The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.Methods: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.
Forty-three patients averaging 28.2 (range 16-74) years with open fractures of the lower limbs were studied prospectively for 40 weeks using anthropometrical, biochemical and haematological parameters to ascertain their relationship to wound healing following injury. Nearly half (21/43) of the patients were malnourished at admission and the number increased to 22 a week after injury. Dietary advice and better food intake improved nutritional status with only 13 patients remaining malnourished at the 40th week. Wound healing was earlier when creatinine-height index was normal throughout the course of treatment and was delayed when serum albumin level was low.Résumé Nous avons suivi prospectivement, pendant quarante semaines, 43 malades avec des fractures combinées du membre inférieur en utilisant des paramètres anthropométrique, biochimique et hématologique pour étudier leur relation avec la cicatrisation des parties molles après l'accident. Prés de la moitié des patients (21/43) étaient considérés comme malnutris à leur admission. Les conseils diététiques et une meilleure prise de la nourriture ont amélioré le statut nutritionnel avec seulement treize malades dans le groupe malnutris à la quarantième semaine. La guérison des blessures était plus précoce quand l'index de créatinine était normal durant le cours du traitement et a été retardée quand le niveau de sérum albumine était bas.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus. The exon1 variants at codon 52, 54, and 57 have been reported to augment the risk of SLE in different ethnic populations. Three hundred South Indian Tamil patients with SLE and 460 age-, sex-, and ethnicity-matched controls were genotyped for three polymorphisms at codon 52, 54, and 57 in exon1 of MBL gene by Taqman real-time PCR. The three polymorphisms in exon1 of MBL were observed not to confer risk of developing SLE. However, MBL codon 54 rs1800450 polymorphism was associated with the development of medium vessel vasculitis and gangrene (OR-2.29, CI 95% 1.08-4.83, p = 0.02), whereas, the ancestral allele G conferred protection (OR-0.44, CI 95% 0.21-0.93, p = 0.02). Genetic variants in the exon1 of MBL gene per se are not risk factors for SLE in South Indian Tamils. However, the association of codon 54 (rs1800450) with medium vessel vasculitis suggests that it may be a genetic modifier of clinical phenotype in SLE.
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