How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis.

BACKGROUND: Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient. AIM: To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. METHODS: Eligible patients (n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning (n = 102) or BD with one 2 g sachet in the morning and one in the evening (n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. RESULTS: The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval -3.4, 24.1; P = 0.14). Improvement of UC-DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing. CONCLUSIONS: When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789).

Mild colonic diverticulitis can be treated without antibiotics. A case-control study.

AIM: Conservative treatment of mild colonic diverticulitis usually consists of observation, restriction of oral intake, intravenous fluids and antibiotics. The beneficiary effect of antibiotics remains unclear. The aim of this study is to evaluate the need for antibiotics in mild colonic diverticulitis. METHOD: A retrospective case-control study was performed in 272 patients with mild colonic diverticulitis admitted to two hospitals with distinctly different treatment regimes concerning antibiotic use. RESULTS: A total of 191 patients were treated without antibiotics and 81 with antibiotics. Groups were comparable at baseline with respect to age, sex, comorbidity, and use of nonsteroid anti-inflammatory drugs, steroids and aspirin. All patients had imaging-confirmed diverticulitis. C reactive protein and white blood count levels did not differ significantly. In the antibiotics group there were significantly more patients with a temperature of 38.5°C or higher on admission. (8 vs 19%; P=0.014). Treatment failure did not differ between groups (4 vs 6%; P=0.350). The risk of recurrence was higher in the antibiotics group on logistic regression analysis but did not reach statistical significance (odds ratio, 2.04; confidence interval, 0.88-4.75; P=0.880). The only factor that increased the risk of recurrence was nonsteroid anti-inflammatory drug use (odds ratio, 7.25; confidence interval, 1.22-46.88; P=0.037). CONCLUSION: Antibiotics can be omitted in selected patients with mild colonic diverticulitis and should be given on indication only.

Management of diverticulitis: results of a survey among gastroenterologists and surgeons.

AIM: The study aimed to investigate current management strategies for left-sided diverticulitis and compare them with current international guidelines. Differences between surgeons and gastroenterologists and between gastrointestinal and nongastrointestinal surgeons were assessed. METHOD: A web-based survey of treatment options for uncomplicated and complicated diverticulitis was carried out among surgeons and gastroenterologists in the Netherlands. Only surgeons were asked about surgical strategy. RESULTS: A total of 292 surgeons and 87 gastroenterologists responded, representing 92% of all surgical and 46% of all gastroenterology departments. Ninety per cent of respondents treated mild diverticulitis without antibiotics. About one-fifth (18% gastroenterologists; 19% surgeons) regarded a CT scan as mandatory in the initial assessment. Most surgeons and gastroenterologists used some form of bowel rest, would consider outpatient treatment and would perform a colonoscopy on follow up. For Hinchey Stage 3, 78% of surgeons would consider resection and primary anastomosis and laparoscopic lavage was viewed as a valid alternative by 30% of gastrointestinal and 2% of nongastrointestinal surgeons. For Hinchey stage 4, 46% of gastrointestinal and 72% of nongastrointestinal surgeons would always perform Hartmann's procedure. CONCLUSION: The treatment of diverticulitis in the Netherlands shows major differences when compared with guidelines for all stages of disease.

Harmonisation of TB control in the WHO European region: the history of the Wolfheze Workshops.

In 1990 a workshop was organised in the village of Wolfheze (the Netherlands), where experts discussed the critical interventions that would foster elimination of TB in Europe. This event has been followed by several more over the following two decades to become known as the "Wolfheze Workshops". This article provides a brief overview of the history and the impact the Wolfheze Workshops have had on the commitment of European governments to standardise definitions, recording and reporting systems and, thus, permitted comparison of interventions and improving TB control across borders. The Wolfheze Workshops have been and still are an essential platform for this exchange of experiences, promoting common approaches.

Diagnosis and treatment of tuberculosis in undocumented migrants in low- or intermediate-incidence countries.

SETTING: Countries with low or intermediate tuberculosis (TB) incidence. OBJECTIVES: 1) To gather information on individuals and TB patients who are undocumented migrants and their access to TB diagnostic and treatment services; 2)to discuss interventions to strengthen diagnosis and treatment and 3) to formulate recommendations on how to ensure adequate TB prevention and control. DESIGN: Questionnaires sent to members of the Working Group (WG) on Transborder Migration and TB, managers of national TB programmes and EuroTB correspondents; literature research and development of a paper by a writing committee through consultation. RESULTS: Undocumented migrants represent 5-30% of immigrants and 5-10% of TB cases. Most countries reported full access to diagnosis and treatment, but in practice there were limitations. Most countries also reported that they could and did deport cases who were on TB treatment. A variety of activities to ensure access were reported from different countries. CONCLUSION: The WG recommends that 1) health authorities and/or health staff should ensure easy access to low-threshold facilities where undocumented migrants who are TB suspects can be diagnosed and treated without giving their names and without fear of being reported to the police or migration officials. Health authorities should remind health staff that they have an obligation of confidentiality; 2) each country should ensure that undocumented migrants with TB are not deported until completion of treatment; and 3) authorities and non-governmental sectors should raise awareness among undocumented migrants about TB, emphasising that diagnosis and treatment should be free of charge and wholly independent of migratory status.

[Large-scale outbreak investigation for tuberculosis in Zeist]. / Grootschalig contactonderzoek op tuberculose in Zeist.

Recently a large-scale outbreak investigation was held among customers of a supermarket in the Dutch town of Zeist after an employee was diagnosed with smear-positive pulmonary tuberculosis. About 14,000 people had a tuberculin skin test and an additional 6,000 had a chest X-ray. About 400 positive skin tests and 8 cases of active tuberculosis have been reported so far. Investigation of contacts of infectious tuberculosis cases is an important tool in tuberculosis control in low-prevalence countries. It includes chest X-ray examination for active pulmonary tuberculosis after or instead of tuberculin skin testing, and identifying contacts with latent tuberculosis infection followed by preventive treatment. Investigation of household and other close contacts is highly effective. This may not be true for sporadic contacts who are likely to have a low risk of infection, such as in this investigation, where the prevalence of recent infections estimated from reported data is only 3%. The benefits of detecting these cases must be weighed against the costs of such large-scale operations and the probability of false-positive skin test results.

Serum matrix metalloproteinase MMP-2 and MMP-9 in the late phase of ischemia and reperfusion injury in human orthotopic liver transplantation.

INTRODUCTION: Ischemia and reperfusion (I/R) injury during orthotopic liver transplantation (OLT) is accompanied by neutrophil infiltration and degradation of extracellular matrix. Matrix metalloproteinases (MMP) play an important role in the turnover of extracellular matrix components. We assessed the changes in level and composition of serum MMP-2 and MMP-9 in relation with I/R injury after human OLT. METHODS: Thirty-three patients were separated into two groups according to their peak level of aspartate aminotransferase (AST) after OLT (AST < 1500 IU/L: n = 22; AST > 1500 IU/L: n = 11). Serum MMP-2 and MMP-9 were measured before transplantation as well as 2 days and 1 week after OLT using ELISA (MMP protein) and BIA (enzymatic activity of MMP). RESULTS: MMP-2 and MMP-9 protein concentrations were comparable before and 2 days after OLT, whereas at 1 week MMP-2 decreased and MMP-9 increased significantly. However, there were no significant differences between patients with high or low peak AST at all time points. Also, the composition of MMP-2 and MMP-9 did not differ over time between the groups of patients. CONCLUSION: Serum MMP-2 and MMP-9 do not relate to the late phase of hepatic I/R injury after human OLT.

[Centenary of the Royal Dutch Central Association for the Prevention of Tuberculosis]. / Honderd jaar Koninklijke Nederlandse Centrale Vereniging tot bestrijding der tuberculose (KNCV).

The Royal Dutch Tuberculosis Association (Koninklijke Nederlandse Centrale Vereniging tot bestrijding der Tuberculose (KNCV)) was founded in 1903. Since then various interventions against tuberculosis have been introduced on the basis of medical and technological opportunities and in response to the epidemiological situation. The introduction of effective drugs during the 1940s and 1950s was by far the most important development and led to a sharp decline in the annual rate of infection and to the disappearance of tuberculosis as a common disease. Following the appointment of the independent National Policy Committee for Tuberculosis Control, Royal Dutch Tuberculosis Association could concentrate on its innovating tasks: the development of new interventions based on epidemiological data and scientific research.

99mTc-MAG3 diuretic renography in children: a comparison between F0 and F+20.

The aim of this work was to compare the quality of renal drainage obtained with two well-described procedures of diuretic renography (F+20 and F0 tests). We selected 36 clinically stable children, aged 10 days to 17 years, with unilateral (25) or bilateral (11) hydronephrosis, in whom both F+20 and F0 tests were successively performed. In all cases, a late image (PM) was acquired after micturition and after changing the position of the patient. The following parameters were calculated: the time to the maximum of the basic renogram (Tmax); and the normalized residual activity (NORA) and output efficiency (OE) at the end of the 20 min renogram, at the end of the furosemide test (35 min) and on the PM image. In F+20, the renal drainage was better on the PM image than at the end of the diuretic renogram, whereas, in F0, the renal drainage was better on the PM image than at the end of the 20 min diuretic renogram. When comparing F0 and F+20, both OE and NORA parameters revealed slightly better drainage at the end of the 20 min F0 renogram than at the end of the 35 min F+20 diuretic renogram. The drainage obtained on the late post-voiding image was comparable for both F0 and F+20 tests. In conclusion, the quality of drainage obtained during the F+20 and F0 procedures can easily be compared using both OE and NORA. A very similar quality of drainage was reached for both procedures when considering only the PM image. This PM view remains mandatory irrespective of the timing of the furosemide injection and despite the use of tracers with a high extraction rate.

Calculation of renal retention function without deconvolution.

The aim of this study was to evaluate Rutland's method for the recovery of renal retention function without deconvolution. Renograms (n=5800) were generated by convolving 10 real input functions with 580 artificially created retention functions. Their ratios of minimal to mean transit time ranged from 0.1 to 1.0, and for mean transit time ranged from 3 to 60 min. The retention function was recovered from each renogram and its associated input function by calculating the first derivative of the residence time of the tracer in the kidney. Minimal, mean, and maximal transit time of the recovered retention function were calculated and compared with the original values. Qualitatively, the recovered retention function differed little from the original one. Quantitatively, values for recovered minimal transit time equalled original minimal transit time in all cases, whilst recovered mean transit time and maximal transit time equalled, respectively, the original mean transit time and maximal transit time if the original minimal to mean transit time ratio equalled 1. If this ratio was less than 1, recovered mean transit time was higher than original mean transit time and recovered maximal transit time was lower than original maximal transit time. For values of mean and maximal transit time, the differences from the original value increased with increasing original mean and maximal transit time, respectively, and with increasing renal clearance and decreasing minimal to mean transit time ratio. It is confirmed that Rutland's method is a particularly interesting alternative to deconvolution analysis. The errors that occur when recovering the retention function are relatively small.

Is deconvolution applicable to renography?

The feasibility of deconvolution depends on many factors, but the technique cannot provide accurate results if the maximal transit time (MaxTT) is longer than the duration of the acquisition. This study evaluated whether, on the basis of a 20 min renogram, it is possible to predict in which cases the MaxTT will exceed 20 min. Renograms of various shapes were simulated by convolution of a plasma disappearance curve and various created retention functions with a mean transit time (MTT) ranging from 3 to 23 min. The values of MaxTT were then derived from the created curves and compared to three parameters of transit measured on the renograms: the time to reach the maximum of the curve (Tmax), the output efficiency at 20 min (OE20), and the normalized residual activity at 20 min (NORA20). The proportion of retention functions (n=390) with MaxTT>20 min increased with increasing Tmax (e.g. 9% for 6< or =Tmax<10 min, and 34% for 11< or =Tmax<15 min), increasing NORA20 (e.g. 20% for 1.4< or =NORA20<3.0, and 84% for 3.0< or =NORA20<5.0) and decreasing OE20 (19% for 50%

Motor and sensory function of the rectum in different subtypes of constipation.

BACKGROUND: It is not known whether evaluation of motor and sensory function of the rectum using a barostat may help to distinguish subtypes of constipation. METHODS: Motor and sensory function of the rectum have been evaluated using a barostat in 14 patients with slow transit constipation (STC), 12 patients with constipation-predominant irritable bowel syndrome (IBS) and 18 healthy controls. First minimal distending pressure was determined, after which spontaneous adaptive relaxation of the rectum was monitored. Then a step-wise isobaric distension procedure was performed, during which symptom perception was determined. The distension was followed by a 90-min barostat procedure: for 30 min in the basal state followed by ingestion of a semi-liquid meal (postprandial state). RESULTS: Minimal distending pressure was not different between both patient groups and controls, neither was compliance different between constipated patients and controls. The degree of spontaneous adaptive relaxation was in the same range in all groups. During distensions with high pressures, the perception of urge was significantly reduced in STC patients compared to IBS and controls, while the perception of pain was significantly increased in IBS versus STC and controls. Postprandially, a small decrease of rectal volume was only observed in the control group, but not in the patients. CONCLUSIONS: Rectal motor characteristics are not different between patients with constipation-predominant IBS, patients with STC and healthy controls while during isobaric distensions, sensations of urge were reduced in STC and sensations of pain were increased in IBS. Rectal visceroperception testing may help distinguish groups of patients with different subtypes of constipation.

European Medical Device Directive: impact on nuclear medicine.

The European Council Directive 93/42/EEC concerning medical devices (14 June 1993) assigns new responsibilities and imposes technical requirements both to the manufacturer and user of medical devices. In this paper the general outlines of the directive are discussed with a particular emphasis on the risk classification of products, the compliance and evaluation process and the CE-marking regulations. Furthermore, some practical implications are highlighted for devices and tools relevant to the field of nuclear medicine such as radiation detectors, gamma- and PET-cameras and software.

A survey of guidelines in 27 EANM associated societies by the EANM Task Group on Quality Assurance and Standardisation. European Association of Nuclear Medicine.

The main aim of the EANM Task Group on Quality Assurance and Standardisation is to develop harmonised clinical procedures that are accepted within Europe. In order to achieve an evidence-based analysis of guidelines in the 27 EANM member societies, a survey was conducted. A questionnaire in mid 1999 investigated three major questions: (1) current status of national guidelines in EANM member societies, (2) specification of the cover and level of these national guidelines, and (3) future desires for national, EANM and SNM guidelines. The complete response rate was 96% (26/27). Guidelines are required by 19 of 27 member societies and have been initiated by 16 member societies. Guidelines are provided by 13 member societies, generally in the national language. In ten societies, specialists other than nuclear medicine physicians, mostly physicists and radiopharmacists, take the lead on some guidelines. Moreover, in some national societies there is active collaboration with other medical societies when writing guidelines, particularly cardiology societies. Currently, only 18% of the necessary procedure guidelines are covered. Compared with a survey conducted in 1993 by the EANM Committee on Quality Assurance and Standardisation, slow progress has been made in this regard, but compared with a survey conducted by the same committee in 1996 in 23 EANM member societies, the number of member societies providing guidelines has approximately doubled. Moreover, 26 of 27 member societies share a commitment for future development of guidelines and 21 of 27 prefer EANM guidelines to national guidelines. The results of this questionnaire justify the need for close co-operation between EANM, EANM member societies, the EANM Task Group on "Quality Assurance and Standardisation" and the Guideline Committee of the SNM. The clinical priorities are considered to be cardiac, renal and brain procedures.