Quality of Care in Humanitarian Surgery

Humanitarian surgical programs are set up de novo, within days or hours in emergency or disaster settings. In such circumstances, insuring quality of care is extremely challenging. Basic structural inputs such as a safe structure, electricity, clean water, a blood bank, sterilization equipment, a post-anesthesia recovery unit, appropriate medications should be established. Currently, no specific credentials are needed for surgeons to operate in a humanitarian setting; the training of more humanitarian surgeons is desperately needed. Standard perioperative protocols for the humanitarian setting after common procedures such as Cesarean section, burn care, open fractures, and amputations and antibiotic prophylaxis, and post-operative pain management must be developed. Outcome data, especially long-term outcomes, are difficult to collect as patients often do not return for follow-up and may be difficult to trace; standard databases for post-operative infections and mortality rates should be established. Checklists have recently received significant attention as an instrument to support the improvement of surgical quality; knowing which items are most applicable to humanitarian settings remains unknown. In conclusion, the quality of surgical services in humanitarian settings must be regulated. Many other core medical activities of humanitarian organizations such as therapeutic feeding, mass vaccination, and the treatment of infectious diseases, such as tuberculosis and human immunodeficiency virus, are subject to rigorous reporting of quality indicators. There is no reason why surgery should be exempted from quality oversight. The surgical humanitarian community should pull together before the next disaster strikes

Variations and inter-relationship in outcome from emergency admissions in England: a retrospective analysis of Hospital Episode Statistics from 2005-2010.

BACKGROUND: The quality of care delivered and clinical outcomes of care are of paramount importance. Wide variations in the outcome of emergency care have been suggested, but the scale of variation, and the way in which outcomes are inter-related are poorly defined and are critical to understand how best to improve services. This study quantifies the scale of variation in three outcomes for a contemporary cohort of patients undergoing emergency medical and surgical admissions. The way in which the outcomes of different diagnoses relate to each other is investigated. METHODS: A retrospective study using the English Hospital Episode Statistics 2005-2010 with one-year follow-up for all patients with one of 20 of the commonest and highest-risk emergency medical or surgical conditions. The primary outcome was in-hospital all-cause risk-standardised mortality rate (in-RSMR). Secondary outcomes were 1-year all-cause risk-standardised mortality rate (1 yr-RSMR) and 28-day all-cause emergency readmission rate (RSRR). RESULTS: 2,406,709 adult patients underwent emergency medical or surgical admissions in the groups of interest. Clinically and statistically significant variations in outcome were observed between providers for all three outcomes (p < 0.001). For some diagnoses including heart failure, acute myocardial infarction, stroke and fractured neck of femur, more than 20% of hospitals lay above the upper 95% control limit and were statistical outliers. The risk-standardised outcomes within a given hospital for an individual diagnostic group were significantly associated with the aggregated outcome of the other clinical groups. CONCLUSIONS: Hospital-level risk-standardised outcomes for emergency admissions across a range of specialties vary considerably and cross traditional speciality boundaries. This suggests that global institutional infra-structure and processes of care influence outcomes. The implications are far reaching, both in terms of investigating performance at individual hospitals and in understanding how hospitals can learn from the best performers to improve outcomes

JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement.

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

<p>Abstract</p> <p>Background</p> <p>Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems.</p> <p>Methods</p> <p>Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol.</p> <p>Results</p> <p>All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed.</p> <p>Conclusion</p> <p>NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.</p

Checkpoint Signaling, Base Excision Repair, and PARP Promote Survival of Colon Cancer Cells Treated with 5-Fluorodeoxyuridine but Not 5-Fluorouracil

The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor

Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

<p>Abstract</p> <p>Background</p> <p>The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation.</p> <p>Methods</p> <p>UVB-irradiated p53^+/-mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling.</p> <p>Results</p> <p>UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19⁺, CD5⁺, B220⁺, IgM⁺and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression.</p> <p>Conclusion</p> <p>UV-irradiated p53^+/-mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The induction of B cell lymphoma in UV-irradiated p53 heterozygous mice may provide a useful model for lymphoma development in humans.</p

Internal Ribosomal Entry Site-Mediated Translation Is Important for Rhythmic PERIOD1 Expression

The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES) in the 5′ untranslated region (UTR). Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5′UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes

The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells

Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), and increased the ratio of female to male fish (22 µg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHß, INHα, αGSU, and 11ß-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates