Recent Stanford Publications in PubMed
- Expansion of laparoscopic cholecystectomy in a resource limited setting, Mongolia: a 9-year cross-sectional retrospective review.Wells KM, Lee YJ, Erdene S, Erdene S, Sanchin U, Sergelen O, Presson A, Zhang C, Rodriguez B, deVries C, Price RLancet
- Variability in mortality after caesarean delivery, appendectomy, and groin hernia repair in low-income and middle-income countries: implications for expanding surgical services.Weiser TG, Uribe-Leitz T, Fu R, Jaramillo J, Maurer L, Esquivel MM, Gawande AA, Haynes ABLancet
- Avoidable maternal and neonatal deaths associated with improving access to caesarean delivery in countries with low caesarean delivery rates: an ecological modelling analysis.Molina G, Esquivel MM, Uribe-Leitz T, Lipsitz SR, Azad T, Shah N, Semrau K, Berry WR, Gwande AA, Weiser TG, Haynes ABLancet
- The role of facility-based surgical services in addressing the national burden of disease in New Zealand: an index of surgical incidence based on country-specific disease prevalence.Hider P, Wilson L, Rose J, Weiser TG, Gruen R, Bickler SWLancet
- Injury assessment in three low-resource settings: a reference for worldwide estimates.Gupta S, Wren SM, Kamara TB, Shrestha S, Kyamanywa P, Wong EG, Groen RS, Nwomeh BC, Kushner AL, Price RRLancet
- Projections to achieve minimum surgical rate threshold: an observational study.Uribe-Leitz T, Esquivel MM, Molina G, Lipsitz SR, Verguet S, Rose J, Bickler SW, Gawande AA, Haynes AB, Weiser TGLancet
- Proposed minimum rates of surgery to support desirable health outcomes: an observational study based on four strategies.Esquivel MM, Molina G, Uribe-Leitz T, Lipsitz SR, Rose J, Bickler SW, Gawande AA, Haynes AB, Weiser TGLancet
- Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes.Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AALancet
- Surgical care needs of low-resource populations: an estimate of the prevalence of surgically treatable conditions and avoidable deaths in 48 countries.Gupta S, Groen RS, Kyamanywa P, Ameh EA, Labib M, Clarke DL, Donkor P, Derbew M, Sani R, Kamara TB, Shrestha S, Nwomeh BC, Wren SM, Price RR, Kushner ALLancet
- Precision Medicine in Breast Cancer Care: An Early Glimpse of Impact.Kurian AW, Friese CRJAMA Oncol
- Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants.Jones SA, Valayannopoulos V, Schneider E, Eckert S, Banikazemi M, Bialer M, Cederbaum S, Chan A, Dhawan A, Di Rocco M, Domm J, Enns GM, Finegold D, Gargus JJ, Guardamagna O, Hendriksz C, Mahmoud IG, Raiman J, Selim LA, Whitley CB, Zaki O, Quinn AGGenet Med
- Converting Skin Fibroblasts Into Hepatic-Like Cells by Transient Programming.Zhu X, Pan X, Yao L, Li W, Cui J, Wang G, Mrsny RJ, Hoffman AR, Hu JFJ Cell Biochem
- Pediatric disaster preparedness and response and the nation's children's hospitals.Lyle KC, Milton J, Fagbuyi D, LeFort R, Sirbaugh P, Gonzalez J, Upperman JS, Carmack T, Anderson MAm J Disaster Med
- Enzyme-Free Detection of Mutations in Cancer DNA Using Synthetic Oligonucleotide Probes and Fluorescence Microscopy.Miotke L, Maity A, Ji H, Brewer J, Astakhova KPLoS One
- Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes.Hilton HG, Guethlein LA, Goyos A, Nemat-Gorgani N, Bushnell DA, Norman PJ, Parham PJ Immunol
- IgH sequences in common variable immune deficiency reveal altered B cell development and selection.Roskin KM, Simchoni N, Liu Y, Lee JY, Seo K, Hoh RA, Pham T, Park JH, Furman D, Dekker CL, Davis MM, James JA, Nadeau KC, Cunningham-Rundles C, Boyd SDSci Transl Med
- Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design.Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Held P, Jonasson J, Minematsu K, Molina CA, Wong LKInt J Stroke
- State of the art systematic review of bone disease in anorexia nervosa.Misra M, Golden NH, Katzman DKInt J Eat Disord
- MLL leukemia induction by genome editing of human CD34+ hematopoietic cells.Buechele C, Breese EH, Schneidawind D, Lin CH, Jeong J, Duque-Afonso J, Wong SH, Smith KS, Negrin RS, Porteus M, Cleary MLBlood
- The role of passive avian head stabilization in flapping flight.Pete AE, Kress D, Dimitrov MA, Lentink DJ R Soc Interface
- Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients.Airy M, Mandayam S, Mitani AA, Chang TI, Ding VY, Brookhart MA, Goldstein BA, Winkelmayer WCNephrol Dial Transplant
- Parsing Physiological Functions of Erythropoietin One Domain at a Time.Steinman LNeurotherapeutics
- Twist-drill craniotomy for the treatment of chronic subdural hematomas and the use of the pre-coronal suture entry point.Jung H, Shah AClin Neurol Neurosurg
- Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.Zilbermintz L, Leonardi W, Jeong SY, Sjodt M, McComb R, Ho CC, Retterer C, Gharaibeh D, Zamani R, Soloveva V, Bavari S, Levitin A, West J, Bradley KA, Clubb RT, Cohen SN, Gupta V, Martchenko MSci Rep
- Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or Both.Chalhoub D, Cawthon PM, Ensrud KE, Stefanick ML, Kado DM, Boudreau R, Greenspan S, Newman AB, Zmuda J, Orwoll ES, Cauley JA, Osteoporotic Fractures in Men Study Research GroupJ Am Geriatr Soc
- An immunological view of chemotherapy.Tsung K, Norton JAImmunotherapy
- Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME, Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC)Brain
- Association of worker characteristics and early reimbursement for physical therapy, chiropractic and opioid prescriptions with workers' compensation claim duration, for cases of acute low back pain: an observational cohort study.Busse JW, Ebrahim S, Heels-Ansdell D, Wang L, Couban R, Walter SDBMJ Open
- Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KYTransl Oncol
- CMV after transplant: T-cell repertoire crooks.Meyer EBlood
- Exosomes as potential alternatives to stem cell therapy in mediating cardiac regeneration.Ong SG, Wu JCCirc Res
- Risk of Next Melanoma in Patients With Familial and Sporadic Melanoma by Number of Previous Melanomas.Chen T, Fallah M, Försti A, Kharazmi E, Sundquist K, Hemminki KJAMA Dermatol
- Multilocus adaptation associated with heat resistance in reef-building corals.Bay RA, Palumbi SRCurr Biol
- Urine drug screening: opioid risks preclude complete patient autonomy.Darnall BD, Schatman MEPain Med
- Urine drug screening: necessary or alienating?Darnall BD, Schatman MEPain Med
- Intraoperative neuromonitoring for superior semicircular canal dehiscence and hearing outcomes.Wenzel A, Ward BK, Ritzl EK, Gutierrez-Hernandez S, Della Santina CC, Minor LB, Carey JPOtol Neurotol
- Illuminating circuitry relevant to psychiatric disorders with optogenetics.Steinberg EE, Christoffel DJ, Deisseroth K, Malenka RCCurr Opin Neurobiol
- The combined subtemporal-transfacial approach for the resection of juvenile nasopharyngeal angiofibromas with intracranial extension.Kumar AR, Nayak JV, Janisiewicz AM, Li G, Oghalai JSOtol Neurotol
- Reasoning based quality assurance of medical ontologies: a case study.Horridge M, Parsia B, Noy NF, Musenm MAAMIA Annu Symp Proc
Expansion of laparoscopic cholecystectomy in a resource limited setting, Mongolia: a 9-year cross-sectional retrospective review.
Lancet. 2015 Apr 27;385 Suppl 2:S38
Authors: Wells KM, Lee YJ, Erdene S, Erdene S, Sanchin U, Sergelen O, Presson A, Zhang C, Rodriguez B, deVries C, Price R
BACKGROUND: The benefits of laparoscopic cholecystectomy have been largely unavailable to most people in developing countries. Mongolia has an extremely high incidence of gallbladder disease. In 2005, only 2% of cholecystectomies were being done laparoscopically. Open cholecystectomies were associated with high rates of wound infections, complications, and increased recovery time. Because of the unacceptable complications associated with open cholecystectomies, and nearly 50% of the nomadic population needing faster post-operative recovery times, a national project for the development of laparoscopic surgery was organised. Multi-institutional collaboration between the Mongolia Health Sciences University, the Dr W C Swanson Family Foundation (SFF), the University of Utah, Intermountain Healthcare, and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) led to the promulgation of a formalised countrywide laparoscopic training programme during the past 9 years. This is a retrospective review of the transition from open to laparoscopic cholecystectomy throughout Mongolia.
METHODS: Demographic patient data, diagnosis, and operation preformed-laparoscopic versus open cholecystectomy, between January, 2005, and September, 2013, were collected and trends were analysed from seven regional diagnostic referral and treatment centres, and two tertiary academic medical centres from six of the 21 provinces (Aimags) throughout Mongolia. Data were analysed by individual training centre, by year, and then compared between rural and urban centres.
FINDINGS: Nearly 16 000 cholecystectomies were analysed and compared (4417 [28·2%] men; 11 244 [71·8%] women). Men and women underwent laparoscopic cholecystectomy with the same frequency (41·2% men, 43·2% women) and had similar age (men, mean 52·2 years [SD 14·8]; women, mean 49·4 years [SD 15·7]). By 2013, 62% of gallbladders were removed laparoscopically countrywide as opposed to only 2% in 2005. More than 315 Mongolian practitioners have received laparoscopic training in 19 of 21 Aimags. On average 60% of cholecystectomies are done laparoscopically in urban surgical centres, up from 2%, versus 55% in rural surgical centres, up from 0%, in 2005. Laparoscopic cholecystectomy surpassed open cholecystectomy as the primary method for gallbladder removal countrywide in 2011.
INTERPRETATION: By 2013, 62% of cholecystectomies countrywide were done laparoscopically, a great increase from 9 years ago. Despite being a resource limited country, the expansion of laparoscopic cholecystectomy has transformed the care of biliary tract disease in Mongolia.
FUNDING: The University of Utah Center for Global Surgery.
PMID: 26313086 [PubMed - as supplied by publisher]
Variability in mortality after caesarean delivery, appendectomy, and groin hernia repair in low-income and middle-income countries: implications for expanding surgical services.
Lancet. 2015 Apr 27;385 Suppl 2:S34
Authors: Weiser TG, Uribe-Leitz T, Fu R, Jaramillo J, Maurer L, Esquivel MM, Gawande AA, Haynes AB
BACKGROUND: While surgical interventions occur at lower rates in resource-poor settings, rates of complication and death after surgery are substantial but have not been well quantified. A deeper understanding of outcomes is a crucial step to ensure that quality accompanies increased global access to surgical care. We aimed to assess mortality following surgery to assess the risks of such interventions in these environments.
METHODS: We collected the most recent demographic, health, and economic data from WHO for 114 countries classified as low-income or lower-middle-income according to the World Bank in 2005. We searched OVID, MedLine, PubMed, and SCOPUS to identify studies in these countries reporting all-cause mortality after three commonly performed operations: caesarean delivery, appendectomy, and groin hernia repair. Reports from governmental and other agencies were also identified. We modelled surgical mortality rates for countries without reported data with the lasso technique that performs continuous variable subset selection to avoid model overfitting. We validated our model against known case fatality rates for caesarean delivery. We aggregated mortality results by subregion to account for variability in data availability. We then created collective surgical case fatality rates by WHO region.
FINDINGS: We identified 42 countries with mortality data for at least one of the three procedures. Median reported mortality rates were 7·7 per 1000 operations for caesarean delivery (IQR 3-14), 4·0 per 1000 operations for appendectomy (IQR 0-17), and 4·7 per 1000 operations for hernia groin (IQR 0-13); all recorded deaths occurred during the same admission to hospital as the operation. Based on our model, case fatality rate estimates by subregion ranged from 0·7 (central Europe) to 13·9 (central sub-Saharan Africa) per 1000 caesarean deliveries, 5·6 (central Asia) to 6·4 (central sub-Saharan Africa) per 1000 appendectomies, and 3·5 (tropical Latin America) to 33·9 (central sub-Saharan Africa) per 1000 hernia repairs.
INTERPRETATION: All-cause postoperative mortality rates are exceedingly variable within resource-constrained environments, and substantially higher than those in middle-income and high-income settings. Efforts to expand surgical access and provision of services must include a strong commitment to improve the safety and quality of care.
PMID: 26313082 [PubMed - as supplied by publisher]
Avoidable maternal and neonatal deaths associated with improving access to caesarean delivery in countries with low caesarean delivery rates: an ecological modelling analysis.
Lancet. 2015 Apr 27;385 Suppl 2:S33
Authors: Molina G, Esquivel MM, Uribe-Leitz T, Lipsitz SR, Azad T, Shah N, Semrau K, Berry WR, Gwande AA, Weiser TG, Haynes AB
BACKGROUND: Reducing maternal and neonatal deaths are important global health priorities. We have previously shown that up to a country-level caesarean delivery rate (CDRs) of roughly 19·0%, cesarean delivery rates and maternal mortality ratio (MMR) and neonatal mortality rate (NMR) were inversely correlated. We investigated the absolute reductions in maternal and neonatal deaths if countries with low CDR increased their rates to a range of greater than 7·2% but less than or equal to 19·1%.
METHODS: We calculated maternal and neonatal deaths in 2013 and 2012, respectively, for countries with CDR 7·2% or less (N=45) with available data from the World Bank Development Indicators. We modelled the expected reduction in deaths in these countries if they had the 25th and 75th MMR and NMR percentiles observed for countries (N=48) with CDRs ranging from greater than 7·2% but less than or equal to 19·1%. This model assumes that if countries with low CDRs increased their rates of caesarean delivery to greater than 7·2% but less than or equal to 19·1%, they would achieve levels of MMR and NMR observed in countries with those CDRs.
FINDINGS: We estimate 176 078 (95% CI 163 258-188 898) maternal and 1 117 257 (95% CI 1 033 611-1 200 902) neonatal deaths occurred in 45 countries with low CDRs in 2013 and 2012, respectively. If these countries had the 25th and 75th MMR and NMR percentiles (MMR, IQR 36-190; NMR, 9-24) observed in countries (N=48) with a CDR ranging from greater than 7·2% but less than or equal to 19·1%, there would be a potential reduction of 109 762-163 513 and 279 584-803 129 maternal and neonatal deaths, respectively.
INTERPRETATION: Increasing caesarean delivery in countries with low CDRs could avert as many as 163 513 maternal deaths and 803 129 neonatal deaths annually. These findings assume that as health systems develop the capacity to deliver surgical care, there is a concurrent improvement in the quality of care and in the ability to rescue women and neonates who would otherwise die. Improving access to safe caesarean delivery should be a central focus in surgical care globally.
PMID: 26313081 [PubMed - as supplied by publisher]
The role of facility-based surgical services in addressing the national burden of disease in New Zealand: an index of surgical incidence based on country-specific disease prevalence.
Lancet. 2015 Apr 27;385 Suppl 2:S25
Authors: Hider P, Wilson L, Rose J, Weiser TG, Gruen R, Bickler SW
BACKGROUND: Surgery is a crucial component of health systems, yet its actual contribution has been difficult to define. We aimed to link use of national hospital service with national epidemiological surveillance data to describe the use of surgical procedures in the management of a broad spectrum of conditions.
METHODS: We compiled Australian Modification-International Classification of Diseases-10 codes from the New Zealand National Minimum Dataset, 2008-11. Using primary cause of admission, we aggregated admissions to 91 hospitals into 119 disease states and 22 disease subcategories of the WHO Global Health Estimate (GHE). We queried each admission for any surgical procedure in a binary manner to determine the frequency of admitted patients whose care required surgery. Surgical procedures were defined as requiring general or neuroaxial anaesthesia. We then divided the volume of surgical cases by counts of disease prevalence from the GBD 2010 to determine surgical incidence. This study was approved by the University of Otago Human Ethics Committee (Health; Reference Number HD14/42). Raw data was only handled by coauthors with direct affiliation with the New Zealand Ministry of Health.
FINDINGS: Between 2008 and 2011, there were 1 108 653 hospital admissions with 275 570 associated surgical procedures per year. Surgical procedures were associated with admissions for all 22 GHE disease subcategories and 116 of 119 GHE disease states (excluding intestinal nematode infections, iodine deficiency, and vitamin A deficiency). The subcategories with the largest surgical case volumes were unintentional injuries (48 073), musculoskeletal diseases (38 030), and digestive diseases (27 640), and the subcategories with the smallest surgical case volumes were nutritional deficiencies (13), neonatal conditions (204), and infectious and parasitic diseases (982). Surgical incidence ranged widely by individual disease states with the highest in other neurological conditions, abortion, appendicitis, obstructed labour, and maternal sepsis.
INTERPRETATION: This study confirms previous research that surgical care is required across the entire spectrum of GHE disease subcategories, showing the crucial role of operative intervention in health systems. Surgical incidence might be useful as an index to estimate the need for surgical procedures in other populations.
PMID: 26313072 [PubMed - as supplied by publisher]
Injury assessment in three low-resource settings: a reference for worldwide estimates.
Lancet. 2015 Apr 27;385 Suppl 2:S2
Authors: Gupta S, Wren SM, Kamara TB, Shrestha S, Kyamanywa P, Wong EG, Groen RS, Nwomeh BC, Kushner AL, Price RR
BACKGROUND: Trauma has become a worldwide pandemic. Without dedicated public health interventions, fatal injuries will rise 40% and become the 4th leading cause of death by 2030, with the burden highest in low-income and middle-income countries (LMICs). The aim of this study was to estimate the prevalence of traumatic injuries and injury-related deaths in low-resource countries worldwide, using population-based data from the Surgeons OverSeas Assessment of Surgical Need (SOSAS), a validated survey tool.
METHODS: Using data from three resource-poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of injury prevalence and deaths due to injury was calculated and extrapolated to low-resource countries worldwide. Injuries were defined as wounds from road traffic injuries (bus, car, truck, pedestrian, and bicycle), gunshot or stab or slash wounds, falls, work or home incidents, and burns. The Nepal study included a visual physical examination that confirmed the validity of the self-reported data. Population and annual health expenditure per capita data were obtained from the World Bank. Low-resource countries were defined as those with an annual per capita health expenditure of US$100 or less.
FINDINGS: The overall prevalence of lifetime injury for these three countries was 18·03% (95% CI 18·02-18·04); 11·64% (95% CI 11·53-11·75) of deaths annually were due to injury. An estimated prevalence of lifetime injuries for the total population in 48 low-resource countries is 465·7 million people; about 2·6 million fatal injuries occur in these countries annually.
INTERPRETATION: The limitations of this observational study with self-reported data include possible recall and desirability bias. About 466 million people at a community level (18%) sustain at least one injury during their lifetime and 2·6 million people die annually from trauma in the world's poorest countries. Trauma care capacity should be considered a global health priority; the importance of integrating a coordinated trauma system into any health system should not be underestimated.
PMID: 26313066 [PubMed - as supplied by publisher]
Projections to achieve minimum surgical rate threshold: an observational study.
Lancet. 2015 Apr 27;385 Suppl 2:S14
Authors: Uribe-Leitz T, Esquivel MM, Molina G, Lipsitz SR, Verguet S, Rose J, Bickler SW, Gawande AA, Haynes AB, Weiser TG
BACKGROUND: Recent work has indicated an increase in surgical services, especially in resource poor settings. However, the rate of growth is poorly understood and likely insufficient to meet public health needs. We previously identified a range of 4344 to 5028 operations per 100 000 population annually to be related to desirable health outcomes. From this and other evidence, the Lancet Commission on Global Surgery recommends a minimum rate of 5000 operations per 100 000 population. We evaluate rates of growth in surgery and estimate the time it will take to reach this minimum surgical rate threshold.
METHODS: We aggregated 2004 and 2012 country-level surgical rate estimates into the 21 Global Burden of Disease (GBD) regions. We calculated mean rates of surgery proportional to population size and estimate rate of growth between these years. We then extrapolated the time it will take to reach a surgical rate of 5000 operations per 100 000 population based on linear rates of change.
FINDINGS: All but two regions (central Europe and southern Latin America) experienced growth in their surgical rates during the past 8 years; the fastest growth occurred in regions with the lowest surgical rates. 14 regions representing 79% of the world's population (5·5 billion people) did not meet the recommended surgical rate threshold in 2012. If surgical capacity grows at current rates, seven regions (central sub-Saharan Africa, east Asia, eastern sub-Saharan Africa, north Africa and middle east, south Asia, southeast Asia, and western sub-Saharan Africa) will not meet the recommended surgical rate threshold by 2035; Eastern Sub-Saharan Africa will not reach this level until 2124.
INTERPRETATION: The rates of growth in surgical service delivery are exceedingly variable, but the largest growth rates were noted in the poorest regions. Although this study does not address the quality of care, and rates of surgery are unlikely to change linearly, this exercise is useful to project how many years it could take regions to reach specific surgical rates. At current rates of growth, 4·9 billion people (70% of the world's population) will still be living in countries below the minimum recommended rate of surgery in 2035. A strategy for strengthening surgical capacity is essential if these targets are to be met as part of integrated health system development.
PMID: 26313060 [PubMed - as supplied by publisher]
Proposed minimum rates of surgery to support desirable health outcomes: an observational study based on four strategies.
Lancet. 2015 Apr 27;385 Suppl 2:S12
Authors: Esquivel MM, Molina G, Uribe-Leitz T, Lipsitz SR, Rose J, Bickler SW, Gawande AA, Haynes AB, Weiser TG
BACKGROUND: The global volume of surgery in 2012 is estimated at 312·9 million operations per year, but rates of surgery vary substantially. Maternal health advocates proposed minimum caesarean delivery rates for benchmarking and to improve perinatal outcomes; however, this has not been done for surgery because the association between rates of surgical care provision as a whole and population health outcomes have not been well described. We use available data to estimate minimum rates of surgery that are associated with important health indicators.
METHODS: We defined surgical operations as procedures done in operating theatres that need general or regional anaesthesia or profound sedation to control pain. We used four strategies to identify rates of surgery based on estimated rates of surgery per country for 2012 associated with life expectancy of 74-75 years; estimated rates of surgery associated with a maternal mortality ratio of less than or equal to 100 per 100 000 live births; estimated minimum need for surgery in the 21 Global Burden of Disease (GBD) regions based on the prevalence of disorders; and surgical rates from the so-called 4C countries (Chile, China, Costa Rica, and Cuba) identified in The Lancet Commission on Global Surgery as exemplary for their achievement of high health status, despite resource limitations.
FINDINGS: Based on 2012 national surgical rates, countries with reported life expectancy of 74-75 years (n=17) had a median surgical rate of 4392 (IQR 2897-4873) operations per 100 000 population annually. The median surgical rate associated with maternal mortality ratio lower than 100 (n=109) is 5028 (IQR 4139-6778) operations per 100 000 population annually. The median surgical rate estimated for all 21 GBD regions was 4669 (IQR 4339-5291) operations per 100 000 population annually. The 4C countries had a mean surgical rate of 4344 (95% CI 2620-6068) operations per 100 000 population annually. 13 of the 21 GBD regions, accounting for 78% of the world's population, do not achieve the lowest end of the surgical rate range.
INTERPRETATION: We identified a surprisingly narrow range of surgical rates associated with important health indicators. This target range can be used for benchmarking of surgical services, and as part of a policy aimed at strengthening health-care systems and surgical capacity.
PMID: 26313058 [PubMed - as supplied by publisher]
Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes.
Lancet. 2015 Apr 27;385 Suppl 2:S11
Authors: Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AA
BACKGROUND: It was previously estimated that 234·2 million operations were performed worldwide in 2004. The association between surgical rates and population health outcomes is not clear. We re-estimated global surgical volume to track changes over time and assess rates associated with healthy populations.
METHODS: We gathered demographic, health, and economic data for 194 WHO member states. Surgical volumes were obtained from published studies and other reports from 2005 onwards. We estimated rates of surgery for all countries without available data based on health expenditure in 2012 and assessed the proportion of surgery comprised by caesarean delivery. The rate of surgery was plotted against life expectancy to describe the association between surgical care and this health indicator.
FINDINGS: We identified 66 countries reporting surgical data between 2005 and 2013. We estimate that 312·9 million operations (95% CI 266·2-359·5) took place in 2012-a 33·6% increase over 8 years; the largest proportional increase occurred in countries spending US$400 or less per capita on health care. Caesarean delivery comprised 29·8% (5·8 million operations) of the total surgical volume in poor health expenditure countries compared with 10·8% (7·8 million operations) in low health expenditure countries and 2·7% (5·1 million operations) in high health expenditure countries. We noted a correlation between increased life expectancy and increased surgical rates up to 1533 operations per 100 000 people, with significant but less dramatic improvement above this rate.
INTERPRETATION: Surgical volume is large and continues to grow in all economic environments. A single procedure-caesarean delivery-comprised almost a third of surgical volume in the most resource-limited settings. Surgical care is an essential part of health care and is associated with increased life expectancy, yet many low-income countries fail to achieve basic levels of service. Improvements in capacity and delivery of surgical services must be a major component of health system strengthening.
PMID: 26313057 [PubMed - as supplied by publisher]
Surgical care needs of low-resource populations: an estimate of the prevalence of surgically treatable conditions and avoidable deaths in 48 countries.
Lancet. 2015 Apr 27;385 Suppl 2:S1
Authors: Gupta S, Groen RS, Kyamanywa P, Ameh EA, Labib M, Clarke DL, Donkor P, Derbew M, Sani R, Kamara TB, Shrestha S, Nwomeh BC, Wren SM, Price RR, Kushner AL
BACKGROUND: Surgical care needs in low-resource countries are increasingly recognised as an important aspect of global health, yet data for the size of the problem are insufficient. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) is a population-based cluster survey previously used in Nepal, Rwanda, and Sierra Leone.
METHODS: Using previously published SOSAS data from three resource-poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of overall prevalence of surgically treatable conditions was estimated and the number of deaths that could have been avoided by providing access to surgical care was calculated for the broader community of low-resource countries. Such conditions included, but were not limited to, injuries (road traffic incidents, falls, burns, and gunshot or stab wounds), masses (solid or soft, reducible), deformities (congenital or acquired), abdominal distention, and obstructed delivery. Population and health expenditure per capita data were obtained from the World Bank. Low-resource countries were defined as those with a per capita health expenditure of US$100 or less annually. The overall prevalence estimate from the previously published SOSAS data was extrapolated to each low-resource country. Using crude death rates for each country and the calculated proportion of avoidable deaths, a total number of deaths possibly averted in the previous year with access to appropriate surgical care was calculated.
FINDINGS: The overall prevalence of surgically treatable conditions was 11·16% (95% CI 11·15-11·17) and 25·6% (95% CI 25·4-25·7) of deaths were potentially avoidable by providing access to surgical care. Using these percentages for the 48 low-resource countries, an estimated 288·2 million people are living with a surgically treatable condition and 5·6 million deaths could be averted annually by the provision of surgical care. In the Nepal SOSAS study, the observed agreement between self-reported verbal responses and visual physical examination findings was 94·6%. Such high correlation helps to validate the SOSAS tool.
INTERPRETATION: Hundreds of millions of people with surgically treatable conditions live in low-resource countries, and about 25% of the mortality annually could be avoided with better access to surgical care. Strengthening surgical care must be considered when strengthening health systems and in setting future sustainable development goals.
PMID: 26313055 [PubMed - as supplied by publisher]
Precision Medicine in Breast Cancer Care: An Early Glimpse of Impact.
JAMA Oncol. 2015 Aug 27;
Authors: Kurian AW, Friese CR
PMID: 26313021 [PubMed - as supplied by publisher]
Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants.
Genet Med. 2015 Aug 27;
Authors: Jones SA, Valayannopoulos V, Schneider E, Eckert S, Banikazemi M, Bialer M, Cederbaum S, Chan A, Dhawan A, Di Rocco M, Domm J, Enns GM, Finegold D, Gargus JJ, Guardamagna O, Hendriksz C, Mahmoud IG, Raiman J, Selim LA, Whitley CB, Zaki O, Quinn AG
PURPOSE: The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.
METHODS: Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients.
RESULTS: Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).
CONCLUSIONS: These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med advance online publication 27 August 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.108.
PMID: 26312827 [PubMed - as supplied by publisher]
Converting Skin Fibroblasts Into Hepatic-Like Cells by Transient Programming.
J Cell Biochem. 2015 Aug 27;
Authors: Zhu X, Pan X, Yao L, Li W, Cui J, Wang G, Mrsny RJ, Hoffman AR, Hu JF
Transplantation of hepatocytes is a promising therapy for end-stage liver disease, but the availability of functional cells currently precludes its clinical application. We now report a simple transient reprogramming approach to convert fibroblasts into hepatic-like cells. Human skin fibroblasts were treated with fish egg extracts to become the transiently-remodeled cells (TRCs). After infected with retroviral EGFP, they were directly injected into the fetal monkey liver, where they underwent in situ differentiation in the hepatic niche. The hepatic-like cells were functional as shown by the synthesis of hepatic markers in vivo, including albumin, cytokeratin-18, and hepatic serum antigen. Similarly, when implanted in the mouse liver, the TRCs were differentiated into hepatic-like cells that synthesize albumin and CK18 and became completely integrated into the liver parenchyma. The potency of TRCs was mechanistically related to the activation of several signal pathways, which reactivate endogenous genes related to cell potency. This study demonstrates the feasibility of a simple and inexpensive epigenetic remodeling approach to convert human fibroblasts into therapeutic hepatic-like cells for the treatment of end-stage liver disease. This article is protected by copyright. All rights reserved.
PMID: 26312781 [PubMed - as supplied by publisher]
Pediatric disaster preparedness and response and the nation's children's hospitals.
Am J Disaster Med. 2015 Spring;10(2):83-91
Authors: Lyle KC, Milton J, Fagbuyi D, LeFort R, Sirbaugh P, Gonzalez J, Upperman JS, Carmack T, Anderson M
OBJECTIVE: Children account for 30 percent of the US population; as a result, many victims of disaster events are children. The most critically injured pediatric victims would be best cared for in a tertiary care pediatric hospital. The Children's Hospital Association (CHA) undertook a survey of its members to determine their level of readiness to respond to a mass casualty disaster.
DESIGN: The Disaster Response Task Force constructed survey questions in October 2011.
SETTING AND PARTICIPANTS: The survey was distributed via e-mail to the person listed as an "emergency manager/disaster contact" at each association member hospital and was designed to take less than 15 minutes to complete.
MAIN OUTCOME MEASURES: The survey sought to determine how children's hospitals address disaster preparedness, how prepared they feel for disaster events, and how CHA could support their efforts in preparedness.
RESULTS: One hundred seventy-nine surveys were distributed with a 36 percent return rate. Seventy percent of respondent hospitals have a structure in place to plan for disaster response. There was a stronger level of confidence for hospitals in responding to local casualty events than for those responding to large-scale regional, national, and international events. Few hospitals appear to interact with nonmedical facilities with a high concentration of children such as schools or daycares.
CONCLUSIONS: Little commonality exists among children's hospitals in approaches to disaster preparedness and response. Universally, respondents can identify a disaster response plan and routinely participate in drills, but the scale and scope of these plans and drills vary substantially.
PMID: 26312491 [PubMed - as supplied by publisher]
Enzyme-Free Detection of Mutations in Cancer DNA Using Synthetic Oligonucleotide Probes and Fluorescence Microscopy.
PLoS One. 2015;10(8):e0136720
Authors: Miotke L, Maity A, Ji H, Brewer J, Astakhova K
BACKGROUND: Rapid reliable diagnostics of DNA mutations are highly desirable in research and clinical assays. Current development in this field goes simultaneously in two directions: 1) high-throughput methods, and 2) portable assays. Non-enzymatic approaches are attractive for both types of methods since they would allow rapid and relatively inexpensive detection of nucleic acids. Modern fluorescence microscopy is having a huge impact on detection of biomolecules at previously unachievable resolution. However, no straightforward methods to detect DNA in a non-enzymatic way using fluorescence microscopy and nucleic acid analogues have been proposed so far.
METHODS AND RESULTS: Here we report a novel enzyme-free approach to efficiently detect cancer mutations. This assay includes gene-specific target enrichment followed by annealing to oligonucleotides containing locked nucleic acids (LNAs) and finally, detection by fluorescence microscopy. The LNA containing probes display high binding affinity and specificity to DNA containing mutations, which allows for the detection of mutation abundance with an intercalating EvaGreen dye. We used a second probe, which increases the overall number of base pairs in order to produce a higher fluorescence signal by incorporating more dye molecules. Indeed we show here that using EvaGreen dye and LNA probes, genomic DNA containing BRAF V600E mutation could be detected by fluorescence microscopy at low femtomolar concentrations. Notably, this was at least 1000-fold above the potential detection limit.
CONCLUSION: Overall, the novel assay we describe could become a new approach to rapid, reliable and enzyme-free diagnostics of cancer or other associated DNA targets. Importantly, stoichiometry of wild type and mutant targets is conserved in our assay, which allows for an accurate estimation of mutant abundance when the detection limit requirement is met. Using fluorescence microscopy, this approach presents the opportunity to detect DNA at single-molecule resolution and directly in the biological sample of choice.
PMID: 26312489 [PubMed - as supplied by publisher]
Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes.
J Immunol. 2015 Aug 26;
Authors: Hilton HG, Guethlein LA, Goyos A, Nemat-Gorgani N, Bushnell DA, Norman PJ, Parham P
The human killer cell Ig-like receptor (KIR) locus comprises two groups of KIR haplotypes, termed A and B. These are present in all human populations but with different relative frequencies, suggesting they have different functional properties that underlie their balancing selection. We studied the genomic organization and functional properties of the alleles of the inhibitory and activating HLA-C receptors encoded by KIR haplotypes. Because every HLA-C allotype functions as a ligand for KIR, the interactions between KIR and HLA-C dominate the HLA class I-mediated regulation of human NK cells. The C2 epitope is recognized by inhibitory KIR2DL1 and activating KIR2DS1, whereas the C1 epitope is recognized by inhibitory KIR2DL2 and KIR2DL3. This study shows that the KIR2DL1, KIR2DS1, and KIR2DL2/3 alleles form distinctive phylogenetic clades that associate with specific KIR haplotypes. KIR A haplotypes are characterized by KIR2DL1 alleles that encode strong inhibitory C2 receptors and KIR2DL3 alleles encoding weak inhibitory C1 receptors. In striking contrast, KIR B haplotypes are characterized by KIR2DL1 alleles that encode weak inhibitory C2 receptors and KIR2DL2 alleles encoding strong inhibitory C1 receptors. The wide-ranging properties of KIR allotypes arise from substitutions throughout the KIR molecule. Such substitutions can influence cell surface expression, as well as the avidity and specificity for HLA-C ligands. Consistent with the crucial role of inhibitory HLA-C receptors in self-recognition, as well as NK cell education and response, most KIR haplotypes have both a functional C1 and C2 receptor, despite the considerable variation that occurs in ligand recognition and surface expression.
PMID: 26311903 [PubMed - as supplied by publisher]
IgH sequences in common variable immune deficiency reveal altered B cell development and selection.
Sci Transl Med. 2015 Aug 26;7(302):302ra135
Authors: Roskin KM, Simchoni N, Liu Y, Lee JY, Seo K, Hoh RA, Pham T, Park JH, Furman D, Dekker CL, Davis MM, James JA, Nadeau KC, Cunningham-Rundles C, Boyd SD
Common variable immune deficiency (CVID) is the most common symptomatic primary immune deficiency, affecting ~1 in 25,000 persons. These patients suffer from impaired antibody responses, autoimmunity, and susceptibility to lymphoid cancers. To explore the cellular basis for these clinical phenotypes, we conducted high-throughput DNA sequencing of immunoglobulin heavy chain gene rearrangements from 93 CVID patients and 105 control subjects and sorted naïve and memory B cells from 13 of the CVID patients and 10 of the control subjects. The CVID patients showed abnormal VDJ rearrangement and abnormal formation of complementarity-determining region 3 (CDR3). We observed a decreased selection against antibodies with long CDR3s in memory repertoires and decreased variable gene replacement, offering possible mechanisms for increased patient autoreactivity. Our data indicate that patient immunodeficiency might derive from both decreased diversity of the naïve B cell pool and decreased somatic hypermutation in memory repertoires. The CVID patients also exhibited an abnormal clonal expansion of unmutated B cells relative to the controls. Although impaired B cell germinal center activation is commonly viewed as causative in CVID, these data indicate that CVID B cells diverge from controls as early as the pro-B stage, cell and suggest possible explanations for the increased incidence of autoimmunity, immunodeficiency, and lymphoma CVID patients.
PMID: 26311730 [PubMed - as supplied by publisher]
Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design.
Int J Stroke. 2015 Aug 26;
Authors: Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Held P, Jonasson J, Minematsu K, Molina CA, Wong LK
RATIONALE: The risk of recurrent ischemia is high in the acute period after ischemic stroke and transient ischemic attack. Aspirin is recommended by guidelines for this indication, but more intensive antiplatelet therapy may be justified.
AIMS: We aim to evaluate whether ticagrelor, a potent antiplatelet agent that blocks the P2Y12 receptor without requiring metabolic activation, reduces the risk of major vascular events compared with aspirin when randomization occurs within 24 h after symptom onset of a nonsevere ischemic stroke or high-risk transient ischemic attack.
DESIGN: Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) is a randomized, double-blind, event-driven trial and will include an estimated 13 600 participants randomized in 33 countries worldwide to collect 844 primary events.
STUDY OUTCOMES: The primary endpoint is the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first primary endpoint will be compared in the treatment groups during 90-day follow-up, with major hemorrhage serving as the primary safety endpoint. Participants will be followed for an additional 30 days after the randomized treatment period.
DISCUSSION: The SOCRATES trial fulfills an important clinical need by evaluating a potent antiplatelet agent as a superior alternative to current standard of care in patients presenting acutely with ischemic stroke or transient ischemic attack.
PMID: 26311628 [PubMed - as supplied by publisher]
State of the art systematic review of bone disease in anorexia nervosa.
Int J Eat Disord. 2015 Aug 27;
Authors: Misra M, Golden NH, Katzman DK
OBJECTIVE: Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management.
METHOD: Search terms included "anorexia nervosa" AND "bone density" for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995.
RESULTS: AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN.
DISCUSSION: To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015).
PMID: 26311400 [PubMed - as supplied by publisher]
MLL leukemia induction by genome editing of human CD34+ hematopoietic cells.
Blood. 2015 Aug 26;
Authors: Buechele C, Breese EH, Schneidawind D, Lin CH, Jeong J, Duque-Afonso J, Wong SH, Smith KS, Negrin RS, Porteus M, Cleary ML
Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene occur in primary and treatment-related leukemias, and confer a poor prognosis. Studies based primarily on mouse models have substantially advanced our understanding of MLL leukemia pathogenesis, but often employ supra-physiologic oncogene expression with uncertain implications for human leukemia. Genome editing using site-specific nucleases provides a powerful new technology for gene modification to potentially model human disease, however this approach has not been used to recreate acute leukemia in human cells of origin comparable to disease observed in patients. We applied TALEN-mediated genome editing to generate endogenous MLL-AF9 and MLL-ENL oncogenes through insertional mutagenesis in primary human hematopoietic stem and progenitor cells (HSPCs) derived from human umbilical cord blood. Engineered HSPCs displayed altered in vitro growth potentials and induced acute leukemias following transplantation in immuno-compromised mice at a mean latency of 16 weeks. The leukemias displayed phenotypic and morphologic similarities with patient leukemia blasts including a subset with mixed phenotype, a distinctive feature seen in clinical disease. The leukemic blasts expressed an MLL-associated transcriptional program with elevated levels of crucial MLL target genes, displayed heightened sensitivity to DOT1L inhibition, and demonstrated increased oncogenic potential ex vivo and in secondary transplant assays. Thus, genome editing to create endogenous MLL oncogenes in primary human HSPCs faithfully models acute MLL-rearranged leukemia and provides an experimental platform for prospective studies of leukemia initiation and stem cell biology in a genetic subtype of poor prognosis leukemia.
PMID: 26311362 [PubMed - as supplied by publisher]
The role of passive avian head stabilization in flapping flight.
J R Soc Interface. 2015 Sep 6;12(110)
Authors: Pete AE, Kress D, Dimitrov MA, Lentink D
Birds improve vision by stabilizing head position relative to their surroundings, while their body is forced up and down during flapping flight. Stabilization is facilitated by compensatory motion of the sophisticated avian head-neck system. While relative head motion has been studied in stationary and walking birds, little is known about how birds accomplish head stabilization during flapping flight. To unravel this, we approximate the avian neck with a linear mass-spring-damper system for vertical displacements, analogous to proven head stabilization models for walking humans. We corroborate the model's dimensionless natural frequency and damping ratios from high-speed video recordings of whooper swans (Cygnus cygnus) flying over a lake. The data show that flap-induced body oscillations can be passively attenuated through the neck. We find that the passive model robustly attenuates large body oscillations, even in response to head mass and gust perturbations. Our proof of principle shows that bird-inspired drones with flapping wings could record better images with a swan-inspired passive camera suspension.
PMID: 26311316 [PubMed - as supplied by publisher]
Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients.
Nephrol Dial Transplant. 2015 Aug 26;
Authors: Airy M, Mandayam S, Mitani AA, Chang TI, Ding VY, Brookhart MA, Goldstein BA, Winkelmayer WC
BACKGROUND: Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD).
METHODS: Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)].
RESULTS: In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups.
CONCLUSIONS: In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.
PMID: 26311216 [PubMed - as supplied by publisher]
Parsing Physiological Functions of Erythropoietin One Domain at a Time.
Neurotherapeutics. 2015 Aug 27;
Authors: Steinman L
A domain of erythropoietin (EPO), separate from the domain involved in red blood cell development, has been identified. This region of EPO has anti-inflammatory and neuroprotective effects. Use of a peptide sequence from this region provides the potential for an effective therapeutic without effects on erythropoiesis.
PMID: 26311151 [PubMed - as supplied by publisher]
Twist-drill craniotomy for the treatment of chronic subdural hematomas and the use of the pre-coronal suture entry point.
Clin Neurol Neurosurg. 2015 Aug 14;
Authors: Jung H, Shah A
PMID: 26310947 [PubMed - as supplied by publisher]
Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.
Sci Rep. 2015;5:13476
Authors: Zilbermintz L, Leonardi W, Jeong SY, Sjodt M, McComb R, Ho CC, Retterer C, Gharaibeh D, Zamani R, Soloveva V, Bavari S, Levitin A, West J, Bradley KA, Clubb RT, Cohen SN, Gupta V, Martchenko M
A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.
PMID: 26310922 [PubMed - as supplied by publisher]
Risk of Nonspine Fractures in Older Adults with Sarcopenia, Low Bone Mass, or Both.
J Am Geriatr Soc. 2015 Aug 27;
Authors: Chalhoub D, Cawthon PM, Ensrud KE, Stefanick ML, Kado DM, Boudreau R, Greenspan S, Newman AB, Zmuda J, Orwoll ES, Cauley JA, Osteoporotic Fractures in Men Study Research Group
OBJECTIVES: To test the hypothesis that men and women with low bone mineral density (BMD) and sarcopenia have a higher risk of fracture than those with only one or neither conditions.
DESIGN: The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospective observational studies with a mean follow up of 9 (2000-2012) and 8 years (1997-2009), respectively.
SETTING: U.S. clinical centers.
PARTICIPANTS: Men (n = 5,544; mean age 73.7) and women (n = 1,114; mean age 77.6) aged 65 and older, able to walk without assistance, and without bilateral hip replacement.
MEASUREMENTS: Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0. Participants were classified as having normal BMD and no sarcopenia (3,367 men, 308 women), sarcopenia only (79 men, 48 women), low BMD only (1,986 men, 626 women), and low BMD and sarcopenia (112 men, 132 women).
RESULTS: Men with low BMD and sarcopenia (hazard ratio (HR)=3.79, 95% confidence interval (CI)=2.65-5.41) and men with low BMD only (HR=1.67, 95% CI=1.45-1.93) but not men with sarcopenia only (HR=1.14, 95% CI=0.62-2.09) had greater risk of fracture than men with normal BMD and no sarcopenia. Women with low BMD and sarcopenia (HR=2.27, 95% CI=1.37-3.76) and women with low BMD alone (HR=2.62, 95% CI=1.74-3.95), but not women with only sarcopenia, had greater risk of fracture than women with normal BMD and no sarcopenia.
CONCLUSION: Men with low BMD and sarcopenia are at especially high risk of fracture. Sarcopenia alone did not increase fracture risk in either group.
PMID: 26310882 [PubMed - as supplied by publisher]
An immunological view of chemotherapy.
Immunotherapy. 2015 Aug 27;
Authors: Tsung K, Norton JA
PMID: 26310824 [PubMed - as supplied by publisher]
Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.
Brain. 2015 Aug 25;
Authors: Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME, Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC)
We aimed to characterize genotype-phenotype correlations and establish baseline clinical data for peripheral neuropathies caused by mutations in the myelin protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot-Marie-Tooth disease type 1. Recent research makes clinical trials for patients with MPZ mutations a realistic possibility. However, the clinical severity varies with different mutations and natural history data on progression is sparse. We present cross-sectional data to begin to define the phenotypic spectrum and clinical baseline of patients with these mutations. A cohort of patients with MPZ gene mutations was identified in 13 centres of the Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009 and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments. Genetic testing was performed in all patients and/or in first- or second-degree relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie-Tooth disease type 1B. There were 103 patients from 71 families with 47 different MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and mutations were separated into infantile, childhood and adult-onset groups. The infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and slower nerve conductions than the other groups, and severity increased with age. Twenty-three patients had no family history of Charcot-Marie-Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking assistance or support, and 10 required wheelchairs. There was hearing loss in 21 and scoliosis in 17. Forty-two patients did not begin walking until after 15 months of age. Half of the infantile onset patients then required ambulation aids or wheelchairs for ambulation. Our results demonstrate that virtually all MPZ mutations are associated with specific phenotypes. Early onset (infantile and childhood) phenotypes likely represent developmentally impaired myelination, whereas the adult-onset phenotype reflects axonal degeneration without antecedent demyelination. Data from this cohort of patients will provide the baseline data necessary for clinical trials of patients with Charcot-Marie-Tooth disease caused by MPZ gene mutations.
PMID: 26310628 [PubMed - as supplied by publisher]
Association of worker characteristics and early reimbursement for physical therapy, chiropractic and opioid prescriptions with workers' compensation claim duration, for cases of acute low back pain: an observational cohort study.
BMJ Open. 2015;5(8):e007836
Authors: Busse JW, Ebrahim S, Heels-Ansdell D, Wang L, Couban R, Walter SD
OBJECTIVE: To assess the association between early reimbursement for physiotherapy, chiropractic and opioid prescriptions for acute low back pain (LBP) with disability claim duration.
DESIGN: Observational cohort study.
SETTING AND PARTICIPANTS: From a random sample of 6665 claims for acute, uncomplicated LBP approved by the Ontario Workplace Safety and Insurance Board (WSIB) in 2005, we analysed 1442 who remained on full benefits at 4 weeks after claim approval.
PRIMARY OUTCOME MEASURE: Our primary outcome was WSIB claim duration.
RESULTS: We had complete data for all but 3 variables, which had <15% missing data, and we included missing data as a category for these factors. Our time-to-event analysis was adjusted for demographic, workplace and treatment factors, but not injury severity, although we attempted to include a sample with very similar, less-severe injuries. Regarding significant factors and treatment variables in our adjusted analysis, older age (eg, HR for age ≥55 vs <25=0.52; 99% CI 0.36 to 0.74) and WSIB reimbursement for opioid prescription in the first 4 weeks of a claim (HR=0.68; 99% CI 0.53 to 0.88) were associated with longer claim duration. Higher predisability income was associated with longer claim duration, but only among persistent claims (eg, HR for active claims at 1 year with a predisability income >$920 vs ≤$480/week=0.34; 99% CI 0.17 to 0.68). Missing data for union membership (HR=1.27; 99% CI 1.01 to 1.59), and working for an employer with a return-to-work programme were associated with fewer days on claim (HR=1.78; 99% CI 1.45 to 2.18). Neither reimbursement for physiotherapy (HR=1.01; 99% CI 0.86 to 1.19) nor chiropractic care (HR for active claims at 60 days=1.15; 99% CI 0.94 to 1.41) within the first 4 weeks was associated with claim duration. Our meta-analysis of 3 studies (n=51 069 workers) confirmed a strong association between early opioid use and prolonged claim duration (HR=0.57, 95% CI 0.48 to 0.69; low certainty evidence).
CONCLUSIONS: Our analysis found that early WSIB reimbursement for physiotherapy or chiropractic care, in claimants fully off work for more than 4 weeks, was not associated with claim duration, and that early reimbursement for opioids predicted prolonged claim duration. Well-designed randomised controlled trials are needed to verify our findings and establish causality between these variables and claim duration.
PMID: 26310398 [PubMed - as supplied by publisher]
Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.
Transl Oncol. 2015 Aug;8(4):239-249
Authors: Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KY
BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients.
MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs.
RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup.
CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.
PMID: 26310369 [PubMed - as supplied by publisher]
CMV after transplant: T-cell repertoire crooks.
Blood. 2015 Jun 18;125(25):3827-8
Authors: Meyer E
PMID: 26089376 [PubMed - indexed for MEDLINE]
Exosomes as potential alternatives to stem cell therapy in mediating cardiac regeneration.
Circ Res. 2015 Jun 19;117(1):7-9
Authors: Ong SG, Wu JC
PMID: 26089361 [PubMed - indexed for MEDLINE]
Risk of Next Melanoma in Patients With Familial and Sporadic Melanoma by Number of Previous Melanomas.
JAMA Dermatol. 2015 Jun;151(6):607-15
Authors: Chen T, Fallah M, Försti A, Kharazmi E, Sundquist K, Hemminki K
IMPORTANCE: The risk of next melanoma in patients with 2 or more previous melanomas stratified by familial and sporadic cases separately has not yet been reported, although a few population-based studies have assessed the risk of second melanoma.
OBJECTIVE: To assess the risk of next melanoma in patients with multiple primary melanomas by number of previous melanomas, stratified by demographic and melanoma characteristics.
DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study with follow-up from 1958 to 2010 using the Swedish Family-Cancer Database with information on cancer cases retrieved from the Swedish Cancer Registry. A total of 65,429 patients with invasive or in situ melanoma who received a diagnosis during 1958 through 2010 were observed for next melanoma incidence.
MAIN OUTCOMES AND MEASURES: Standardized incidence ratios (SIRs) expressing risk of next melanoma by calculating the incidence of next (second, third, fourth, and fifth) melanoma in melanoma patients who had received a diagnosis of 1, 2, 3, and 4, respectively, previous melanomas, compared with the risk of first melanoma in the Swedish population.
RESULTS: For patients with either familial or sporadic melanoma, we observed a stable 2- to 3-times elevated risk by increasing number of previous melanomas; for example, for 2 previous melanomas, the SIR was 2.8 (95% CI, 2.3-3.4) for patients with familial melanoma and 2.5 (95% CI, 2.3-2.7) for patients with sporadic melanoma. Overall risk of second melanoma was higher in patients with familial melanoma who received a diagnosis at younger than 40 years (SIR, 4.7 [95% CI, 3.9-5.6]), and we found a notable risk in young patients with familial melanoma during the first 5-year follow-up after first melanoma: SIR of 6.1 (95% CI, 4.0-9.0) for interval up to 1 year, 6.2 (95% CI, 3.2-11) for 2 to 3 years, and 19 (95% CI, 10-31) for 4 to 5 years. Risk was notable in young (<40 years) patients with sporadic melanoma within the first year of follow-up (SIR, 5.3 [95% CI, 4.3-6.4]) and afterward remained steadily elevated by 2 to 3 times.
CONCLUSIONS AND RELEVANCE: We found a stable 2- to 3-times elevated risk by number of previous melanomas for patients with either familial or sporadic melanoma. Notable risk in young patients with familial melanoma during first 5-year follow-up after first melanoma may suggest that it is important to refer these patients for clinical genetic testing.
PMID: 25671687 [PubMed - indexed for MEDLINE]
Multilocus adaptation associated with heat resistance in reef-building corals.
Curr Biol. 2014 Dec 15;24(24):2952-6
Authors: Bay RA, Palumbi SR
The evolution of tolerance to future climate change depends on the standing stock of genetic variation for resistance to climate-related impacts, but genes contributing to climate tolerance in wild populations are poorly described in number and effect. Physiology and gene expression patterns have shown that corals living in naturally high-temperature microclimates are more resistant to bleaching because of both acclimation and fixed effects, including adaptation. To search for potential genetic correlates of these fixed effects, we genotyped 15,399 single nucleotide polymorphisms (SNPs) in 23 individual tabletop corals, Acropora hyacinthus, within a natural temperature mosaic in backreef lagoons on Ofu Island, American Samoa. Despite overall lack of population substructure, we identified 114 highly divergent SNPs as candidates for environmental selection, via multiple stringent outlier tests, and correlations with temperature. Corals from the warmest reef location had higher minor allele frequencies across these candidate SNPs, a pattern not seen for noncandidate loci. Furthermore, within backreef pools, colonies in the warmest microclimates had a higher number and frequency of alternative alleles at candidate loci. These data suggest mild selection for alternate alleles at many loci in these corals during high heat episodes and possible maintenance of extensive polymorphism through multilocus balancing selection in a heterogeneous environment. In this case, a natural population harbors a reservoir of alleles preadapted to high temperatures, suggesting potential for future evolutionary response to climate change.
PMID: 25454780 [PubMed - indexed for MEDLINE]
Urine drug screening: opioid risks preclude complete patient autonomy.
Pain Med. 2014 Dec;15(12):2001-2
Authors: Darnall BD, Schatman ME
PMID: 25376661 [PubMed - indexed for MEDLINE]
Urine drug screening: necessary or alienating?
Pain Med. 2014 Dec;15(12):1999
Authors: Darnall BD, Schatman ME
PMID: 25376375 [PubMed - indexed for MEDLINE]
Intraoperative neuromonitoring for superior semicircular canal dehiscence and hearing outcomes.
Otol Neurotol. 2015 Jan;36(1):139-45
Authors: Wenzel A, Ward BK, Ritzl EK, Gutierrez-Hernandez S, Della Santina CC, Minor LB, Carey JP
BACKGROUND: Recent findings in patients with superior semicircular canal dehiscence (SCD) have shown an elevated ratio of summating potential (SP) to action potential (AP), as measured by electrocochleography (ECochG). Changes in this ratio can be seen during surgical intervention. The objective of this study was to evaluate the utility of intraoperative ECochG and auditory brainstem response (ABR) as predictive tools for postoperative hearing outcomes after surgical plugging via middle cranial fossa approach for SCD syndrome (SCDS).
METHODS: This was a review of 34 cases (33 patients) in which reproducible intraoperative ECochG recordings were obtained during surgery. Diagnosis of SCDS was based on history, physical examination, vestibular function testing, and computed tomography imaging. Simultaneous intraoperative ECochG and ABR were performed. Pure-tone audiometry was performed preoperatively and at least 1 month postoperatively, and air-bone gap (ABG) was calculated. Changes in SP/AP ratio, SP amplitude, and ABR wave I latency were compared with changes in pure-tone average and ABG before and after surgery.
RESULTS: Median SP/AP ratio of affected ears was 0.62 (interquartile range [IQR], 0.45-0.74) and decreased immediately after surgical plugging of the affected canal to 0.42 (IQR, 0.29-0.52; p < 0.01). Contralateral SP/AP ratio before plugging was 0.33 (IQR, 0.25-0.42) and remained unchanged at the conclusion of surgery (0.30; IQR, 0.25-0.35; p = 0.32). Intraoperative changes in ABR wave I latency and SP amplitude did not predict changes in pure-tone average or ABG after surgery (p > 0.05).
CONCLUSION: This study confirmed the presence of an elevated SP/AP ratio in ears with SCDS. The SP/AP ratio commonly decreases during plugging. However, an intraoperative decrease in SP/AP does not appear to be sensitive to either the beneficial decrease in ABGs or the mild high-frequency sensory loss that can occur in patients undergoing surgical plugging of the superior semicircular canal. Future work will determine the value of intraoperative ECochG in predicting changes in vestibular function.
PMID: 25333320 [PubMed - indexed for MEDLINE]
Illuminating circuitry relevant to psychiatric disorders with optogenetics.
Curr Opin Neurobiol. 2015 Feb;30:9-16
Authors: Steinberg EE, Christoffel DJ, Deisseroth K, Malenka RC
The brain's remarkable capacity to generate cognition and behavior is mediated by an extraordinarily complex set of neural interactions that remain largely mysterious. This complexity poses a significant challenge in developing therapeutic interventions to ameliorate psychiatric disease. Accordingly, few new classes of drugs have been made available for patients with mental illness since the 1950s. Optogenetics offers the ability to selectively manipulate individual neural circuit elements that underlie disease-relevant behaviors and is currently accelerating the pace of preclinical research into neurobiological mechanisms of disease. In this review, we highlight recent findings from studies that employ optogenetic approaches to gain insight into normal and aberrant brain function relevant to mental illness. Emerging data from these efforts offers an exquisitely detailed picture of disease-relevant neural circuits in action, and hints at the potential of optogenetics to open up entirely new avenues in the treatment of psychiatric disorders.
PMID: 25215625 [PubMed - indexed for MEDLINE]
The combined subtemporal-transfacial approach for the resection of juvenile nasopharyngeal angiofibromas with intracranial extension.
Otol Neurotol. 2015 Jan;36(1):151-5
Authors: Kumar AR, Nayak JV, Janisiewicz AM, Li G, Oghalai JS
OBJECTIVE: Stage IVb juvenile nasopharyngeal angiofibromas (JNAs) are frequently regarded as unresectable because of their intracranial extension and cavernous sinus invasion. Although radiation has been described to control these tumors, it can leave the adolescent with long-lasting sequelae. Herein, we describe an alternative treatment strategy based on a combined subtemporal-transfacial surgical approach that permits the successful management of advanced stage JNAs by divorcing the intracranial vascular supply to these massive lesions.
PATIENTS: Four male patients were identified with Andrew's Stage IVB JNAs.
INTERVENTION: All patients were treated by surgical resection using a combined subtemporal-transfacial surgical approach.
MAIN OUTCOME MEASURES: Parameters assessed included tumor extent, number and types of surgical procedures, extent of resections, complications, and recurrence rate.
RESULTS: Near-total tumor resections were achieved in all patients. No cerebrospinal fluid leak or cranial neuropathies were noted. All but one patient had local recurrences, and these could be managed with repetitive endoscopic debridement. No patient required adjuvant radiation treatment to control advanced disease.
CONCLUSIONS: With the use of modern skull base surgical techniques, coordinated interdisciplinary care, and safe, near-total removal of the tumor mass, adolescent males with advanced JNAs may be spared the long-term morbidities associated with using radiation to treat these benign but aggressive lesions.
PMID: 25036780 [PubMed - indexed for MEDLINE]
Reasoning based quality assurance of medical ontologies: a case study.
AMIA Annu Symp Proc. 2014;2014:671-80
Authors: Horridge M, Parsia B, Noy NF, Musenm MA
The World Health Organisation is using OWL as a key technology to develop ICD-11 - the next version of the well-known International Classification of Diseases. Besides providing better opportunities for data integration and linkages to other well-known ontologies such as SNOMED-CT, one of the main promises of using OWL is that it will enable various forms of automated error checking. In this paper we investigate how automated OWL reasoning, along with a Justification Finding Service can be used as a Quality Assurance technique for the development of large and complex ontologies such as ICD-11. Using the International Classification of Traditional Medicine (ICTM) - Chapter 24 of ICD-11 - as a case study, and an expert panel of knowledge engineers, we reveal the kinds of problems that can occur, how they can be detected, and how they can be fixed. Specifically, we found that a logically inconsistent version of the ICTM ontology could be repaired using justifications (minimal entailing subsets of an ontology). Although over 600 justifications for the inconsistency were initially computed, we found that there were three main manageable patterns or categories of justifications involving TBox and ABox axioms. These categories represented meaningful domain errors to an expert panel of ICTM project knowledge engineers, who were able to use them to successfully determine the axioms that needed to be revised in order to fix the problem. All members of the expert panel agreed that the approach was useful for debugging and ensuring the quality of ICTM.
PMID: 25954373 [PubMed - indexed for MEDLINE]
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