Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn's disease

Background Crohn’s disease (CD) is a chronic inflammatory disorder that can involve any part of the gastrointestinal tract. 5‐Aminosalicylates (5‐ASAs) are locally acting, anti‐inflammatory compounds that reduce inflammation of the colonic mucosa with release profiles that vary among various commercially available formulations. This updated Cochrane review summarizes current evidence on the use of 5‐ASA formulations for maintenance of surgically‐induced remission in CD. Objectives To assess the efficacy and safety of 5‐ASA agents for the maintenance of surgically‐induced remission in CD. Search methods We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register from inception to 16 July 2018. We also searched references, conference abstracts, and trials registers. Selection criteria Randomised controlled trials (RCTs) that included participants with CD in remission following surgery and compared 5‐ASAs to no treatment, placebo or any other active intervention with duration of at least three months were considered for inclusion. Data collection and analysis We used standard methodological procedures expected by Cochrane. The primary outcome was clinical relapse. Secondary outcomes included endoscopic recurrence, radiologic and surgical relapse, adverse events, serious adverse events and withdrawal due to adverse events. Main results Fourteen RCTs (1867 participants) were included in the review. Participants (15 to 70 years) were recruited from gastroenterology hospitals and medical clinics in Europe and North America and followed up between 3 and 72 months. The risk of bias was assessed as 'low' in one study, 'unclear' in seven and as 'high' in six. At 12 months, 36% (20/55) of participants in the 5‐ASA group experienced clinical relapse compared to 51% (28/55) in the no treatment control group (RR 0.71, 95% CI 0.46 to 1.10; low certainty evidence). Moderate certainty evidence suggests that 5‐ASAs are more effective for preventing clinical relapse than placebo. During a follow‐up period of 12 to 72 months, 36% (131/361) of 5‐ASA participants relapsed compared to 43% (160/369) of placebo participants (RR 0.83, 95% CI 0.72 to 0.96; I² = 0%; moderate certainty evidence). At 12 months, 17% (17/101) of the 4 g/day mesalamine group relapsed compared to 26% (27/105) of the 2.4 g/day group (RR 0.65, 95% CI 0.38 to 1.13; moderate certainty evidence). There was no evidence of a difference in clinical relapse rates when 5‐ASA compounds were compared to purine antimetabolites. At 24 months, 61% (103/170) of mesalamine participants relapsed compared to 67% (119/177) of azathioprine participants (RR 0.90, 95% CI 0.76 to 1.07; I² = 28%; low certainty evidence). During 24 months, 50% (9/18) of 5‐ASA participants had clinical relapse compared to 13% (2/16) of adalimumab participants (RR 4.0, 95% CI 1.01 to 15.84; low certainty evidence). The effects of sulphasalazine compared to placebo on clinical relapse rate is uncertain. After 18 to 36 months, 66% (95/143) of participants treated with sulphasalazine relapsed compared to 71% (110/155) in the placebo group (RR 0.88, 95% CI 0.56 to 1.38; I² = 38%; low certainty evidence). The effect of 5‐ASA drugs on safety was uncertain. During 24 months follow‐up, 4% (2/55) of 5‐ASA participants experienced adverse events compared to none (0/55) in the no treatment control group (RR 5.00, 95% CI 0.25 to 101.81; very low certainty evidence). An equal proportion of 5‐ASA participants (10%; 23/241) and placebo (9%; 20/225) groups experienced an adverse event during a follow‐up of 3 to 72 months (RR 1.07, 95% CI 0.60 to 1.91; I² = 0%; low certainty evidence). Adverse event rates were similar in the 5‐ASA and purine analogues groups. However, serious adverse events and withdrawals due to adverse events were more common in participants who received purine analogues than 5‐ASA. At 52 weeks to 24 months, 52% (107/207) of 5‐ASA participants had an adverse event compared to 47% (102/218) of purine analogue participants (RR 1.11, 95% CI 0.97 to 1.27, I² = 0%; low certainty evidence). Four per cent (6/152) of 5‐ASA participants had a serious adverse event compared to 17% (27/159) of purine analogue participants (RR 0.30, 95% CI 0.11 to 0.80; very low certainty evidence). Eight per cent (17/207) of 5‐ASA participants withdrew due to an adverse event compared to 19% (42/218) of purine analogue participants (RR 0.48, 95% CI 0.28 to 0.83; low certainty evidence). Adverse event rates were similar in high and low dose mesalamine participants. After 12 months, 2% (2/101) of 4 g/day mesalamine participants had an adverse event compared to 2% (2/105) of 2.4 g/day participants (RR 1.04, 95% CI 0.15 to 7.24; low certainty evidence). The proportion of participants who experienced adverse events over a 24 month follow‐up in the mesalamine group was 78% (14/18) compared to 69% (11/16) of adalimumab participants (RR 1.13, 95% CI 0.75 to 1.71; very low certainty evidence). None (0/32) of the sulphasalazine participants had an adverse event at 18 months follow‐up compared to 3% (1/34) of the placebo group (RR 0.35, 95% CI 0.01 to 8.38; very low certainty evidence). Commonly reported adverse events in the included studies were diarrhoea, nausea, increased liver function tests, pancreatitis, and abdominal pain. Authors' conclusions 5‐ASA preparations are superior to placebo for the maintenance of surgically‐induced clinical remission in patients with CD (moderate certainty). The number needed to treat to prevent one relapse was 13 patients. The evidence for endoscopic remission is uncertain. The sulphasalazine class of 5‐ASA agents failed to demonstrate superiority against placebo, 5‐ASAs failed to demonstrate superiority compared to no treatment (very low and low certainty). The efficacy of two different doses of the same 5‐ASA and the efficacy of 5‐ASA compared to purine antimetabolites (azathioprine or 6‐mercaptopurine) in maintaining surgically‐induced remission of CD remains unclear. However, purine analogues lead to more serious adverse events and discontinuation due to adverse events. There is a low certainty that 5‐ASA is inferior for maintaining surgically‐induced remission of CD compared to biologics (anti TNF‐ɑ). 5‐ASA formulations appear to be safe with no difference in the occurrence of adverse events or withdrawal when compared with placebo, no treatment or biologics

12-year survival of composite vs. amalgam restorations.

Contains fulltext : 89725.pdf (publisher's version ) (Closed access)Information about the long-term clinical survival of large amalgam and composite restorations is still lacking. This retrospective study compares the longevity of three- and four-/five-surface amalgam and composite restorations relative to patients' caries risk. Patient records from a general practice were used for data collection. We evaluated 1949 large class II restorations (1202 amalgam/747 composite). Dates of placement, replacement, and failure were recorded, and caries risk of patients was assessed. Survival was calculated from Kaplan-Meier statistics. After 12 years, 293 amalgam and 114 composite restorations had failed. Large composite restorations showed a higher survival in the combined population and in the low-risk group. For three-surface restorations in high-risk patients, amalgam showed better survival.1 oktober 201

Specialist paediatric dentistry in Sweden 2008 - a 25-year perspective

Background. Paediatric dentistry in Sweden has been surveyed four times over the past 25 years. During this period postgraduate training, dental health, and the organization of child dental care have changed considerably. Aim. To investigate services provided by specialists in paediatric dentistry in Sweden in 2008, and to compare with data from previous surveys. Design. The same questionnaire was sent to all 30 specialist paediatric dental clinics in Sweden that had been used in previous surveys. Comparisons were made with data from 1983, 1989, 1996 and 2003. Results. Despite an unchanged number of specialists (N = 81 in 2008), the number of referrals had increased by 16% since 2003 and by almost 50% since 1983. There was greater variation in reasons for referrals. The main reason was still dental anxiety/behaviour management problems in combination with dental treatment needs (27%), followed by medical conditions/disability (18%), and high caries activity (15%). The use of different techniques for conscious sedation as well as general anaesthesia had also increased. Conclusions. The referrals to paediatric dentistry continue to increase, leading to a heavy work load for the same number of specialists. Thus, the need for more paediatric dentists remains