PATH (Performance Assessment Tool for Quality Improvement in Hospitals), a project of the World Health Organization (WHO) for Europe offers hospitals a comprehensive and standardized tool (a set of ...indicators) to evaluate their own performance and development of measures for quality improvement. PATH Program was launched in Croatia in 2008, and it was conducted in 2009 in hospitals that have voluntarily decided to be involved. Here we present the results of the first phase of pilot experience of establishing the program, based on data collected in 22 Croatian hospitals. Analysis of the first results indicated the existence of marked differences among the hospitals that have taken the example of the percentage of cesarean sections ranging from 1.1% to 21.4%. The mortality rate of myocardial infarction ranged from 1.9 to 21.4%, while the mortality of stroke ranged from 12.5 to 45.5%. The highest percentage of needle-stick injuries reported for physicians was 16.2% of entire hospital staff in one year, 6.1% for nurses and 4.6% for the supportive staff. The result suggests the existence of many problems and limitations in data collection at hospital level, limitations in their analysis and creates recommendations for quality improvements, which must be taken into account when hospitals are compared on the national or international level.
Za vrijeme srpske agresije Opća bolnica u Vinkovcima podnijela je veliki teret i postala prava ratna bolnica uz prvu liniju bojišnice. U sklopu rada kirurške ekipe radila je i ORL-služba prilikom ...zbrinjavanja ratnih ozljeda glave i vrata. Brojne manje ozljede i traumatska oštećenja sluha, kao i eksplozivne ozljede bubnjića, nisu ovdje prikazane, jer u tijeku žestokog rata nisu sve bile niti evidentirane. Prikazali smo 107 ranjenika sa ozljedama ORL-regije, koji su upisani u veliki operacijski protokol, koje smo zbrinuli za vrijeme Domovinskog rata 1991/92. godine. Najveći broj ozljeda ORL-regije je u nas i definitivno zbrinut, dok su evakuacije u druge zdravstvene ustanove uslijedile zbog opće teške ratne situacije i prijetnje od potpunog okruženja grada.
PATH (Performance Assessment Tool for Quality Improvement in Hospitals), projekt Regionalnog ureda Svjetske zdravstvene organizacije (SZO) za Europu pruža bolnicama sveobuhvatan i standardiziran alat ...za vrednovanje vlastitih rezultata i razvoj mjera za unapređenje kvalitete. Program PATH pokrenut je 2008. godine i u Hrvatskoj, a od 2009. godine provodi se u bolnicama koje su se dobrovoljno odlučile u njega uključiti. U ovom radu prikazujemo prva iskustva probne faze uspostavljanja programa PATH, utemeljena na podacima koji su prikupljani u 22 hrvatske bolnice. Analiza prvih rezultata upozorila je na postojanje izraženih razlika među bolnicama, koje su se na primjeru postotka carskih rezova kretale od najmanje 1,1% do najviše 21,4% zabilježenih carskih rezova u pojedinim bolnicama tijekom razdoblja prikupljanja podataka. Stopa smrtnosti infarkta miokarda kretala se od 1,9 do 21,4%, dok se smrtnost moždanog udara kretala od 12,5 do 45,5%. Najviši postotak prijavljenih ubodnih ozljeda za liječnike iznosio je 16,2% osoblja tijekom jedne godine, 6,1% za medicinske sestre i 4,6% za spremačice. Ovo istraživanje upućuje na postojanje mnogih problema i ograničenja u prikupljanju pokazatelja na bolničkoj razini, njihovoj analizi i stvaranju preporuka za unapređenje kvalitete koje se moraju uzeti u obzir prilikom usporedbe bolnica na nacionalnoj ili međunarodnoj razini.
•This study sheds light on how customer trust repair occurs.•We investigate factors and conditions associated with trust recovery in a retailer.•Four factors and three contextual conditions are ...associated with trust recovery.•Trust recovery is not necessarily a direct result of a trustee’s repair activities.
Although in recent years academic interest in trust repair following a breach has grown significantly, we still know very little about how trust repair happens and in what contexts. This study focuses on customer trust repair following a major food adulteration scandal. Through a grounded theory study of customer experiences of real-life trust breakdown and recovery, we identify four factors (absence of further transgressions, positive personal experience with the retailer, the retailer’s normal functioning, and the normal behavior of other customers) and three contextual conditions (passage of time, institutional context, and immediate trust repair strategies) associated with customers’ trust recovery in food retailers. In addition, we show that trust recovery is not necessarily a direct result of the trustee’s trust repair activities, as theorized previously, before discussing the implications of our findings for theory and practice.
Targeted therapies provide an exciting new approach to combat human cancer. The immediate effect is a dramatic reduction in disease burden, but in most cases, the tumor returns as a consequence of ...resistance. Various mechanisms for the evolution of resistance have been implicated, including mutation of target genes and activation of other drivers. There is increasing evidence that the reason for failure of many targeted treatments is a small preexisting subpopulation of resistant cells; however, little is known about the genetic composition of this resistant subpopulation. Using the novel approach of ordering the resistant subclones according to their time of appearance, here we describe the full spectrum of resistance mutations present in a metastatic lesion. We calculate the expected and median number of cells in each resistant subclone. Surprisingly, the ratio of the medians of successive resistant clones is independent of any parameter in our model; for example, the median of the second clone divided by the median of the first is Formula. We find that most radiographically detectable lesions harbor at least 10 resistant subclones. Our predictions are in agreement with clinical data on the relative sizes of resistant subclones obtained from liquid biopsies of colorectal cancer patients treated with epidermal growth factor receptor (EGFR) blockade. Our theory quantifies the genetic heterogeneity of resistance that exists before treatment and provides information to design treatment strategies that aim to control resistance.
Significance Metastatic dissemination to surgically inaccessible sites is the major cause of death in cancer patients. Targeted therapies, often initially effective against metastatic disease, invariably fail due to resistance. We use mathematical modeling to study heterogeneity of resistance to treatment and describe for the first time, to our knowledge, the entire ensemble of resistant subclones present in metastatic lesions. We show that radiographically detectable metastatic lesions harbor multiple resistant subclones of comparable size and compare our predictions to clinical data on resistance-associated mutations in colorectal cancer patients. Our model provides important information for the development of second-line treatments that aim to inhibit known resistance mutations.
Autori su opisali svoja zapažanja na 82 bolesnika s produženom orotrahealnom intubacijom, od 1 do 8 dana. Prikazana je učestalost uočljivih simptoma (promuklost, disfagija, dispneja), intenzitet ...oštećenja sluznice larinksa, te lokalizacije lezija obzirom na dužinu trajanja intubacije. Postmortalni nalaz 35 pregledanih larinksa bio je u skladu s kliničkim nalazom. Produženjem trajanja intubacije, uz lezije glotisa, oš tećenja zahvaćaju supraglotis a kasnije i subglotis. Unatoč tomu, produžena orotrahealna intubacija predstavlja jednu od metoda liječenja bolesnika s akutnim respiratornim insuficijencijama.
In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance ...is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. DOI:http://dx.doi.org/10.7554/eLife.00747.001.
Assessment of measurable residual disease (MRD) upon treatment of acute myeloid leukemia (AML) remains challenging. It is usually addressed by highly sensitive PCR- or sequencing-based screening of ...specific mutations, or by multiparametric flow cytometry. However, not all patients have suitable mutations and heterogeneity of surface markers hampers standardization in clinical routine. In this study, we propose an alternative approach to estimate MRD based on AML-associated DNA methylation (DNAm) patterns. We identified four CG dinucleotides (CpGs) that commonly reveal aberrant DNAm in AML and their combination could reliably discern healthy and AML samples. Interestingly, bisulfite amplicon sequencing demonstrated that aberrant DNAm patterns were symmetric on both alleles, indicating that there is epigenetic crosstalk between homologous chromosomes. We trained shallow-learning and deep-learning algorithms to identify anomalous DNAm patterns. The method was then tested on follow-up samples with and without MRD. Notably, even samples that were classified as MRD negative often revealed higher anomaly ratios than healthy controls, which may reflect clonal hematopoiesis. Our results demonstrate that targeted DNAm analysis facilitates reliable discrimination of malignant and healthy samples. However, since healthy samples also comprise few abnormal-classified DNAm reads the approach does not yet reliably discriminate MRD positive and negative samples.
Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this ...acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6 months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
The use of large-scale national databases for observational research in orthopaedic surgery has grown substantially in the last decade, and the data sets can be grossly categorized as either ...administrative claims or clinical registries. Administrative claims data comprise the billing records associated with the delivery of health-care services. Orthopaedic researchers have used both government and private claims to describe temporal trends, geographic variation, disparities, complications, outcomes, and resource utilization associated with both musculoskeletal disease and treatment. Medicare claims comprise one of the most robust data sets used to perform orthopaedic research, with >45 million beneficiaries. The U.S. government, through the Centers for Medicare & Medicaid Services, often uses these data to drive changes in health policy. Private claims data used in orthopaedic research often comprise more heterogeneous patient demographic samples, but allow longitudinal analysis similar to that offered by Medicare claims. Discharge databases, such as the U.S. National Inpatient Sample, provide a wide national sampling of inpatient hospital stays from all payers and allow analysis of associated adverse events and resource utilization. Administrative claims data benefit from the high patient numbers obtained through a majority of hospitals. Using claims, it is possible to follow patients longitudinally throughout encounters irrespective of the location of the institution delivering health care. Some disadvantages include lack of precision of ICD-9 (International Classification of Diseases, Ninth Revision) coding schemes. Much of these data are expensive to purchase, complicated to organize, and labor-intensive to manipulate--often requiring trained specialists for analysis. Given the changing health-care environment, it is likely that databases will provide valuable information that has the potential to influence clinical practice improvement and health policy for years to come.
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