense behavior, H = 0.42; and Social isolation, H = 0.34); they were also sufficiently reliable to measure quality of life (0.57 ≤ ρ ≤ 0.82). From the other two measured subscales, Social relations was considered not scalable (H = 0.26) and Negative affect was scalable (H = 0.36), but insufficiently reliable (ρ = 0.40). CONCLUSION: Qualidem is an easy to administer and overall moderately sufficient reliable rating scale that provides a quality of life profile of persons with mild to even very severe dementia living in residential settings.

Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue.

BACKGROUND: Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels remains unknown. AIM: To investigate the prevalence of fat-soluble vitamin deficiencies in long-term somatostatin analogue users. METHODS: All acromegaly and carcinoid patients using somatostatin analogues for ≥ 18 months visiting the University Medical Center Groningen between December 2008 and April 2009 were eligible. Vitamin levels of fat-soluble vitamins in blood, clinical and vitamin-dependent laboratory parameters were collected. RESULTS: In all, 19 acromegaly and 35 carcinoid patients were included. Twelve patients experienced steatorrhoea; two carcinoid patients experienced night blindness. Forty-two (78%) were deficient for one or more vitamins, and 32% (n = 17) had multiple deficiencies. Deficiencies for vitamin A, D, E, K1 and E in erythrocytes occurred in 6%, 28%, 15%, 63% and 58% of the patients. Prevalence of vitamin D, E and K1 deficiencies was similar in both patient groups. Treatment duration did not influence vitamin levels. The length of intestinal resection and age correlated negatively with vitamin A levels. CONCLUSIONS: Fat-soluble vitamin deficiencies are frequent during long-term somatostatin analogue treatment. Therefore, fat-soluble vitamins should be monitored in these patients.

[Problems and needs of informal caregivers of persons with dementia: a comparison between the initial stage and subsequent stages of the illness process]. / Problemen en wensen van mantelzorgers van mensen met dementie: een vergelijking tussen de beginfase en latere fasen in het ziekteproces.

This paper investigates whether informal caregivers of persons who have had symptoms of dementia for less than a year, differ from informal caregivers of persons in subsequent stages of dementia. Differences will be investigated in (a) problems experienced in the provision of informal care, (b) the use of ambulatory types of professional support, and (c) the need for additional professional support. Results are based on a survey among 1494 Dutch informal caregivers. Almost all informal caregivers experience problems in caring for a person with dementia, irrespective of the stage of the illness process. Their main problems concern dealing with changes in the behaviour of the person with dementia and dreading the person's admission to a nursing home. Informal caregivers of persons who have had symptoms of dementia for a longer period of time (> 1 year) also experience limitations in their social network. Most persons with dementia receive some kind of professional support. Still, the majority of informal caregivers indicate a need for additional professional support, mainly concerning advice and information. Limiting the available support options for persons with initial symptoms of dementia and their informal caregivers is therefore undesirable. Considering the need for additional support in the initial stage of dementia as well as in subsequent stages, persons with dementia and their informal caregivers should be supported during the entire illness process.

The relationship between organizational culture of nursing staff and quality of care for residents with dementia: questionnaire surveys and systematic observations in nursing homes.

BACKGROUND: Since the 1990s, several studies have shown that organizational culture is an important characteristic in long-term care. However, at the moment little is known about organizational culture and its relationship with quality of care. OBJECTIVES: In this study, the relationship between organizational culture and quality of care in long-term care was investigated using the competing values framework. Thereto, two independent measurements of quality of care were applied: the perceived quality of care by nursing staff of dementia units and the observed quality of care on the units by researchers. DESIGN: The study used a cross-sectional design. SETTINGS: Data were collected on 11 dementia units in 11 Dutch nursing homes. PARTICIPANTS: All nursing staff on the units were asked to complete a questionnaire, of whom 248 staff members responded. The average response rate on the 11 units was 63%. METHODS: Data were collected during two days of field-work on each unit. Systematic observations were performed, and questionnaires were distributed among nursing staff. Data were analyzed using multilevel analyses. RESULTS: Organizational culture was related to both perceived and observed quality of care on the units. Units that are characterized by a clan culture provide better quality of care, both in the eyes of the nursing staff as in the eyes of outsiders. Market culture, compared to clan culture, is negatively related to quality of care in this sample. CONCLUSIONS: The results indicate that organizational culture in long-term dementia care is important for organizational performance.

Abnormal liver function in relation to hemodynamic profile in heart failure patients.

BACKGROUND: We studied the relation between liver function abnormalities and hemodynamic profile in patients with heart failure (HF). METHODS AND RESULTS: In 323 HF patients, liver function was determined by aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase, and direct and total bilirubin (Bili dir, Bili tot). Central venous pressure (CVP) and cardiac index (CI) were determined invasively. Follow-up consisted of time to all-cause mortality. Mean age was 53 +/- 15 years, and 60% were male. In multivariable analysis, all liver function tests related to CVP, but higher CVP was predominantly related to GGT (r = 0.336, P < .001) and Bili dir (r = 0.370, P < .001). Only elevated AST (r =-0.177, P < .01), ALT (r = -0.130, P < .05), and Bili tot (r = -0.158, P < .01) were associated with both low CI and elevated CVP. The prognostic value of abnormal liver function tests was related to their interaction with CI and CVP. CONCLUSIONS: Elevated liver function tests mainly indicate higher CVP, whereas only the presence of elevated AST, ALT, or Bili dir may indicate a low CI. The absence of prognostic information in the presence of invasive hemodynamic measurements suggests that abnormal liver function tests in HF reflect a poor hemodynamic status.

Development and initial testing of an instrument to establish eating profiles of clients in nursing homes or elderly homes.

"Eating profiles" can be defined as types of clients distinguished by combinations of food preferences, consumption patterns, and preferences for ambiance. The purpose of this article is to describe the development and initial testing of an instrument to establish eating profiles of residents of nursing homes or elderly homes. We constructed a 35-item, 4-subscale questionnaire. This self-administered, usable instrument derived five eating profiles from clients' perspectives. Insight in eating profiles is important for facility managers to ascertain that the food, dinner service, and ambiance are adequately tailored to the residents' preferences.

[Combined vision and hearing impairment: in an estimated 30,000-35,000 people aged 55 years or over in The Netherlands]. / Gecombineerde visus- en gehoorbeperking: naar schatting bij 30,000-35,000 55-plussers in Nederland.

OBJECTIVE: To determine the number of older people with acquired dual sensory impairment (DSI) in The Netherlands. DESIGN: Combination of studies in the general population and in relevant subpopulations. METHOD: Eight databases derived from recent studies on older persons with vision and hearing data on Dutch subjects aged 55 years or over were selected for further analysis. The measurement methods included self-reports, clinical measurements and observations. The prevalences of DSI were calculated for the general population, the non-institutionalised population, and subgroups such as older people in nursing homes and homes for the elderly. The calculated prevalences were extrapolated to the overall Dutch population. RESULTS: For the non-institutionalised population of 55 years and older, the prevalences of acquired DSI in two different data sets were 0.4% (95% CI: 0.2-0.6) and 0.6% (95% CI: 0.3-0.8), respectively. Among the inhabitants of homes for the elderly these percentages were 5.4% (95% CI: 0.9-9.9) and 5.5% (95% CI: 3.8-7.2), and in nursing homes they were 12.7% (95% CI: 9.7-15.7) and 16.7% (95% CI: 14.6-18.8). Acquired DSI was most common in persons 85 years of age and older. It was estimated that the number of people aged 55 years and over with acquired DSI in The Netherlands is 30,000 to 35,000. CONCLUSION: DSI is particularly a problem of the oldest old. An integrated approach to the visual and hearing problems of these subjects is essential.