METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).
RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.
CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.
METHODS: All patients diagnosed with FBPase deficiency from 2010 to 2015 were included in this study. Their clinical and laboratory data were collected retrospectively.
RESULTS: All the patients presented with recurrent episodes of hypoglycemia, metabolic acidosis, hyperlactacidemia and hepatomegaly. All of them had the first metabolic decompensation prior to 2 years old. The common triggering factors were vomiting and infection. Biallelic mutations in FBP1 gene (MIM*611570) were identified in all seven patients confirming the diagnosis of FBPase deficiency. In four patients, genetic study was prompted by detection of glycerol or glycerol-3-phosphate in urine organic acids analysis. One patient also had pseudo-hypertriglyceridemia. Seven different mutations were identified in FBP1, among them four mutations were new: three point deletions (c.392delT, c.603delG and c.704delC) and one splice site mutation (c.568-2A > C). All four new mutations were predicted to be damaging by in silico analysis. One patient presented in the neonatal period and succumbed due to sepsis and multi-organ failure. Among six survivors (current age ranged from 4 to 27 years), four have normal growth and cognitive development. One patient had short stature and another had neurological deficit following status epilepticus due to profound hypoglycemia.
CONCLUSION: FBPase deficiency needs to be considered in any children with recurrent hypoglycemia and metabolic acidosis. Our study expands the spectrum of FBP1 gene mutations.
METHODS: Review of hospital case notes on patients with juvenile GPP.
RESULTS: Twenty-seven patients with juvenile GPP were identified. Female to male ratio was 1.4:1. The median age at onset of GPP was 6.5 years. Ten patients had prior psoriasis with a median pre-pustular duration of 2.7 years. Onset of GPP was earlier in patients without prior psoriasis (5.1 years vs. 12.0 years, P = 0.002). Precipitating factors identified included stress, upper respiratory tract infection, systemic steroid use, vaccination, and pregnancy. A positive family history of psoriasis and GPP was present in six and one patient(s), respectively. Twenty-one patients had acute, five annular, and one localized variant of GPP. Arthritis was present in 22.2%. Fever, leukocytosis, and transaminitis were mainly seen in patients with acute GPP at 80.9, 72.2, and 11.1%, respectively. Among 20 patients screened, eight carry IL36RN variants and one has CARD14 mutation. IL36RN-positive patients have more severe disease characterized by early onset, low prevalence of prior plaque psoriasis, high prevalence of systemic inflammation, and need for continuous long-term systemic therapy. Acitretin and cyclosporine were effective in aborting acute GPP in 100% of 16 and 66.7% of six patients treated, respectively. However, relapses were common. Only three of the 17 patients whose initial acute GPP was controlled with systemic agents were successfully weaned off treatment.
CONCLUSIONS: Juvenile GPP is a chronic recalcitrant disease. IL36RN-positive patients have more severe disease.
METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups.
CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis.
METHOD: This is a cross-sectional study of schoolchildren aged 9-15 years based in Kuala Langat, a rural district located in the south-west of the Malaysian state of Selangor. Schoolchildren were selected randomly and given questionnaires to fill in. This was followed by interview with the children on the same day by one of the authors (CCMB) to ensure consistency of response. Recurrent abdominal pain was defined as 'at least three episodes of abdominal pain, severe enough to affect their activities over a period longer than three months' [1]. The children were also asked to answer either 'yes' or 'no' to whether they had experienced various life events in the previous year.
RESULTS: A sample of 1462 schoolchildren (722 boys and 740 girls) aged between 9 and 15 years were included in the study. There were 768 Malays, 393 Chinese and 301 Indians. Of these 1462 children, 161 (11.0%) had recurrent abdominal pain. On performing multiple logistic regression analysis, two life events were significantly associated with recurrent abdominal pain: death of a family member (P = 0.008; odds ratio 0.61, 95% CI 0.43-0.88) and a change in occupation of an immediate family member (P = 0.003; odds ratio 0.53, 95% CI 0.35-0.81).
CONCLUSION: This study suggests that recurrent abdominal pain in children is associated with recent stressful life events in the children's lives.