Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.

PURPOSE: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room. METHODS: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail. These constructs are intended to allow decisions about protocol deviations, such as changes to design or model specification, to be made without knowledge of how they might affect subsequent analyses. We describe an example for implementing staging with a clean room. RESULTS: Stage 1 may involve selecting a data source, developing and registering a protocol, establishing a clean room, and applying inclusion/exclusion criteria. Stage 2 may involve attempting to achieve covariate balance, often through propensity score models. Stage 3 may involve evaluating the presence of residual confounding using negative control outcomes. After each stage, check points may be implemented when a team of statisticians, epidemiologists and clinicians masked to how their decisions may affect study outcomes, reviews the results. This review team may be tasked with making recommendations for protocol deviations to address study precision or bias. They may recommend proceeding to the next stage, conducting additional analyses to address bias, or terminating the study. Stage 4 may involve conducting the comparative analyses. CONCLUSIONS: The staging and clean room constructs are intended to protect the integrity and enhance confidence in the results of analyses of RWD.

Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study.

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.

Revisiting monovision for presbyopia.

PURPOSE OF REVIEW: Presbyopia is an inevitable age-related loss of accommodation that results in spectacle dependence with common everyday near-vision tasks. Many surgical approaches to presbyopic correction have been investigated, with monovision correction being amongst the most common and attractive options. In this article, we will review the advantages and disadvantages of the new modalities of presbyopic monovision correction. RECENT FINDINGS: New methods such as mini-monovision, corneal inlays, and multifocal corneal ablation aim to maximize stereopsis and decrease the anisometropic side effects of conventional monovision. These include inlays such as the KAMRA and Raindrop, and phakic intraocular lenses such as the hole ICL. Newer corneal laser refractive procedures such as small incision lenticule extraction have also shown good outcomes with monovision. Pseudophakic monovision using standard monofocal lenses still provides good results. SUMMARY: Monovision for presbyopic correction continues to provide promising results. There are a number of new devices and techniques that have shown good visual acuity outcomes, patient satisfaction and spectacle independence.

Tear film assessments for the diagnosis of dry eye.

PURPOSE OF REVIEW: Dry eye disease (DED) is a complex, multifactorial condition that is challenging to diagnose and monitor clinically. To date, diagnosis has consisted largely of self-reported symptom questionnaires and a collection of clinical tests including vital dye staining, estimation of tear breakup time and Schirmer's testing, as no gold standard exists. As the dry eye field has made progress in understanding disease pathogenesis, new methods for assessment of this condition have been developed. RECENT FINDINGS: DED is now known to be characterized by tear hyperosmolarity and ocular surface inflammation, and there are now commercially available devices that accurately and reliably measure tear osmolarity and matrix metalloproteinase 9, a marker of inflammation and tissue breakdown. In addition, there are a variety of imaging modalities that have shown promise in their ability to identify patients with DED by assessing tear film dimensions and tear film instability. SUMMARY: There is a significant need for the development of tear film assessments for accurate diagnosis and monitoring of dry eye. There are a number of new devices and techniques that have shown promise in their ability help clinicians manage patients with DED.

Vascular resection and reconstruction at pancreatico-duodenectomy: technical issues.

BACKGROUND: With the improvement of perioperative management over the years, pancreatico-duodenectomy has become a safe operation despite its technical complexity. The presence of concomitant visceral artery occlusion unrelated to the underlying malignancy and concomitant major venous infiltration by tumor poses additional hazards to resection which could compromise the postoperative outcome. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the key words "median arcuate ligament syndrome", "superior mesenteric artery", "replaced right hepatic artery", and "portal vein resection". Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Computed tomography with 3-dimensional reconstruction of the vascular anatomy provides most key information on the potential vascular problems encountered during surgery. A trial clamping of the gastroduodenal artery provides a simple intraoperative assessment for the presence of any significant visceral arterial occlusion. Depending on the timing of diagnosis, division of the median arcuate ligament, bypass or endovascular stenting should be considered. Portal and superior mesenteric vein resection had been used with increasing frequency and safety. The steps and methods taken to reconstruct the venous continuity vary with individual surgeons, and the anatomical variations encountered. With segmental loss of the portal vein, opinions differs with regard to the preservation of the splenic vein, and when divided, the necessity of restoring its continuity; source of the autologous vein graft when needed and whether the use of synthetic graft is a safe alternative. CONCLUSIONS: During a pancreatico-duodenectomy, images of computed tomography must be carefully studied to appreciate the changes and variation of vascular anatomy. Adequate preoperative preparation, acute awareness of the probable arterial and venous anatomical variation and the availability of expertise, especially micro-vascular surgery, for vascular reconstruction would help to make the complex pancreatic resection a safer procedure.

Management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis utilizing amniotic membrane and topical corticosteroids.

PURPOSE: To describe the results of a novel treatment approach to the acute ophthalmic management of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Retrospective interventional case series. METHODS: setting: Institutional. study population: Sixteen eyes of 8 patients with acute, biopsy-proven SJS or TEN and significant ophthalmic involvement. interventional procedure(s): Application of amniotic membrane to the ocular surface, either in the operating room or at the bedside, and short-term use of intensive topical corticosteroid medication. main outcome measures: Visual acuity, slit-lamp appearance of the ocular surface, and patients' subjective impression of ocular comfort. RESULTS: Two patients expired during the hospitalization. Mean follow-up time for the surviving patients was 7.7 months. Four surviving patients in whom the entire ocular surface (ie, the cornea, bulbar and palpebral conjunctiva, and eyelid margins) was treated with amniotic membrane retained visual acuities of 20/40 or better and an intact ocular surface. In contrast, the initial 2 patients in the study who were treated with only a Prokera device or unsutured amniotic membrane sheets, leaving the palpebral conjunctiva and eyelid margins uncovered, developed more significant ocular surface abnormalities, and 1 developed a corneal perforation. CONCLUSIONS: Amniotic membrane coverage of the ocular surface in its entirety coupled with the use of intensive short-term topical corticosteroids during the acute phase of SJS and TEN is associated with the preservation of good visual acuity and an intact ocular surface. Partial amniotic membrane coverage of the ocular surface may not serve to minimize the cicatrizing ocular sequelae of SJS and TEN as effectively as complete coverage.