The Curaçao Cohort Studies

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New roles for renin in heart failure and cardio-renal interaction

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Longer-term effects of ADAS use on driving performance of healthy older drivers and drivers diagnosed with Parkinson’s disease

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Novel strategies for enhancing the efficacy of therapeutic immunization against cancer

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The toxic effects of ¹³¹I-therapy on bone marrow in patients with differentiated thyroid carcinoma.

Introduction.
DTC is the most common endocrine malignancy with a rising prevalence. Due to the favorable prognosis of DTC there is an increasing interest in quality of life of these patients. Treatment with ¹³¹I follows after (total) thyroidectomy, and is associated with better DTC survival. However, this therapy is also associated with possible adverse effects on the bone marrow, though data about this subject are scarce in the literature.
Purpose.
The primary aim of this retrospective study was to determine if changes in blood count parameters occur after treatment with ¹³¹I. The secondary aim was to define the characteristics of patients with blood count drops, including TNM-classification, histology, age, cumulative ¹³¹I dose.
Methods.
All DTC patients, treated with ¹³¹I in the UMCG between January 1989 and July 2013 were analyzed. Patients without baseline or follow-up data and/or co-morbidity that could have caused the blood count drops were excluded. Mean values of Hb, leukocytes and platelets were analyzed to estimate significant changes in blood counts, 3 and 6 months after each treatment. After this, we determined which patient characteristics were associated with the occurrence of anaemia, leukopenia and thrombocytopenia after the cumulative dose. RESULTS. 586 patients fulfilled the inclusion criteria. Male: female ratio was 26.5:73.5. The mean±SD age of the patients was 49.35±17.6 years and the median received cumulative dose was 300 mCi (IQR=150-350). A significant increase of Hb and decrease of leukocyte-count occurred after the initial dose. After the second ¹³¹I treatment, also platelet counts decreased significantly. Decreases of leukocyte and platelet counts remained during the rest of the treatments. All mean decreases fell within the normal range. Patient characteristics associated with blood count drops (below value of reference), were an older age (>45 years), a large primary tumour (T4), distant metastases and a high cumulative ¹³¹I dose (<450 mCi).
Conclusion.
This study shows a significant decline of mean leukocyte and platelet counts after treatment with ¹³¹I in DTC patients. Although these mean declines still fall within the normal range, clinicians should be aware of this phenomenon in patients with low bone marrow reserve or patients with risk factors associated with blood count drops.

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Identification of a prospective marker for JAK2 V617F mutant cells from patients with myeloproliferative neoplasms and characterisation of haematopoietic stem cell heterogeneity.

The myeloproliferative neoplasms (MPNs), including polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis (MF), are clonal disorders originating from a mutation or series of mutations in haematopoietic stem and progenitor cells. In 2005, a unique gain of function mutation was discovered in a substantial proportion of MPN patients, called JAK2 V617F. In addition, the majority of JAK2 V617F negative MPN patients have recently been shown to carry a somatic mutation in CALR. The first part of this study focuses on the identification of prospective markers of JAK2 V617F mutant primitive cells from patients’ blood samples with the goal of expanding the tools available to study mutant HSCs. Using a large cell surface marker screen, twenty putative candidates have been selected and seven of them are further explored by means of sequencing colonies from additional patients’ blood samples for their JAK2 status. Three of the seven initial candidates were excluded based on inconsistent sequencing patterns, which means that they are not JAK2 specific, but the other four continue to look promising. The second part of this study evaluates normal HSC heterogeneity in both a short-term as well as a long-term clonal assay. Differences in clone size and the time of cell appearance have been shown to be able to define distinct subpopulations of primitive haematopoietic cells. This work will enable specific selection of the most primitive HSC subsets in future projects.

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Voorspellende waarden in darmweefsel op het optreden van klinische naadlekkage bij colorectale chirurgische ingrepen.

Background:
Anastomotic leakage after colorectal surgery is a severe complication, leading to morbidity, reinterventions, prolonged hospital stay and, in some cases, even death. Though,
early stages of anastomotic leakages are hard to detect.
The aim of this study is to find molecular biological factors in the bowel that could predict the development of anastomotic
leakage. Factors like Matrix MetalloProteinases (MMP’s) and the intestinal microbiome.
Methods:
Tissue of the bowel was peroperatively collected during a multicentre trial (Csealtrial). RNA and DNA were isolated from these samples, of which gene-expression of
multiple MMP’s and the presence of bacteria has been investigated. Furthermore,
immunohistochemical stainings on these samples with MMP-antibodies were performed.
Results and Conclusion:
Gene-expression of multiple MMP’s (MMP-1, -2, -3, -9, -14, -19 en -25) has been found in the samples of all patients. MMP-1 showed a significant difference (P<0.01) between the two research groups, with the gene-expression in the control group higher than in the group with patients developing anastomotic leakage. Additional to that, we
found that a bacterial family, the Lachnospiraceae, was significantly correlated with the development of post-operative anastomotic leakage in our research groups. Also a correlation between these bacteria and an increased Body Mass Index (BMI) was found. Moreover, BMI also correlated with the development of anastomotic leakage.
In conclusion, a high presence of Lachnospiraceae in the bowel tissue around the anastomosis may predispose the
development of anastomotic leakage.

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Het bepalen van de patiënttevredenheid, functionaliteit en de relatie met bone-union na een tibio-talo-calcaneaire artrodese met de “Keulse pen”, een retrospectieve studie.

Background:
a tibio-talo-calcaneaire arthrodesis is the final solution for patients with severe ankle and subtalair pain, and functional complaints. These complaints have different origins, such as primary osteoarthritis or secondary due to trauma, rheumatoid arthritis or instability. Retrograde intramedullary nailing is one of the most used techniques for arthrodesis in the past years. The aim of this study was to assess the union rate and the postoperative satisfaction and functionality in patients operated with a Cologne nail.
Methods:
this is a retrospective study within Isala hospital, Zwolle. Seventy-three patients underwent an arthrodesis with a Cologne nail between March 2000 and October 2012, all operated by the same orthopedic surgeon. The average age was 59 years (22 – 86) with a mean follow up of 5 years (1 – 13). The minimal follow up was 1 year. The primary outcomes were the American Orthopaedic Foot and Ankle Society (AOFAS), ankle/hindfoot questionnaire and the pre- and postoperative VAS-satisfaction score. Secondary outcome was the union rate assessed by X-rays of the ankle 6, 12 and 52 weeks postoperative.
Results:
the difference between the pre- and postoperative VAS-satisfaction score was 3.7 points (3.0 – 6.6). Eighty-three percent of the patients were clearly more satisfied after the surgery. The AOFAS was 47.6 (scale 0 – 86). Eighty-one percent of the patients reported no or very light pain during follow-up. Eleven re-operations were performed, 9 infections were registered and 1 lower leg amputation was executed as direct result of the double-artrodesis. The union rate for the ankle and subtalar joints after arthodesis was 97.7 % and 90.5 % 1 year postoperative. No correlations were found between fusion(time) and AOFAS score or VAS-satisfaction score.
Conclusion:
the Cologne nail ‘Keulse pen’ is a frequently used instrument for tibio-talo-calcaneaire arthrodesis. Arthrodesis with a Cologne nail is associated with high union scores and high postoperative satisfaction rates in patients.

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De efficiëntie van de digitale auto anamnese en de ervaring met deze vragenlijst op de polikliniek urogynaecologie.

Introduction.
The ‘digitale auto anamnese (DAA)’ is being used for several years at the outpatient clinic for urogynaecology at the Martini Hospital Groningen (The Netherlands) to evaluate patients with complaints of pelvic floor dysfunction. This questionnaire is a collection of several shorter validated questionnaires like the ‘urogenital distress inventory’, the ‘defecatory distress inventory’, the ‘incontinence impact questionnaire’ and the RAND 36, a widely used quality of life questionnaire. Before the introduction of this digital version, an analogue questionnaire was used. Current research regarding urogynaecology questionnaires has focused particularly on the predictive value of these questionnaires and on epidemiological issues concerning urogynecological diseases. Less is known about the benefits or disadvantages of a questionnaire. For example whether the DAA increases the efficiency of a consultation and in which way it contributes to the anamnesis. The overall experience and satisfaction of patients and hospital staff regarding the DAA hasn’t been studied either.
Aim.
To examine the efficiency of the DAA and the experience of the patients and staff with this questionnaire. To assess its contribution to a complete and well formulated medical history.
Method.
In a period of three months all patients with a referral for pelvic floor dysfunction were randomized for receiving the digital questionnaire (DAA+) or not (DAA-). The efficiency of the consultation was defined as the time needed for the different parts of the appointment and the number of appointments after the first contact regarding the same complaint. To examine the totality of the medical history we scored if the staff member mentioned complaints regarding the domains of prolapse (POP), urine incontinence (UI), micturition, defecation, overactive bladder (OAB) and sexuality. Patient experience was examined by a telephone survey and the experience of staff was explored by an interview at the end of the research period.
Results.
A total of 128 patients were randomized, 64 DAA+ and 64 DAA-. The medical history is significantly shorter (MD (Mean difference) 01m32s, 95% CI (Confidence interval) 0:00:23 – 0:02:41, p=0.009) and the time used for explanation of the condition and treatment is significantly longer (MD -01m21s, 95% CI -0:02:37 – -0:00:06, p=0.035) in the DAA+ group. We found no differences between the time of the complete appointment and the number of extra visits of both groups. After correction for the confounder staff member, the medical history is only significant shorter for gynaecologist 2 (MD 02m40s, 95% CI 0:00:58 – 0:04:23, p=0.003) in the DAA+ group. The time needed for explanation is no longer significantly different after correction for the confounder operation. The totality of the medical history is significantly less in the DAA- group regarding scores on the domains defecation (p=0.010), overactive bladder (p=0.010) and sexuality (p=0.000).
The overall experience of participating patients of both research groups regarding the appointment is positive. However 29% of the patients experienced no additional value of the DAA and 20% questions its value. Twenty-nine percent of the patients who completed the DAA find that it contains unnecessary questions, such as questions that do not apply to the patient.
Conclusion.
The DAA increases the efficiency of a consultation and contributes to a complete medical history. Staff members are positive regarding the DAA, however attention to improve patient satisfaction is needed. To improve this the DAA has to be integrated in such way that patients believe it’s an important contribution to their care.

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Euthanasie en dementie: het perspectief van patiënt en arts.

The Netherlands legalized voluntary active euthanasia (VAE) in 2002, after about thirty years of public debate. Since then, Dutch physicians are no longer persecuted when carrying out VAE on patients within specific legal boundaries. Nevertheless, VAE remains subject of ongoing debate, especially considering patients with psychiatric disorders or dementia. However, the perspective of patients with dementia and that of nursing home physicians remains underexposed. The current study aims to scientifically approach these both perspectives.
A qualitative study was performed, consisting of 8 interviews with patients, in which they discussed their views on end of life and VAE, from the project ‘Help demented! Patient and caregiver speak out’. In addition, 12 interviews were performed with nursing home physicians.
Patients with dementia are mostly pessimistic about their distant future. Some of them intend to request VAE at some point in time. The contemporary practice considering VAE in the Netherlands is, however, not commonly known among participants.
Participating nursing home physicians do not carry out euthanasia on patients living in nursing homes. Most frequently used motives are lack of competency and lack of communication abilities in these patients. Also, participants declare that they do not (or would not) carry out euthanasia in the presence of an advance directive on VAE, because patients can change their mind over the course of their illness.
In contrast, nursing home physicians do take into account advance directives on VAE when making decisions about withdrawing potentially life sustaining treatments, together with assessments on quality of life and patient suffering. However, these latter concepts remain ill-defined.
Nursing home physicians make a distinction between VAE and the withdrawal of potentially life sustaining treatments. The distinction was found to be related to the difference in psychological impact between these decisions on the physician. Application of concepts such as substituted judgment based on the presumed wishes of the patient, quality of life, and suffering remains inadequate. Presumably, decisions concerning end of life are best justified by a more objective model of patient’s best interest. Such needs to be developed.

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Immunohistochemical MYC protein expression in the different histological grades of follicular lymphoma.

Background:
Follicular lymphoma (FL) is the second most occurring Non-Hodgkin lymphoma. FL is subdivided into the different histological grades 1 – 3B. Normally the course
of FL is indolent but sometimes it may undergo transformation into a more aggressive type of lymphoma (tFL). Amongst other genes, MYC alterations may play an important role in this transformation. Until recently, MYC alterations could only be detected with the expensive techniques of karyotyping or FISH. A reliable commercial antibody came available that can detect MYC protein expression with the cheaper and easier to perform technique of immunohistochemistry (IHC).
Objective:
We wanted to determine if MYC-IHC was suitable to analyse FL and if there was
a difference in MYC protein expression in the different grades of FL as well as before and
after transformation. Besides that we wanted to assess its potential clinical value by analysing survival after dichotomisation of MYC-IHC expression scores.
Materials & methods:
Patients were selected from the database of the Haematology department of the UMCG were divided into 4 cohorts according to their histological grade; IHC was performed for MYC protein expression. If possible, paired cases before and after transformation were included. Stained slides were digitalised and quantification of expression was done with the grid-point method. 5 representative areas were selected and a grid was projected over each area. On the intersections of these grids, nuclear staining was scored positive or negative. Slides with Bukitt lymphoma and benign tonsils were included as controls.
Results:
All included samples were suitable for quantification and a standard error <2% was
reached for all samples. In total 111 samples of FL or tFL were included in this study. Fortysix cases of FL grade 1/2 without transformation had a median expression score of 4.0%, 11 cases of FL grade 3A had a median expression score of 14.0%, and 4 cases of FL grade 3B had a median expression score of 26.5%. In addition 21 paired cases of FL ! and tFL were
included as well as 8 tFL without its prior indolent FL. Median expression in the paired cases was 6.0% before transformation and 54.0% after transformation. Expression of FL 1/2 was significantly lower than in FL 3A/B (P=0.002) and expression in FL 3A/B was significantly lower than in tFL (P=0.002). FL 1/2 with transformation had significant higher expression than FL 1/2 without transformation (P=0.03). After dichotomisation, MYC-IHC appeared an
indicator for survival in FL 1/2 but not in tFL.
Conclusion:
This study shows that MYC-IHC can be reliably performed and rises significantly with each grade of disease. This may represent a further step in understanding the pathogenesis of FL and transformation. Overall survival is influenced by MYC-IHC score in FL grade 1/2. More clinical significance can be obtained by future research where the results will be validated with FISH.

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Adenocarcinoma of the Esophagogastric Junction: Staging and Surgical Treatment.

Introduction
The aim of this study was to evaluate the outcome of surgical therapy and the accuracy of preoperative endoscopy, endoscopic ultrasonography (EUS) and CT-scanning on staging and tumor localization. Furthermore, the different surgical approaches were evaluated with regard to postoperative outcomes and survival.
Method
A prospective single center database of 266 patients was used of all patients with surgically resectable esophageal and gastric carcinomas from 2003 until present. All upper gastro-intestinal endoscopy, endoscopic ultrasound and histopathological reports were reviewed and patients were classified according the Siewert classification (I-III). Treatment was based on pre-operative imaging as well as intra-operative tumor localization. Either an esophagus-cardia resection or an extended total gastrectomy was performed. Histopathological analysis, considered as gold standard, was compared with the preoperative findings.
Results
The overall accuracy for endoscopy/EUS and CT scan in determining the tumor localization according to the Siewert classification was 73% and 61% respectively. The main reason for this low accuracy was due to the high amount of patients that were preoperatively classified as a type I tumor, whereas the pathology report showed a type II tumor. The overall accuracy for determining a positive nodal station was 77% for EUS and 71% for CT. The accuracy was high, 80 – 92%, for the upper thoracic lymph nodes and decreased to 50 – 80% for the peritumoral and abdominal lymph nodes.
Overall 5-year survival improved with esophagectomy on univariable analysis in patients with a type II tumor (p = 0.026). However, the overall morbidity was significantly higher in the esophagectomy group (p = 0.028), due to a higher amount of pneumonia (47% versus 25%; p = 0.015). In patients with a Siewert type II tumor, high thoracic nodal involvement was present in 10% of the cases. In patients who received a transthoracic or transhiatal esophagectomy, lymph node metastases in the para-esophageal nodes was found in respectively 32% and 36% of the cases, whereas in patients who received a gastrectomy, in only 5% of the patients the para-esophageal nodes contained metastases.
Conclusion
The application of endoscopy/EUS and CT in determining the tumor localization according to the classification described by Siewert is of limited value. EUS seems to be superior than CT in determining the nodal status. It can accurately predict nodal involvement of the high thoracic lymph nodes, however it tends to understage with peritumoral and abdominal nodal stations. Our data suggest to perform an esophagectomy in patients with a type II tumor. Further research, preferably a prospectively randomized controlled trail, needs to be conducted to confirm these findings.

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The role of O-GlcNAcylation in trophoblast and its contribution to placental dysfunction

The role of O-GlcNAcylation in trophoblast and its contribution to hyperglycemia-induced placental dysfunction
The prevalence of gestational diabetes mellitus and obesity during pregnancy keeps increasing. Gestational diabetes mellitus creates a hyperglycemic intrauterine environment, which increases flux through the hexosamine biosynthesis pathway. This is expected to enhance protein O-GlcNAcylation in trophoblast. We hypothesise that in turn this may contribute to placental dysfunction and predisposition to chronic conditions including obesity, diabetes mellitus, cancer and cardiovascular diseases. In this project we aim to investigate the O-GlcNAcylation of Specific protein 1 (Sp1), a known O-GlcNAcylated protein present in trophoblast, and the effect of O-GlcNAcylation on trophoblast function.
BeWo cells were treated with a specific substrate of the hexosamine biosynthesis pathway, D-glucosamine at a range of doses (0-5.0mM) for time points up to 48 hours to investigate whether Sp1 is O-GlcNAcylated in trophoblast. This was monitored by immunofluorescence staining and Western blotting. The influence of altered O-GlcNAcylation levels on cell proliferation was researched by analyzing total cell number after glucosamine treatments (0-10mM) for 24 and 48 hours. To see whether this effect was lasting BeWo cells were treated with glucosamine (0, 2.5m and 5.0mM) for 24 or 48 hours, and then changed back to non-glucosamine containing medium. The effect was monitored by counting total cell number, using the hemocytometer, directly after the medium change, and at 24 and 48hours after the medium change. Finally we looked at the influence of glucosamine treatments on leptin production in BeWo cells by performing a leptin ELISA on cell culture supernatant of glucosamine treated (0-2.5mM) BeWo cells was collected at 72 hours.
Results show that O-GlcNAc modification occurs within in the placenta. No substantial evidence is found that specific protein is O-GlcNAcylated, however abundance seems to increase with increasing glucosamine treatments. Cell proliferation is significantly decreased with increasing glucosamine treatments (P<0.0001). However, the cells seem to be able to recover from glucosamine treatments even if harsh and for a longer time of exposure since differences in total cell number where no longer significant. Finally leptin production has shown to decrease with increasing glucosamine treatments (P=0.0258).
O-GlcNacylation is an abundant modification in the placenta, which potentially affects Sp1 abundance and functioning. Also it has an effect on trophoblast functions like proliferation, survival and leptin production. These alterations may be involved in inducing placental dysfunction or inducing a predisposition to chronic disease, therefore it is important to further investigate these matters to get better insight on the mechanism behind this phenomenon.

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Het effect van barbotage bij tendinitis calcarea.

Introduction
Needle aspiration of calcific deposits (NACD) is the treatment of choice for calcific tendinitis (CT) that does not respond well to conservative treatment. NACD is effective in approximately 70-75% of the patients. Multiple treatments are often necessary to obtain permanent results. Factors associated with treatment failure or the need for multiple treatments are unknown. In a retrospective cohort study we investigated variables associated with treatment failure and the need for multiple treatments.
Methods
In the period from January 2010 till June 2013, 431 consecutive patients (277 female, 154 male; average age 51,4 years) with symptomatic CT treated by NACD were included. A dichotomous symptom scale (symptom-free or not symptom-free) was used to analyze results at six months post-intervention. Logistic regression analysis was used for identifying factors associated with treatment failure and the need for multiple treatments.
Results
At six months post intervention 73,5% of patients were free of symptoms. Not achieving a NRS score <3 two weeks post-intervention (OR 2,58; p=0,001) and being referred by an orthopedic surgeon (OR 3,63; p<0,001) were associated with treatment failure. Higher NRS scores at two weeks post-intervention were associated with multiple treatments (OR 1,16; p=0,004).
Conclusion
NACD is an effective treatment for CT in 74% of patients. The factors associated with failure of treatment and the need for multiple treatments have only limited clinical value. Therefore, this study does not offer a good explanation for treatment failure or the need for multiple treatments. However, this study shows that partial rotator cuff tears do not affect the outcome of NACD. Accordingly, NACD is an effective treatment for patients with CT and concomitant partial rotator cuff tears. Based on this study we suggest to consider a second NACD procedure in case of persistent complaints and to postpone surgical interventions for as long as possible.

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Kwaliteit van invullen van aanvraagformulieren voor urinekweken na een nascholing voor huisartsen en doktersassistenten.

In the city of Zwolle and the surrounding area medical specialists from Isala hospital and general practitioners work together to develop local consensus guidelines. These guidelines are meant to ensure that cooperation between primary and secondary care is improved. One of these guidelines teaches GP’s how to properly fill out request forms for urinary cultures. Along with the guideline the GP’s have the opportunity to attend an education session which is an interactive course that focuses on how to fill out request forms for urinary cultures. Besides the Interline course the physician assistants are offered an education session which also focuses on filling out request forms for urinary cultures.
The effect of the education sessions on the filling out of test forms for urinary culture was studied in 30 GP’s offices, on the short and the long term.
The research suggested that if the GP’s as well as the physician assistants receive the education sessions, the quality of filling out test forms for urinary cultures is improved significantly. This effect was not observed in the group with GP’s offices where no one received an education session.

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Spoedechografie in combinatie met non-invasieve cardiac output monitoring (NICOM®) als voorspellers van de volumerespons.

Background:
Sepsis is a frequently diagnosed disease in the emergency department with a high mortality rate up to 50%. The treatment of sepsis is generally based on fluid resuscitation, which only half of the treatment population responds to. In order to give the patient the right treatment, a fast and non-invasive method to predict fluid responsiveness would be of great interest.
Objective:
In this paper, we describe a trial investigating whether the respiratory variation in diameter of the vena cava inferior can be used as fluid responsiveness indicators. Furthermore, we investigate whether attributive sonography of the heart and lungs is a viable technique for fluid therapy guidance.
Methods:
During a trial period of 19 weeks all patients admitted to the emergency department were screened for sepsis and included if they were treated with at least 500 mL, 0,9% NaCl. Before fluid therapy, sonography (Zonare) was used to determine the caval index, to assess the contractility of the heart, and to screen the lungs for the presence of B-lines. The cardiac output and stroke volume was monitored before and after fluid therapy (NICOM Cheetah RELIANT). A positive response on fluid therapy was defined as an increase in stroke volume or cardiac output of at least 10%. Based on this definition, patients were divided into two groups; responders and non-responders.
Results:
A total of 37 patients with sepsis were included, of which 46% were responders. Results showed that the caval index was not reliable for predicting the response to fluid therapy. However, we observed a remarkable decrease in arterial pressure for all subjects. This behavior is most likely due to the increase in vasodilatation during the initial phase of sepsis, or loss of the initial stress response after being admitted to the emergency department. We hypothesise that the adequate treatment of sepsis includes treatment volumes of more than 1000mL, 0,9% NaCl. These treatment volumes were not associated with the development of additional complications.
Conclusion:
Based on the findings of this study, the caval index was found not to be viable as a fluid response predictor for patients with sepis. Furthermore, assessment of the global contractility of the left ventricle was not attributive for fluid therapy guidance.

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Sinusoidal high intensity exercise training in COPD patients with ventilatory limitation.

Pulmonary rehabilitation (PR) is an effective treatment in Chronic Obstructive Pulmonary Disease (COPD) patients. Although high intensity training can improve exercise capacity in COPD patients more than lower intensity training, training intensity is often restricted due to ventilatory limitation.
Recently, it has been shown that COPD patients are able to exercise on a high-intensity rapid sinusoidal work rate (SW) reaching 120% of incremental peak work rate (PWR) on a cardiopulmonary exercise test (CPET) without reaching ventilatory limitation. We therefore investigated whether this training protocol resulted in a larger training effect at work rate 6 minutes (WR6) than the traditional constant work rate (CWR) training.
In this study, 7 CWR (age, 62.7 ± 8.7 years; forced expiratory volume in the first second (FEV1), 44.0 ± 19% of predicted) and 6 SW subjects (age, 70.2 ± 8.1 years; FEV1, 50.6 ± 21% of predicted) underwent pulmonary function test and CPET. Subjects reached at least 40 watts during CPET and were all ventilatory limited. 4 CWR tests were performed to obtain the critical power (CP), the power defined as the maximal work rate that can be maintained for at least 20 minutes. Quadriceps muscle strength was measured by 1RM. Subsequently, subjects were randomized between SW or CWR training and underwent a 4 week exercise training program. After the last training, initial exercise tests and 1RM were repeated.
Exercise training in both groups resulted in a greater increase of exercise endurance at WR6. PWR increased by 4 watts to 86 watts (CWR) and 3.7 W to 81 W (SW). CP increased from 51.4 to 58.2 W (p<0.05) CWR and from 44.1 to 48.9 W (p=0.116) SW. in both groups, 1RM increased significantly from 275 to 305 lbs (CWR) and from 306 to 341 lbs (SW). No significant differences were found between the groups. These results emphasize the benefits of high intensity exercise training on exercise capacity. No benefits were seen in favor of SW training or CWR, possibly explained by the power of the study (preliminary data).

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Patiënten met Chronische Idiopatische Axonale Polyneuropathie: beoordeling van de balans.

Objective:
Patients with Chronic Idiopathic Axonal Polyneuropathy (CIAP) often report balance impairment. However, in earlier research patients with CIAP achieved the maximal scores on the Berg Balance Scale (BBS). Balance problems in patients with CIAP are caused by both sensory distortions and loss of muscle strength, , but as the muscle weakness in CIAP is often relative small, and patients often complain of balance problems in situations were visual control is impaired, sensory ataxia seems to be the main cause of it. The visual system is excluded in only one item of the BBS. The objective of this study is to examine whether extending the BBS with four additional items (BBSplus), in which the visual system is excluded, will lead to a better representation of balance problems in patients with CIAP. In addition this study will look at the relationship between scores on the BBsplus and variables of function and activity. In addition this study assesses whether the BBSplus can be used to follow deterioration of balance in time.
Research design and methods:
This study was an extension within a prospective longitudinal observational study in 92 newly diagnosed CIAP patients. Physical function was measured (using maximal isometric muscle strength, sensory functioning, Shuttle Walk Test (SWT), BBS, BBSplus, and physical activity), and patients were asked to complete a questionnaire (Rand-36) for four times in four years. The Modified Rankin Score (MRS) and the existence of ‘experienced balance problems’ were determined. This variable was used as the golden standard. Data was statistical analysed using crosstabs, tests for correlation, and dependent t-tests (or a wilocoxon signed ranktest) using SPSS.
Results:
Ceiling effects disappear by using the BBSplus (1.1%) instead of the BBS (34.8%). Sensitivity increases (BBSplus 21.3%, BBS 6.4%), and specificity remains the same (both 86.4%). The BBSplus has good internal consistency, cronbach’s alpha 0.95. A strong positive correlation (Rho 0.491 (p<0,5) exists between muscle strength and BBSplus score. The positive correlation between sensory functioning, and BBSplus score is weaker (Rho 0.296 (p.<.00). The other tests also showed significant correlations. In four years, patients show a significant decline in BBSscore and other variables tested.
Conclusion:
The BBSplus gives a better representation of the balance problems in patients with CIAP. Ceiling effects disappear, sensitivity incraeses and specificity remains the same. BBSplus score has a stronger correlation with muscle strength compared with loss of sensory functioning. Therefore this study cannot confirm the hypothesis that sensory ataxia is the main cause of balance impairment. Deterioration of the BBSplus score in time can be seen. Further research, with a better golden standard for balance, should determine whether the BBSplus can monitor an actual decline in balance. Further research is necessary to confirm the BBSplus as a valid instrument for balance in patients with CIAP and normative values must be obtained in the future.

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Langetermijngevolgen van de behandeling van borstkanker: de relatie tussen vermoeidheid en depressie.

Aim:
The aim of this research is to assess the relationship between fatigue en depression on the long term in women who have been treated for breast cancer in an unselected population in primary care. The effect of chemo- and/or radiotherapy on this relationship will also be taken into account.
Material and Methods:
From a population of nearly 36.500 patients, 81 patients with breast cancer and 51 controls without cancer were selected. All patients with breast cancer have been treated after 1970, were younger than 80 years at time of diagnosis, and have had treatment for breast cancer at least five years ago. From the 81 patients with breast cancer 49 have been treated with chemo- and/or radiotherapy, 32 patients were only treated with radiotherapy. The Hospital Anxiety and Depression scale (HADS) and the Multidimensional Fatigue Inventory (MFI-20) were used to assess fatigue and depressive symptoms in patients and controls. Patients who have been treated with chemotherapy and/ or radiotherapy haven been compared within the patient population and with controls by means of the Generalized Linear Model (GLM).
Results:
After a median follow-up of nine and a half years there was a significant relationship between fatigue and depression (p<.001). A non-significant patient proportion had an increased score of the MFI-20 and the HADS in comparison with the controls. One point increase of the HADS meant for the chemotherapy group a higher score of the MFI-20 (B:2.2; 95% CI:-2.0-2.8) than in comparison with the radiotherapy group (B:0.9; 95% CI:-5.0-6.8). Literature also shows that there is a relationship between fatigue and depression, it is not clear if type of therapy has an influence on this relationship. Literature displays that a significant part of women who have had breast cancer experience complaints of fatigue and depression for years after treatment. Women treated with chemotherapy seem to be more fatigued in comparison with women who have not been treated with chemotherapy for breast cancer.
Conclusion:
There is a relationship between fatigue and depression in breast cancer survivors on the long term. This is in accordance with literature research. Chemo- and radiotherapy do not have a significant influence on this relationship. This study shows that a non-significant greater proportion of patients have an increased score at the MFI-20 and HADS in comparison with the controls. Literature shows that a small significant part of women who have had breast cancer keeps suffering from fatigue and depression on the long term. This study further shows that in comparison with patients who are only treated with radiotherapy, patients treated with chemotherapy have a higher score at the MFI-20 when the HADS increases with one point. This relationship however doesn’t differ significantly. Literature shows that women treated with chemotherapy seem to be more fatigued in comparison with women who have not been treated with chemotherapy for breast cancer.

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Airstacken bij myotone dystrofie. De effecten van een preventieve techniek op een uitdagende patiëntengroep en hun mantelzorgers.

Introduction:
Respiratory complications are the primary cause of mortality in patients with myotonic dystrophy (MD). The purpose of this study was to investigate an intervention to prevent these complications. This intervention, called air stacking (AS), is a lung volume recruitment technique that is used for cough augmentation. Secondary aims of this study were compliance to AS and the importance of (family) caregivers in this process.
Method:
An explorative pilotstudy. Inclusion criteria: patients with known myotonic dystrophy, practicing AS >9 months, recruited out of medical files at the neurology department of the Medical Centre Leeuwarden, RadboudUMC, Rehabilitation Friesland, the Centre of Domiciliary ventilation of Groningen and Maastricht. By researching medical files the respiratory complications before starting AS and after starting AS were counted. Questionnaires were used concerning compliance to AS. The view of caregivers was also taken into account.
Results:
17 patients with MD type 1 were included, 14 of these had a (family) caregiver. The median quantity of respiratory complications 1 year before starting AS was 1,0 per year. 1 Year after starting AS, this declined significantly (p=0,009) to 0,0 per year. Two years after starting AS a significant decrease remained, p=0,010. Three years after starting AS this decrease was not significant anymore. 9 Of 15 patients had low rates of adherence to AS, which showed a tendency towards a negative influence on the effectiveness of AS, however this was insignificant. 15 Of 17 patients required motivational or physical support in applying AS.
Conclusion:
This study shows that AS reduces the number of respiratory complications significantly in the first 2 years after starting AS and that compliance and motivation are important in applying AS in MD patients. A tendency towards a negative influence of a low rate of adherence to the effectiveness of AS was shown, however insignificant. MD patients can rarely apply AS without help, as the majority requires motivational or physical support.

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