Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji

Introduction: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries. Methods and analysis: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being. Ethics: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University. Trial registration number: ACTRN12618000633280; Pre-results

Bioequivalence assessment: a pharmaceutical industry perspective.

Various aspects of bioequivalence are investigated in this paper. Some aspects dealing with bioequivalence studies conducted either during the development of the drug or after its marketing will be presented and discussed: Bioequivalence of highly variable drugs with the associated problem of widening the acceptance range or alternative solutions. Bioequivalence for the final market image. Bioequivalence for investigating the food effect. Bioequivalence in special population such as children, non Caucasian population. Bioequivalence based on in vitro data or literature. New approaches in bioequivalence interpretation. Bioequivalence and analytical methods which are not sensitive or specific enough

Influence of exercise on nitroglycerin plasma concentrations after transdermal application.

Nitroglycerin plasma concentrations following transdermal application were measured in nine healthy subjects during supine rest position or during supine rest interrupted by sitting or exercising for 20 min. Sitting led to almost doubling of the average plasma concentrations (0.31 ng ml-1 before sitting, 0.55 ng ml-1 at the end of the sitting period), but exercise was accompanied by a much more marked increase in average plasma concentrations, which reached its maximum 5 min after ending exercise (0.22 ng ml-1 before exercise, 1.26 ng ml-1 5 min after the exercise period). Changes of bioavailability as well as of systemic clearance might be involved in the exercise-induced increase in plasma nitroglycerin concentrations

Clinical evaluation of different alveolar ridge preservation techniques after tooth extraction: a randomized clinical trial

OBJECTIVE The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional alterations after tooth extraction, based on clinical measurements. BACKGROUND Alveolar ridge preservation (ARP) is a common procedure in every day clinical practice, when dental implants are involved in treatment planning. In ARP procedures, a bone grafting material is combined with a socket sealing (SS) material in order to compensate the alveolar ridge dimensional alterations after tooth extraction. Xenograft and allograft are the most frequently used bone grafts in ARP, while free gingival graft (FGG), collagen membrane, and collagen sponge (CS) usually applied as SS materials. The evidence comparing xenograft and allograft directly in ARP procedure is scarce. In addition, FGG is usually combined with xenograft as SS material, while the evidence combing allograft with FGG is absent. Moreover, CS could probably be an alternative choice in ARP as SS material, since it has been used in previous studies but more clinical trials are required to evaluate its effectiveness. MATERIALS AND METHODS Forty-one patients were randomly assigned in four treatment groups: (A) freeze-dried bone allograft (FDBA) covered with collagen sponge (CS), (B) FDBA covered with free gingival graft (FGG), (C) demineralized bovine bone mineral xenograft (DBBM) covered with FGG, and (D) FGG alone. Clinical measurements were performed immediately after tooth extraction and 4 months later. The related outcomes pertained to both vertical and horizontal assessment of bone loss. RESULTS Overall, groups A, B, and C presented significantly less vertical and horizontal bone resorption compared to group D. No statistically significant difference was observed between allograft and xenograft, except for the vertical bone resorption at the buccal central site, where xenograft showed marginally statistically significantly reduced bone loss compared to allograft (group C vs group B: adjusted β coef: 1.07 mm; 95%CI: 0.01, 2.10; p = 0.05). No significant differences were observed in hard tissue dimensions when CS and FGG were applied over FDBA. CONCLUSIONS No differences between FDBA and DBBM could practically be confirmed. In addition, CS and FGG were equally effective socket sealing materials when combined with FDBA, regarding bone resorption. More RCTs are needed to compare the histological differences between FDBA and DBBM and the effect of CS and FGG on soft tissue dimensional changes. CLINICAL RELEVANCE Xenograft and allograft were equally efficient in ARP 4 months after tooth extraction in horizontal level. Xenograft maintained the mid-buccal site of the socket marginally better than the allograft, in vertical level. FGG and CS were equally efficient as SS materials regarding the hard tissue dimensional alterations. TRIAL REGISTRATION Clinical trial registration Number: NCT04934813 (clinicaltrials.gov)

Uveal effusion syndrome in 104 eyes: Response to corticosteroids – The 2017 Axel C. Hansen lecture

Purpose: The purpose of the study was to investigate the corticosteroids for uveal effusion syndrome (UES). Methods: Retrospective series of 104 eyes with UES treated with oral corticosteroids (OCS), periocular corticosteroids (PCS), topical corticosteroids (TCS), or observation (OBS). Main outcome measure was UES resolution. Results: Of 104 eyes, treatment included OCS (n = 27), PCS (n = 12), TCS (n = 11), and OBS (n = 54). A comparison of the four groups (OCS vs. PCS vs. TCS vs. OBS) revealed differences in those managed with OCS versus OBS as younger (66 vs. 72 years, P = 0.049), PCS versus OBS as male (100% vs. 54%, P = 0.002), PCS versus OBS with decreased visual acuity (VA)/visual field (91% vs. 51%, P = 0.018), and OBS versus OCS as asymptomatic (28% vs. 0%, P = 0.001). Of the 59 with follow-up information, management included OCS (n = 21), PCS (n = 12), TCS (n = 6), and OBS (n = 20). There were differences in initial VA <20/400 in PCS versus OBS (42% vs. 5%, P = 0.018), effusion thickness in TCS versus OCS (7 vs. 3 mm, P = 0.004), and serous retinal detachment in PCS versus OBS (100% vs. 30%, P < 0.001) and PCS versus OCS (100% vs. 57%, P = 0.012). Regarding outcomes, VA showed less worsening in OCS versus OBS (0% vs. 30%, P = 0.008) and OCS versus PCS (0% vs. 33%, P = 0.012). There was no difference in rate of effusion resolution or effusion recurrence. Overall, using combination of corticosteroid therapies, effusion resolution was achieved in 56/59 (95%) cases and the need for surgical management with scleral windows was necessary in only 3/59 (5%) cases. Complications included cataract (n = 9) and no instance of steroid-induced glaucoma. Conclusion: Management of UES is complex and depends on disease severity. Using various corticosteroid delivery routes, UES control was achieved in 95%, and scleral window surgery was required in only 5%. A trial of corticosteroids can benefit patients with UES

Type 2M von Willebrand disease - more often misidentified than correctly identified

Introduction: Appropriate diagnosis of von Willebrand disease (VWD), including differential identification of qualitative vs. quantitative von Willebrand factor (VWF) defects has important management implications, but remains problematic. Aim: The aim of the study was to assess whether 2M VWD, defining qualitative defects not associated with loss of high molecular weight (HMW) VWF, is often misidentified, given highly variable reported frequency ranging from 0 to similar to 60% of all type 2 VWD. Methods: A comparative evaluation of laboratory ability to appropriately identify 2M VWD (n = 4) vs. HMW VWF reduction (n = 4), as sent to participants of an international external quality assessment programme. Results: Laboratories had considerably greater difficulty identifying type 2M VWD, correctly identifying these on average only 29.4% of occasions, with the 70.6% error rate representing use of insufficient test panels (41.7%), misinterpretation of test results (10.0%) and analytical errors (13.3%). One type 2M case, giving a median of 49 U dL(-1) VWF:Ag, was more often misidentified as type 2A/2B VWD (46.7%) than 2M (34.8%). Another 2M case, giving a median of 189 U dL(-1) VWF:Ag, was instead often misidentified as being normal (non-VWD) (36.4%), with identifications of type 2A/2B VWD (13.6%) also represented. In comparison, errors in identification of HMW VWF reduced samples only averaged 11.5%, primarily driven by use of insufficient test panels (6.3%) or misinterpretation of results (4.2%) and infrequently analytical errors (1.0%). Conclusion: Type 2M VWD is more often misidentified (70.6%) than correctly identified as 2M VWD (29.4%), and potentially explaining the relative under-reported incidence of 2M VWD in the literature