A standardised approach towards PROving the efficacy of foods and food constituents for health CLAIMs (PROCLAIM): providing guidance

Diet is well known to have beneficial health properties that extend beyond traditionally accepted nutritional effects. The approach involved in elucidating these beneficial physiological effects is becoming more important, as reflected by increasing research being undertaken. With growing consumer awareness of foods and food constituents and their relationship to health, the key questions for regulators, scientists and the food industry continue to relate to: (1) how consumers could be protected and have confidence that the health claims on foods are well supported by the evidence; (2) how research on physiological effects of food (constituents) and their health benefits could be stimulated and supported; (3) how research findings could be used in the development of innovative new food products. The objectives of this paper are to provide a set of recommendations on the substantiation of health claims for foods, to develop further guidance on the choice of validated markers (or marker patterns) and what effects are considered to be beneficial to the health of the general public (or specific target groups). Finally, the case for developing a standardised approach for assessing the totality of the available scientific data and weighing the evidence is proposed.     

Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About one third (35 %) of the Turkish/Moroccan patients fulfilled criteria for breast cancer genetic counseling, compared to 21 % of the comparative group (P = 0.001); this was largely due to a relatively young age at diagnosis in the migrant group (26 % <40 years vs 5 % in the comparative group, P = 0.0001). Uptake of genetic counseling among eligible patients was 47 % in the migrant group and 56 % in the comparative group; differences in uptake were seen among the patients diagnosed before 40 years of age (48 % in the migrant group vs 81 % in the comparative group; P = 0.021). When adjusted for age at diagnosis, ethnicity was associated with discussing referral to genetic counseling and its actual uptake. The Turkish/Moroccan ethnicity appears to be associated with a lower uptake of genetic counseling, mainly caused by the lower uptake in the young age-group. The major barrier to participation in genetic counseling seems to lie within the referral process.     

Cortical cerebral microinfarcts on 7T MRI: Risk factors,neuroimaging correlates and cognitive functioning – The Medea-7T study

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28–2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18–7.43), cortical infarcts (RR = 5.28, 95%CI 2.91–9.55), lacunes (RR = 5.66, 95%CI 2.85–11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27–5.84) and decreased cerebral blood flow (RR = 1.35 per −100 ml/min, 95%CI 1.00–1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05–0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.     

Progression risk of columnar cell lesions of the breast diagnosed in core needle biopsies

Columnar cell lesions (CCLs) of the breast are recognized as putative precursor lesions of invasive carcinoma, but their management remains controversial. We therefore conducted a retrospective study on 311 CCLs, diagnosed in 4,164 14-gauge core needle biopsies (CNB): 221 CCLs without atypia (CCL), 69 with atypia (CCL-A), and 21 atypical ductal hyperplasias originating in CCL (ADH-CCL). Two groups were identified: "immediate treatment" group undergoing excision within four months after the CNB diagnosis of CCL (N = 52) and the "wait-and-see" group followed up to 8 years (median 3.5 years, N = 259). In 7 of 31 women (22.5%, 1 CCL, 4 CCL-A, 2 ADH-CCL) who underwent immediate surgical excision and were initially biopsied for microcalcifications, ductal carcinoma in situ (DCIS) was present and in 2/31 women (6.5%, 1 CCL, 1 CCL-A) invasive carcinoma. In 2/21 excisions (9.5%, 1 CCL, 1 CCL-A) initially biopsied for a density, DCIS was present and invasive carcinoma in 5/21 excisions (23.8%, 2 CCL, 3 CCL-A). In the wait-and-see group, 9/259 women (3.5%) developed invasive carcinoma, 6 ipsi, and 3 contralaterally. Progression risks of CCL-A and ADH-CCL were 18% and 22%,versus 2% for CCL without atypia (p < 0.001). In conclusion, CCL-A or ADH-CCL in a CNB were associated with a high risk of DCIS/invasive carcinoma in immediate surgical excision biopsies. The 8-years progression risks for CCL-A and ADH-CCL were around 20%. This illustrates that an atypical CCL in a CNB may signal the presence of concurrent lesions or development of advanced lesions in future and may justify ("mini") surgical excision.     

Alterations in total and high-molecular-weight adiponectin after 3 weeks of moderate alcohol consumption in premenopausal women

Moderate alcohol consumption is associated with increased concentrations of adiponectin. Whether this is the case for both total and high-molecular-weight (HMW) adiponectin is uncertain. Furthermore, the rate at which this increase occurs is unclear. Therefore, we examined the effect of moderate alcohol consumption on total and HMW adiponectin. In a randomized, crossover trial, 24 premenopausal women who were regular alcohol consumers received beer (∼26 g alcohol) or alcohol-free beer daily for 3 weeks preceded by a 1-week washout. Blood samples were collected weekly after an overnight fast for measurement of total and HMW adiponectin and markers of glucose and lipid metabolism. There was a significant interaction (P < .05) between the 2 treatments over time for both plasma HMW and total adiponectin concentrations. Within 3 weeks, plasma total (8.2%, P = .01) and HMW (8.2%, P = .02) adiponectin levels were higher after moderate alcohol consumption compared with abstention. Changes over time in total adiponectin were positively associated with changes in HMW adiponectin during the nonalcoholic beer (r = 0.80; 95% confidence interval, 0.55-0.92) and beer (r = 0.82; 0.58-0.93) intervention. Alcohol consumption did not affect the ratio of HMW to total adiponectin or the serum glucose, insulin, hemoglobin A_1c, or triglyceride levels compared with abstention during the intervention periods. Both total and HMW adiponectin concentrations are higher after moderate alcohol consumption compared with abstention in premenopausal women. These effects were evident after at least 3 weeks of consumption and occurred concomitantly.     

Efficacy of ‘radioguided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial

For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisation. Women (>18 years.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99?m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with negative margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86?%) patients in the ROLL group versus 134/152 (88?%) patients in the WGL group (P?=?0.644). Re-excision was required in 19/162 (12?%) patients in the ROLL group versus 15/152 (10?%) (P?=?0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64?cm³, P?=?0.017). No significant differences were seen in the duration and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first multicentre randomised controlled comparison of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care.     

A pilot study on tertiary teledermatology: feasibility and acceptance of telecommunication among dermatologists

Tertiary teledermatology (TTD), where a general dermatologist consults a specialized dermatologist on difficult cases, is a relatively new telemedicine service. We evaluated TTD in a Dutch university hospital, where 13 general dermatologists used TTD to consult 11 specialized dermatologists and two residents at the university medical centre. We measured the avoided referrals to the university centre, the usability of the system and the user acceptance of it. During a three-month study, general dermatologists consulted via TTD 28 times. In 17 of the consultations (61%), the general dermatologists would have referred their patients to the university centre if teledermatology had not been available. Referral was not necessary after teledermatology for 12 of these 17 consultations (71%). The mean usability score (0-100) of all the users was 80. All dermatologists were satisfied with TTD (mean satisfaction of 7.6 on a 10-point scale) and acceptance was high. The baseline measurements showed that half of tertiary referrals were suitable for TTD. These results suggest that TTD reduces unnecessary physical referrals and that users are satisfied with it. A large-scale evaluation is now required.     

A multicentre evaluation of the guidelines for the use of cyclosporin A in severe psoriasis

Background Controversy still exists as lo whether a dosage scheme for the treatment of severe psoriasis with cyclosporin A (CsA) should start with low dosages (3 mg/kg/day) or rather with high dosages (5 mg/kg/day). Aims In this open prospective multi-centre trial guidelines for the use of CsA in psoriasis beginning with low dosages were evaluated. A secondary aim of the study was to elucidate factors predicting efficacy of CsA treatment. Methods Efficacy and tolerability of CsA were evaluated monthly during 16 weeks in 86 patients (56 males, 30 females, mean age 43,0 ± 14,9 years) suffering from chronic severe plaque-type psoriasis, not responding to topical therapy (mean PASI 18.0 ± 8.1). All patients started with 3 mg/kg/day. Patients were defined as responders with a PASI reduction > 25% at month 1, ≥ 25% at month 1, ≥ 60% at month 3 and ≥ 70% at month 4. When a patient was a failure, the dose was increased by 1 mg/kg/day lo a maximum of 5 mg/kg/day. Results A gradual mean PASI reduction of 38%. 59%, 72% to 76% was reached with a mean CsA dose of 3.0, 3.2, 3.5, and 3.6 mg/kg/day at weeks 4, 8, 12 and 16. respectively. At the end of the study period, 39 patients were still on 3, 24 patients were on 4 and 15 patients were on 5 mg/kg/day. Due to subjective side-effects 6 patients dropped out on 3 mg/kg/day and 2 on 4 mg/kg/day. Diastolic and systolic blood pressure and creatinine levels were stable. Overall, CsA was relatively well tolerated. Absence of previous therapies, low baseline PASI and failure at week 4 were predictive for higher drop-out and failure rate and lower PASI at the end of study. Conclusions This study shows that a significant proportion of severe psoriasis patients can be treated with 3 mg/kg/day CsA with good tolerability and excellent clinical results. It is concluded that a treatment scheme with an optimal risk-benefit ratio should start with low dosages of CsA (3 mg/kg/day).