Criteria to assess potential reverse innovations: opportunities for shared learning between high- and low-income countries.

BACKGROUND: Low- and middle-income countries (LMICs) are developing novel approaches to healthcare that may be relevant to high-income countries (HICs). These include products, services, organizational processes, or policies that improve access, cost, or efficiency of healthcare. However, given the challenge of replication, it is difficult to identify innovations that could be successfully adapted to high-income settings. We present a set of criteria for evaluating the potential impact of LMIC innovations in HIC settings. METHODS: An initial framework was drafted based on a literature review, and revised iteratively by applying it to LMIC examples from the Center for Health Market Innovations (CHMI) program database. The resulting criteria were then reviewed using a modified Delphi process by the Reverse Innovation Working Group, consisting of 31 experts in medicine, engineering, management and political science, as well as representatives from industry and government, all with an expressed interest in reverse innovation. RESULTS: The resulting 8 criteria are divided into two steps with a simple scoring system. First, innovations are assessed according to their success within the LMIC context according to metrics of improving accessibility, cost-effectiveness, scalability, and overall effectiveness. Next, they are scored for their potential for spread to HICs, according to their ability to address an HIC healthcare challenge, compatibility with infrastructure and regulatory requirements, degree of novelty, and degree of current collaboration with HICs. We use examples to illustrate where programs which appear initially promising may be unlikely to succeed in a HIC setting due to feasibility concerns. CONCLUSIONS: This study presents a framework for identifying reverse innovations that may be useful to policymakers and funding agencies interested in identifying novel approaches to addressing cost and access to care in HICs. We solicited expert feedback and consensus on an empirically-derived set of criteria to create a practical tool for funders that can be used directly and tested prospectively using current databases of LMIC programs.

Pediatric Postoperative Pulse Oximetry Monitoring During Transport to the Postanesthesia Care Unit Reduces Frequency of Hypoxemia.

BACKGROUND: The standard use of pulse oximetry during the transport of postoperative patients from the operating room (OR) to the postanesthesia care unit (PACU) is not routinely practiced. A study was conducted to determine if the frequency of hypoxemia on admission to the PACU decreased after implementation of routine use of transport pulse oximeters for postoperative patients being transferred to the PACU. METHODS: In this prospective cohort study, which was conducted at an academic pediatric hospital, the primary outcome measure was the frequency of hypoxemic events on arrival to the PACU. RESULTS: A total of 506 patients in the preintervention phase and 597 in the postintervention phase met the inclusion criteria. Six hypoxemic events on arrival to the PACU were identified in preintervention phase versus zero in the postintervention period, p = 0.009. Use of oxygen monitors during transport from the OR to the PACU increased from 0% to 100%, p < 0.0001, in the postintervention phase. The median duration of unmonitored time during transport decreased from 272 seconds to 13 seconds, p < 0.0001. Of the 605 patients who met the inclusion criteria for sustainment audits-conducted 18 months after the postimplementation evaluation-99.8% were transported to the PACU with a pulse oximeter, and there were zero reported hypoxemic patients on PACU admission. CONCLUSION: The routine use of portable oxygen monitoring when transferring patients from the OR to the PACU is a low-cost, noninvasive safety measure that should be considered at any institution performing pediatric general anesthesia.

Implementation of a standardized postanesthesia care handoff increases information transfer without increasing handoff duration.

BACKGROUND: In the transition of a patient from the operating room (OR) to the postanesthesia care unit (PACU), it was hypothesized that (1) standardizing the members of sending and receiving teams and (2) requiring a structured handoff process would increase the overall amount of patient information transferred in the OR-to-PACU handoff process. METHODS: A prospective cohort study was conducted at a 311-bed freestanding academic pediatric hospital in Northern California. The intervention, which was conducted in February-March 2013, consisted of (1) requiring the sending team to include a surgeon, an anesthesiologist, and a circulating nurse, and the receiving team to include the PACU nurse; (2) standardizing the content of the handoff on the basis of literature-guided recommendations; and (3) presenting the handoff verbally in the I-PASS format. Data included amount of patient information transferred, duration of handoff, provider presence, and nurse satisfaction. RESULTS: Forty-one audits during the preimplementation phase and 45 audits during the postimplementation phase were analyzed. Overall information transfer scores increased significantly from a mean score of 49% to 83% (p < .0001). Twenty-two PACU nurse satisfaction surveys were completed after the preimplementation phase and 14 surveys were completed in the postimplementation phase. Paired mean total satisfaction scores increased from 36 to 44 (p =. 004). The duration of the handoffs trended downward from 4.1 min to 3.5 min (p = 0.10). CONCLUSION: A standardized, team-based approach to OR-to-PACU handoffs increased the quantity of patient information transferred, increased PACU nurse satisfaction, and did not increase the handoff duration.

Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome.

CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup [p.Arg367SerfsX33]) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development.

Micronanostructures of the scales on a mosquito's legs and their role in weight support.

We show here that the mosquito cannot only give rise to a higher water-supporting force than the water strider if the ratio of the water-supporting force to the body weight of the insect itself is compared, but also can safely take off or land on the water surface, and also can attach on any solid surface like the fly. We found that the mosquito's legs are covered by numerous scales consisting of the uniform microscale longitudinal ridges (nanoscale thickness and microscale spacing between) and nanoscale cross ribs (nanoscale thickness and spacing between). Such special delicate microstructure and/or nanostructure on the leg surface give a water contact angle of approximately 153 degrees and give a surprising high water-supporting ability. It was found that the water-supporting force of a single leg of the mosquito is about 23 times the body weight of the mosquito, compared with a water strider's leg giving a water-supporting force of about 15 times the body weight of the insect.

Chikungunya Virus Sequences Across the First Epidemic in Nicaragua, 2014-2015.

Chikungunya is caused by the mosquito-borne arthrogenic alphavirus, chikungunya virus (CHIKV). Chikungunya was introduced into the Americas in late 2013 and Nicaragua in mid-2014. Here, we sequenced five imported and 30 autochthonous Nicaraguan CHIKV from cases identified in the first epidemic in the country between August 2014 and April 2015. One full-length and two partial genomic sequences were obtained by deep sequencing; Sanger methodology yielded 33 E1 sequences from five imported and 28 autochthonous cases. Phylogenetic analysis indicates that Nicaraguan CHIKV all belonged to the Asian genotype, Caribbean clade. Moreover, E1 gene sequences revealed accumulation of mutations in later months of the epidemic, including four silent mutations in 11 autochthonous cases and three non-synonymous mutations in three autochthonous cases. No mutations contributing to increased transmissibility by Aedes albopictus were identified in the E1 gene. This represents the most comprehensive set of CHIKV sequences available from the Americas to date.

RAC1 activation drives pathologic interactions between the epidermis and immune cells.

Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions.

Second Global Symposium on Health Systems Research: a conference impact evaluation.

Evaluation researchers have confirmed the importance of conference evaluation, but there remains little research on the topic, perhaps in part because evaluation methodology related to conference impact is underdeveloped. We conducted a study evaluating a 4-day long health conference, the Second Global Symposium on Health Systems Research (HSR), which took place in Beijing in November 2012. Using a conference evaluation framework and a mixed-methods approach that involved in-conference surveys, in-conference interviews and 7-month post-conference interviews, we evaluated the impact of the Symposium on attendees' work and the field of health systems research. The three major impacts on participants' work were new knowledge, new skills and new networks, and many participants were able to provide examples of how obtaining new knowledge, skills or collaborations had changed the way they conduct their work. Participants noted that the Symposium influenced the field of HSR only in so far as it influenced the capacity of stakeholders, but did not lead to any high level agenda or policy changes, perhaps due to the insufficient length of time (7 months) between the Symposium and post-conference follow-up. This study provides an illustration of a framework useful for conference organizers in the evaluation of future conferences, and of a unique methodology for evaluation researchers.

Competition between ADAR and RNAi pathways for an extensive class of RNA targets.

Adenosine deaminases that act on RNAs (ADARs) interact with double-stranded RNAs, deaminating adenosines to inosines. Previous studies of Caenorhabditis elegans indicated an antagonistic interaction between ADAR and RNAi machineries, with ADAR defects suppressed upon additional knockout of RNAi. This suggests a pool of common RNA substrates capable of engaging both pathways. To define and characterize such substrates, we examined small RNA and mRNA populations of ADAR mutants and identified a distinct set of loci from which RNAi-dependent short RNAs are markedly upregulated. At these same loci, we observed populations of multiply edited transcripts, supporting a specific role for ADARs in preventing access to the RNAi pathway for an extensive population of dsRNAs. Characterization of these loci revealed a substantial overlap with noncoding and intergenic regions, suggesting that the landscape of ADAR targets may extend beyond previously annotated classes of transcripts.