Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

BACKGROUND: Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. CASE PRESENTATION: A 14-year-old Chinese boy suffering from β–thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. CONCLUSION: This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Long term outcome of primary non-surgical root canal treatment

published_or_final_versionEndodonticsMasterMaster of Dental Surger

PROMs Following Root Canal Treatment and Surgical Endodontic Treatment

The FDI is currently working on developing a tool to encompass patient-reported outcome measures (PROMs) within the overall assessment of outcomes of endodontic treatment. The outcome of endodontic treatment has traditionally been determined by various clinical and radiographic criteria. However, these parameters do not address the impact of treatment on a patient's oral health–related quality of life (OHRQoL). OHRQoL, a crucial PROM, can be used to understand treatment outcome from a patient-centred perspective, thus improving clinician–patient communication whilst guiding decision-making. This focussed review aims to recount the OHRQoL of patients following nonsurgical root canal treatment and surgical endodontic treatment, with a specific focus on the minimal important difference (MID; the minimum score changes of an outcome instrument for a patient to register a clinically significant change in their OHRQoL and/or oral condition) and the methods used to determine it. The current evidence indicates that the OHRQoL of patients requiring root canal treatment is poorer than those without such need. Accordingly, the literature suggests that OHRQoL improves following nonsurgical or surgical endodontic treatment. However, study methodologies vary widely, and conclusions cannot be drawn with high confidence, nor can MID recommendations be provided. Well-designed clinical studies with baseline measurements and appropriate follow-up time frames are therefore needed. Despite that the literature is rife with outcome studies, research on PROMs is an area that deserves greater attention, particularly in relation to the MID. Determining the MID will facilitate the understanding of changes in outcome scores from the patients’ perspective, thus allowing for more informed decision-making in clinical practice

Antimicrobial Effects of L-Chg10-Teixobactin against Enterococcus faecalis In Vitro

Objective: Teixobactin and its analogues are a new class of antibiotics that have no detectable bacterial resistance. This study was designed to determine the antibacterial and antibiofilm activities of a novel teixobactin analogue, L-Chg10-teixobactin, against two strains of Enterococcus faecalis (E. faecalis). Materials and Methods: The efficacy of L-Chg10-teixobactin against two strains of E. faecalis (ATCC 29212 and 47077) was determined using Clinical and Laboratory Standards Institute methods. L-Chg10-teixobactin was prepared at a stock concentration of 1 mg/mL in 5% DMSO. The minimum inhibitory concentration (MIC) was calculated using a two-fold serial broth dilution method, utilizing a 96-well plate. The minimum bactericidal concentration (MBC) was determined by plating the bacteria onto agar to define the concentration that resulted in 99.9% of bacterial death. Ampicillin was used as the control. The effect of L-Chg10-teixobactin on the inhibition of ATCC 47077 strain biofilm formation was determined by measuring the minimum biofilm inhibitory concentration (MBIC) using the safranin assay, while the eradication of the preformed biofilm was determined by measuring the minimum biofilm eradication concentration (MBEC) using the XTT assay. For nonlinear data, the log dose–response curve was plotted to calculate the optimum concentration using Excel (version 16.51, Microsoft® excel. 2021, Microsoft Corporation, Reymond, WA, USA). The data are presented as mean ± standard deviation (SD). Results: The MIC and MBC values of L-Chg10-teixobactin against both strains of E. faecalis were 0.8 μg/mL. The MIC of ampicillin was 1.25 μg/mL for ATCC 29212 and ranged from 1.25 to 5 μg/mL for ATCC 47077. The MBC of ampicillin for ATCC 29212 and ATCC 47077 was 10 and 20 μg/mL, respectively. The MIC and MBC of ampicillin were much higher compared with those of L-Chg10-teixobactin. The MBEC80 of L-Chg10-teixobactin was 4.60 μg/mL for ATCC 47077, which was much lower than that of ampicillin (20 μg/mL). Conclusions:L-Chg10-teixobactin demonstrated potent antibacterial and antibiofilm effects against E. faecalis, suggesting its potential role an effective antibacterial and antibiofilm agent in endodontic treatment

Enterococcus faecalis Shields Porphyromonas gingivalis in Dual-Species Biofilm in Oxic Condition

Aim: To develop a reproducible biofilm model consisting of Enterococcus faecalis (E. faecalis) and Porphyromonas gingivalis (P. gingivalis) and to evaluate the interaction between the two bacterial species. Methodology: E. faecalis and P. gingivalis were grown in mono-culture, sequential, and co-culture models for 96 h in a 96-well polystyrene microtiter plate under both aerobic and anaerobic conditions separately. The viability of the two bacterial species in the biofilms was quantified by polymerase chain reaction (qPCR). Biofilm thickness and protein contents were measured using confocal laser scanning microscopy (CLSM). Two-way analysis of variance (ANOVA) was performed to analyze cell viability and biofilm thickness among different culture models cultivated under either aerobic or anaerobic conditions. The level of significance was set at p < 0.05. Results: Different culture models tested did not show any significant difference between the viable cell counts of both E. faecalis and P. gingivalis cultivated under aerobic and anaerobic conditions (p > 0.05). Biofilm was significantly thicker (p < 0.05) in the co-culture models compared to the mono-culture and sequential models. Protein contents in the biofilms were more pronounced when both bacterial species were co-cultured under aerobic conditions. Conclusions: E. faecalis appeared to shield P. gingivalis and support its continued growth in oxic (aerobic) conditions. The co-culture model of E. faecalis and P. gingivalis produced a significantly thicker biofilm irrespective of the presence or absence of oxygen, while increased protein contents were only observed in the presence of oxygen

A multimodal cell census and atlas of the mammalian primary motor cortex

none258Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.openCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; McCarroll, Steven A.; McMillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; McCracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, SusanCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; Mccarroll, Steven A.; Mcmillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; Mccracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, Susa

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially