Browsing by Subject "CLINICAL-TRIAL"

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  • Uusi-Rasi, Kirsti; Patil, Radhika; Karinkanta, Saija; Kannus, Pekka; Tokola, Kari; Lamberg-Allardt, Christel; Sievanen, Harri (2017)
    Background: Both exercise and vitamin D are recommended means to prevent falls among older adults, but their combined effects on fallinduced injuries are scarcely studied. Methods: A 2-year follow-up of a previous 2-year randomized controlled trial with vitamin D and exercise (Ex) of 409 older home-dwelling women using a factorial 2 x 2 design (D(-)Ex(-), D(+)Ex(-), D(-)Ex(+), D(+)Ex(+)). Besides monthly fall diaries, femoral neck bone mineral density (fn-BMD), and physical functioning were assessed at 1 and 2 years after the intervention. Results: After the intervention, S-25OHD concentrations declined to baseline levels in both supplement groups. The groups did not differ for change in fn-BMD or physical functioning, except for leg extensor muscle strength, which remained about 10% greater in the exercise groups compared with the reference group (D(-)Ex(-)). There were no between-group differences in the rate of all falls, but medically attended injurious falls reduced in D+ Ex-and D(-)Ex(+) groups compared with D(-)Ex(-). However, all former treatment groups had less medically attended injured fallers, HRs (95% CI) being 0.62 (0.39-1.00) for D+ Ex-, 0.46 (0.28-0.76) for D(-)Ex(+), and 0.55 (0.34-0.88) for D(+)Ex(+), compared with D(-)Ex(-). Conclusions: Exercise-induced benefits in physical functioning partly remained 2 years after cessation of supervised training. Although there was no difference in the rate of all falls, former exercise groups continued to have lower rate of medically attended injured fallers compared with referents even 2 years after the intervention. Vitamin D without exercise was associated with less injurious falls with no difference in physical functioning.
  • Sippola, Suvi; Grönroos, Juha; Sallinen, Ville; Rautio, Tero; Nordström, Pia; Rantanen, Tuomo; Hurme, Saija; Leppäniemi, Ari; Meriläinen, Sanna; Laukkarinen, Johanna; Savolainen, Heini; Virtanen, Johanna; Salminen, Paulina (2018)
    Introduction Recent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In CT-confirmed uncomplicated acute diverticulitis (left-sided appendicitis), studies have shown no benefit from antibiotics compared with symptomatic treatment, but this shift from antibiotics to symptomatic treatment has not yet been widely implemented in clinical practice. Recently, symptomatic treatment of uncomplicated acute appendicitis has been demonstrated in a Korean open-label study. However, a double-blinded placebo-controlled study to illustrate the role of antibiotics and spontaneous resolution of uncomplicated acute appendicitis is still lacking. Methods and analysis The APPAC III (APPendicitis ACuta III) trial is a multicentre, double-blind, placebo-controlled, superiority randomised study comparing antibiotic therapy with placebo in the treatment CT scan-confirmed uncomplicated acute appendicitis aiming to evaluate the role of antibiotics in the resolution of uncomplicated acute appendicitis. Adult patients (18-60 years) with CT scan-confirmed uncomplicated acute appendicitis (the absence of appendicolith, abscess, perforation and tumour) will be enrolled in five Finnish university hospitals. Primary endpoint is success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without surgical intervention within 10 days after initiating randomised treatment (treatment efficacy). Secondary endpoints include postintervention complications, recurrent symptoms after treatment up to 1year, late recurrence of acute appendicitis after 1year, duration of hospital stay, sick leave, treatment costs and quality of life. A decrease of 15 percentage points in success rate is considered clinically important difference. The superiority of antibiotic treatment compared with placebo will be analysed using Fisher's one-sided test and CI will be calculated for proportion difference. Ethics and dissemination This protocol has been approved by the Ethics Committee of Turku University Hospital and the Finnish Medicines Agency (FIMEA). The findings will be disseminated in peer-reviewed academic journals. Trial registration number NCT03234296; Pre-results.
  • Bellomo, Rinaldo; Kellum, John A.; Ronco, Claudio; Wald, Ron; Martensson, Johan; Maiden, Matthew; Bagshaw, Sean M.; Glassford, Neil J.; Lankadeva, Yugeesh; Vaara, Suvi; Schneider, Antoine (2017)
    Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.
  • Zafar, Sadia; Quixabeira, Dafne Carolina Alves; Kudling, Tatiana Viktorovna; Cervera-Carrascon, Victor; Santos, Joao Manuel; Grönberg-Vähä-Koskela, Susanna; Zhao, Fang; Aronen, Pasi; Heiniö, Camilla; Havunen, Riikka; Sorsa, Suvi; Kanerva, Anna; Hemminki, Akseli (2021)
    Oncolytic adenoviruses are promising cancer therapeutic agents. Clinical data have shown adenoviruses' ability to transduce tumors after systemic delivery in human cancer patients, despite antibodies. In the present work, we have focused on the interaction of a chimeric adenovirus Ad5/3 with human lymphocytes and human erythrocytes. Ad5/3 binding with human lymphocytes and erythrocytes was observed to occur in a reversible manner, which allowed viral transduction of tumors, and oncolytic potency of Ad5/3 in vitro and in vivo,with or without neutralizing antibodies. Immunodeficient mice bearing xenograft tumors showed enhanced tumor transduction following systemic administration, when Ad5/3 virus was bound to lymphocytes or erythrocytes (P <0.05). In conclusion, our findings reveal that chimeric Ad5/3 adenovirus reaches non-injected tumors in the presence of neutralizing antibodies: it occurs through reversible binding to lymphocytes and erythrocytes.
  • Kormi, Eeva; Snall, Johanna; Koivusalo, Anna-Maria; Suominen, Anna Liisa; Thoren, Hanna; Tornwall, Jyrki (2017)
    Purpose: To clarify the effect of systemic dexamethasone (DXM) on pain and postoperative opioid (oxycodone) consumption after blowout fracture surgery. Materials and Methods: A prospective randomized observer-blinded trial of 20 patients who had a blowout fracture requiring surgical intervention was conducted. Patients were randomly assigned to receive a total dose of intravenous DXM 30 mg perioperatively or no DXM (controls). Pain was assessed postoperatively using a 10-cm visual analog scale (VAS) each time analgesics (acetaminophen every 6 hours or oxycodone upon request) were administered. The VAS area under the curve (VAS AUC) for 24 hours postoperatively represented the outcome. Data were analyzed using chi(2) test, Student t test, 2-tailed Mann-Whitney U test, and linear regression, with a P value less than .05 indicating significance. Results: Patients with blowout fracture receiving perioperative systemic DXM exhibited a significantly lower average VAS AUC (P = .04). After controlling for other confounding variables, this result remained significant (P = .03). Conclusions: DXM appears to decrease postoperative pain and thus is recommended as a pre-emptive analgesic in blowout fracture surgery. (C) 2017 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons
  • Di Saverio, Salomone; Coccolini, Federico; Galati, Marica; Smerieri, Nazareno; Biffl, Walter L.; Ansaloni, Luca; Tugnoli, Gregorio; Velmahos, George C.; Sartelli, Massimo; Bendinelli, Cino; Fraga, Gustavo Pereira; Kelly, Michael D.; Moore, Frederick A.; Mandala, Vincenzo; Mandala, Stefano; Masetti, Michele; Jovine, Elio; Pinna, Antonio D.; Peitzman, Andrew B.; Leppäniemi, Ari; Sugarbaker, Paul H.; Van Goor, Harry; Moore, Ernest E.; Jeekel, Johannes; Catena, Fausto (2013)
  • Mattila, Anne; Mrena, Johanna; Kautiainen, Hannu; Nevantaus, Juha; Kellokumpu, Ilmo (2016)
    To examine the impact of day-care laparoscopic cholecystectomy (LC) with ultrasonic scissors dissection versus diathermy hook dissection method in a randomized setting. From April 2012 to September 2014, a total of 169 elective day-care patients were randomized to undergo either laparoscopic cholecystectomy with ultrasonic scissors using fundus-first approach (n = 88) or diathermy hook dissection starting from the triangle of Calot (n = 79). Main measures of outcome were operative time, same-day discharge and intraoperative complications. Secondary outcome measures were postoperative pain (numeric rating scale), postoperative nausea and vomiting (PONV), readmissions and 30-day morbidity. Median operative time was similar in the ultrasonic dissection and diathermy hook dissection groups (45 vs 45 min, p = 0.95). Same-day discharge was possible in 77 patients (87 %) in the ultrasonic dissection group and in 69 patients (87 %) in the diathermy group, p = 0.98. Intraoperative gallbladder perforations, mean intraoperative bleeding, postoperative pain and PONV at 1, 2 and 4 h (p = 0.78) did not differ significantly between the study groups. Day-care LC using either diathermy hook or ultrasonic dissection resulted in excellent same-day discharge in both groups (87 %). LC with ultrasonic dissection does not offer any clinical advantages compared to diathermy dissection.
  • Matikainen, M.; Aro, E.; Vironen, J.; Kössi, J.; Hulmi, T.; Silvasti, S.; Ilves, I.; Hertsi, M.; Mustonen, K.; Paajanen, H. (2018)
    Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10-30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs. Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n = 216), non-absorbable sutures with partially absorbable mesh (n = 207) or self-gripping polyesther mesh (n = 202). Factors related to chronic pain (visual analogue scores; VAS ae 30, range 0-100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery. At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years' follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p = 0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain. Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.
  • Huttunen, Henri J.; Palva, J. Matias; Lindberg, Laura; Palva, Satu; Saarela, Ville; Karvonen, Elina; Latvala, Marja-Leena; Liinamaa, Johanna; Booms, Sigrid; Castren, Eero; Uusitalo, Hannu (2018)
    Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p <0.001) and placebo (-0.194 logMAR; 95% CI: -0.254 to -0.133; p <0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.
  • Wang, Haining; Liu, Ye; Tian, Qing; Yang, Jin; Lu, Ran; Zhan, Siyan; Haukka, Jari; Hong, Tianpei (2018)
    Aims: To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM). Materials and Methods: For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of >= 52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate. Results: A total of 33 studies (n = 79971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for >= 104 weeks, 84 pancreatic cancer events were identified in 59919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95). Conclusions: Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for 104 weeks.
  • Gregson, Barbara A.; Broderick, Joseph P.; Auer, Ludwig M.; Batjer, Hunt; Chen, Xian-Cheng; Juvela, Seppo; Morgenstern, Lewis B.; Pantazis, George C.; Teernstra, Onno P. M.; Wang, Wen-Zhi; Zuccarello, Mario; Mendelow, A. David (2012)
  • Lyra, Anna; Hillilä, Markku; Huttunen, Teppo; Mannikko, Sofia; Taalikka, Mikko; Tennila, Julia; Tarpila, Anneli; Lahtinen, Sampo; Ouwehand, Arthur C.; Veijola, Lea (2016)
    AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS In this randomized triple-blind trial, adult IBS volunteers who were recruited according to Rome. criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score (IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk runin period, after 4 and 12 wk of intervention, and after a 4-wk washout. RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean +/- SD of 44.0 +/- 80.2, 50.8 +/- 82.4, and 48.3 +/- 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline (VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 +/- 22.8, 29.4 +/- 17.9, and 31.2 +/- 21.9 in the placebo, active low-dose, and active high-dose groups, respectively (P value for placebo vs combined active doses = 0.0460). CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.
  • Hulkko, A. P.; Murray, G. K.; Moilanen, J.; Haapea, M.; Rannikko, I.; Jones, P. B.; Barnett, J. H.; Huhtaniska, S.; Isohanni, M. K.; Koponen, H.; Jaaskelainen, E.; Miettunen, J. (2017)
    Background: Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia. Methods: Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression. Results: Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition. Conclusions: Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia. (C) 2017 Elsevier Masson SAS. All rights reserved.
  • Sakalis, Vasileios I.; Karavitakis, Markos; Bedretdinova, Dina; Bach, Thorsten; Bosh, J. L. H. Ruud; Gacci, Mauro; Gratzke, Christian; Herrmann, Thomas R.; Madersbacher, Stephan; Mamoulakis, Charalampos; Tikkinen, Kari A. O.; Gravas, Stavros; Drake, Marcus J. (2017)
    Context: The treatment of nocturia is a key challenge due to the multi-factorial pathophysiology of the symptom and the disparate outcome measures used in research. Objective: To assess and compare available therapy options for nocturia, in terms of symptom severity and quality of life. Evidence acquisition: Medical databases (Embase, Medline, Cochrane Systematic Reviews, Cochrane Central) were searched with no date restriction. Comparative studies were included which studied adult men with nocturia as the primary presentation and lower urinary tract symptoms including nocturia or nocturnal polyuria. Outcomes were symptom severity, quality of life, and harms. Evidence synthesis: We identified 44 articles. Antidiuretic therapy using dose titration was more effective than placebo in relation to nocturnal voiding frequency and duration of undisturbed sleep; baseline serum sodium is a key selection criterion. Screening for hyponatremia (<130 mmol/l) must be undertaken at baseline, after initiation or dose titration, and during treatment. Medications to treat lower urinary tract dysfunction (alpha-1 adrenergic antagonists, 5-alpha reductase inhibitors, phosphodiesterase type 5inhibitor, antimuscarinics, beta-3 agonist, and phytotherapy) were generally not significantly better than placebo in short-term use. Benefits with combination therapies were not consistently observed. Other medications (diuretics, agents to promote sleep, nonsteroidal anti-inflammatories) were sometimes associated with response or quality of life improvement. The recommendations of the Guideline Panel are presented. Conclusions: Issues of trial designmake therapy of nocturia a challenging topic. The range of contributory factors relevant in nocturia makes it desirable to identify predictors of response to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For other therapies, responses were less certain, and potentially of limited clinical benefit. Patient summary: This review provides an overview of the current drug treatments of nocturia, which is the need to wake at night to pass urine. The symptom can be caused by several different medical conditions, and measuring its severity and impact varies in separate research studies. No single treatment deals with the symptom in all contexts, and careful assessment is essential to make suitable treatment selection. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Sallinen, V.; Akl, E. A.; You, J. J.; Agarwal, A.; Shoucair, S.; Vandvik, P. O.; Agoritsas, T.; Heels-Ansdell, D.; Guyatt, G. H.; Tikkinen, K. A. O. (2016)
    Background: For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. Methods: A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Five studies including 1116 patients reported major complications in 25 (4.9 per cent) of 510 patients in the antibiotic and 41 (8.4 per cent) of 489 in the appendicectomy group: risk difference -2.6 (95 per cent c.i. -6.3 to 1.1) per cent (low-quality evidence). Minor complications occurred in 11 (2.2 per cent) of 510 and 61 (12.5 per cent) of 489 patients respectively: risk difference -7.2 (-18.1 to 3.8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8.2 (95 per cent c.i. 5.2 to 11.8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22.6 (15.6 to 30.4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. Conclusion: The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value-and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.
  • European Consortium Minimally Inva; van Hilst, Jony; Korrel, Maarten; Kokkola, Arto; Dijkgraaf, Marcel G. (2021)
    Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.
  • Knip, Mikael; Honkanen, Jarno (2017)
    Purpose of Review The purpose of this review is to summarize potential modulations of the intestinal microbiome aimed at preventing or delaying progression to overt type 1 diabetes in the light of recently identified perturbations of the gut microbiota associated with the development of type 1 diabetes. Recent Findings Accumulated data suggest that the gut microbiota is involved at two different steps in the evolution of type 1 diabetes. At the first step, the intestinal tract is colonized by a microbial community unable to provide an adequate education of the immune system. As a consequence, the infant acquires susceptibility to immune-mediated diseases, type 1 diabetes included. At the other step, the young child seroconverts to positivity for diabetes-associated autoantibodies. This is preceded or accompanied by a decrease in the diversity of the intestinal microbiota and an increased abundance of Bacteroides species. These changes will affect the disease process promoting progression toward overt type 1 diabetes. Summary By providing specific probiotics, one can affect the colonization of the intestinal tract in the newborn infant or strengthen the immune education in early life. Human milk oligosaccharides function as nutrients for "healthy" bacteria. Dietary interventions applying modified starches can influence the numbers and activities of both autoreactive and regulatory T cells and provide protection against autoimmune diabetes in non-obese diabetic mice. Modulation of the intestinal microbiome holds the promise of effective protection against human type 1 diabetes.
  • Karppinen, Toni; Ala-Houhala, Meri; Ylianttila, Lasse; Kautiainen, Hannu; Viljakainen, Heli; Reunala, Timo; Snellman, Erna (2016)
    Exposure to solar ultraviolet B radiation during the summer months is the main source of vitamin D (VD) for people living in northern latitudes. The aim of this study was to determine whether artificial narrowband ultraviolet B (NB-UVB) whole-body exposures could maintain VD levels in winter. The intervention group received 2 standard erythema doses (SEDs) of NB-UVB exposures every second week from October 2013 to April 2014. In October 2013 serum 25-hydroxyvitamin D concentrations were 78.3 nmol/l in the intervention group (n=16) and 76.8 nmol/l in the control group (n=18). By April 2014 the concentrations had increased by 11.7 nmol/l (p=0.029) in the intervention group and decreased by 11.1 nmol/l (p=0.022) in the control group. The baseline VD concentration showed a negative correlation (p=0.012) with body mass index (BMI). In conclusion, a suberythemal NB-UVB dose of 2 SED every second week maintains and even increases serum VD concentrations during the winter. A high BMI seems to predispose subjects to low levels of VD.
  • Turner, Dan; Yerushalmi, Baruch; Kori, Michal; Broide, Efrat; Mozer-Glassberg, Yael; Shaoul, Ron; Kolho, Kaija-Leena; Shteyer, Eyal; Shamaly, Hussein; Ledder, Oren; Cohen, Shlomi; Peleg, Sarit; On, Avi; Levine, Arie (2017)
    Background: Trials in adults suggested that, in ulcerative colitis [UC], once-daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective than twice-daily [BD] dosing. In this induction of remission, investigator-blinded, randomised controlled-trial, we aimed to compare effectiveness and safety of once-versus twice-daily mesalazine in paediatric UC. Methods: Children, aged 4-18 years with a PUCAI [Paediatric Ulcerative Colitis Activity Index] of 10-55 points at inclusion, were randomised in blocks of six with blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The primary outcome was mean PUCAI score at Week 6. Results: A total of 83/86 randomised children were eligible and analysed: 43 in the OD group and 40 in the BD group (mean age 14 +/- 2.7 years, 43 [52%] males, 51 [62%] extensive colitis). The groups did not differ with regard to disease activity or any other parameter at baseline. There was no difference in median PUCAI score between the OD group and BD group at Week 6: 15 (interquartile range [IQR] 5-40) versus 10 [0-40]; p = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78]. Proportion of children in remission [PUCAI <10] at Week 6 was 13 [30%] OD versus 16 [40%] BD; p = 0.35]. Most adverse events were related to disease aggravation; the rates of serious adverse events were similar [p > 0.2]. Conclusions: In this first randomised controlled trial in children, no differences were found between OD and BD dosing for any clinical outcome. Remission was achieved in 35% of children treated with mesalazine for active UC.