Topical Non-Steroidal Anti-Inflammatory Drugs for Management of Pain after Photorefractive Keratectomy - a Systematic Review and Network Meta-Analysis.

TOPIC: Topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for Management of Pain in Patients After Photorefractive Keratectomy (PRK). CLINICAL RELEVANCE: Pain after PRK is a major concern for both patients and surgeons. While evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDS. METHODS: The study was prospectively registered with PROSPERO (ID -CRD42023417651). A systematic search of electronic databases was done, for randomized control trials (RCTs) reporting topical NSAIDs' outcomes of corneal reepithelization, rescue analgesics intake, and pain in days 0-3 after PRK (POD0-3). Studies were graded for risk of bias. Data were extracted and Standardized Mean Differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which frequentist approach model was fitted. Transitivity was assessed using the net-split method. Treatment effectiveness was ranked using forest plots based on comparison to placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons. RESULTS: Out of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0 ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95%CI [-1.86, -0.52]), POD2 (P 0.882, SMD -1.05, 95%CI [-1.82, -0.27]), and POD3 (P 0.939, SMD -1.14, 95%CI [-2.1, -0.18]). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95%CI [-1.33, -0.27]), ketorolac, and diclofenac. Compared to placebo, reepithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95%CI [-1.38, -0.03]). CONCLUSIONS: Flurbiprofen was favorable in pain scores on typically postoperative painful days and reepithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAIDs effect sizes should be taken into consideration.

Group A Streptococcus emm gene types in pharyngeal isolates, Ontario, Canada, 2002-2010.

Group A Streptococcus (GAS) is a human-adapted pathogen that causes a variety of diseases, including pharyngitis and invasive infections. GAS strains are categorized by variation in the nucleotide sequence of the gene (emm) that encodes the M protein. To identify the emm types of GAS strains causing pharyngitis in Ontario, Canada, we sequenced the hypervariable region of the emm gene in 4,635 pharyngeal GAS isolates collected during 2002-2010. The most prevalent emm types varied little from year to year. In contrast, fine-scale geographic analysis identified inter-site variability in the most common emm types. Additionally, we observed fluctuations in yearly frequency of emm3 strains from pharyngitis patients that coincided with peaks of emm3 invasive infections. We also discovered a striking increase in frequency of emm89 strains among isolates from patients with pharyngitis and invasive disease. These findings about the epidemiology of GAS are potentially useful for vaccine research.

Distinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populations.

Many pathogens colonize different anatomical sites, but the selective pressures contributing to survival in the diverse niches are poorly understood. Group A Streptococcus (GAS) is a human-adapted bacterium that causes a range of infections. Much effort has been expended to dissect the molecular basis of invasive (sterile-site) infections, but little is known about the genomes of strains causing pharyngitis (streptococcal "sore throat"). Additionally, there is essentially nothing known about the genetic relationships between populations of invasive and pharyngitis strains. In particular, it is unclear if invasive strains represent a distinct genetic subpopulation of strains that cause pharyngitis. We compared the genomes of 86 serotype M3 GAS pharyngitis strains with those of 215 invasive M3 strains from the same geographical location. The pharyngitis and invasive groups were highly related to each other and had virtually identical phylogenetic structures, indicating they belong to the same genetic pool. Despite the overall high degree of genetic similarity, we discovered that strains from different host environments (i.e., throat, normally sterile sites) have distinct patterns of diversifying selection at the nucleotide level. In particular, the pattern of polymorphisms in the hyaluronic acid capsule synthesis operon was especially different between the two strain populations. This finding was mirrored by data obtained from full-genome analysis of strains sequentially cultured from nonhuman primates. Our results answer the long-standing question of the genetic relationship between GAS pharyngitis and invasive strains. The data provide previously undescribed information about the evolutionary history of pathogenic microbes that cause disease in different anatomical sites.