A new collaborative care approach toward hepatitis C elimination in marginalized populations.

BACKGROUND: Treating marginalized populations with HCV infection for elimination is faced with the challenge for the integration of HCV screening service offered for patients often moving across multiple settings. We envisaged a novel collaborative care approach to identify to what extent HCV patients overlapped between and within these multiple institutions and reported the findings of treatment coverage of these marginalized populations after HCV care cascades. METHODS: We enrolled 7765 patients residing in the Changhua County, Taiwan offered with HCV screening from correctional institutions, HIV clinics, methadone clinics, and the existing HIV surveillance program (four subgroups including police-arrested people, probationers, non-injection drug user, and high-risk behavior people) between 2019 and 2020. The collaborative care and information were integrated through a teamwork of gastroenterologists, psychologists, infectious disease specialists, and nursing coordinators under the auspices of local health authority. RESULTS: The overall participation rate in HCV screening was 92.65% (7194/7765). The prevalence rate was the highest in methadone clinics (90.17%) followed by correctional institutions (37.67%), HIV clinics (34.60%), and the surveillance program (18.14%). We found 25.41% (77/303) of methadone clinic patients, 17.65% (129/731) of HIV clinic patients, and various proportions for 44.09% (41/93) of deferred prosecuted or probationers under surveillance program were also recruited into other settings. Individuals' patient flow within setting was more frequent than that between setting. After calibrating the overlap of patient flow, a total of 1700 anti-HCV positives out of 4074 after screening were traced with available follow-up information to complete 92.52% treatment coverage of 1177 RNA-positives (77.23%) diagnosed from 1524 undergoing RNA testing with similar findings across multiple settings. CONCLUSION: A new collaborative integrated care was adopted for elucidating patient flow between and within multiple settings in order to calibrate the accurate demand for HCV care cascades and enhance HCV treatment coverage in marginalized populations.

Evaluating the effectiveness of population-based breast cancer service screening: an analysis of parsimonious patient survival information with the time-varying Cox model.

BACKGROUND: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial. METHODS: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated. RESULTS: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets. CONCLUSION: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data.

Breast cancers originating from the major lactiferous ducts and the process of neoductgenesis: Ductal Adenocarcinoma of the Breast, DAB.

PURPOSE: To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion. METHOD: All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome. RESULTS: Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article. CONCLUSIONS: Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.

Precision Science on Incidence and Progression of Early-Detected Small Breast Invasive Cancers by Mammographic Features.

The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977-1985 and 1996-2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50-5.26)) and stellate masses (3.76, (95% CI, 3.15-4.53)) but shorter for circular masses (2.65, (95% CI, 2.06-3.55)) in 1996-2010. The similar trends, albeit longer MSTs, were also noted in 1977-1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.

Impact of different types of organ failure on outcome in intensive care unit patients with acute kidney injury.

PURPOSE: The aim of this study was to explore the impact of different types of associated organ failure in patients with acute kidney injury (AKI). MATERIALS AND METHODS: A retrospective analysis of 22 303 adult patients admitted to 22 intensive care units (ICUs) in the United Kingdom and Germany between 1989 and 1999 was done. RESULTS: A total of 7898 patients (35.4%) had AKI. Intensive care unit mortality was 10.7% in patients without AKI, 20.1% in those with AKI I, 25.9% in those with AKI II, and 49.6% in those with AKI III. Intensive care unit mortality rose with increasing number of associated failed organs and preexisting chronic health problems. Respiratory failure was the most common associated organ failure, followed by cardiovascular failure. Less than 2% of the patients had associated neurologic failure alone, but the associated ICU mortality was higher than with single respiratory or cardiovascular failure. In AKI patients with 2 or more failed organ systems, combined cardiovascular and respiratory failure were most common. In multivariate analysis, associated neurologic or hepatic failure had the strongest impact on ICU outcome. There was little change in ICU mortality but a decrease in the standardized mortality ratio over time. CONCLUSIONS: The prognosis of ICU patients with AKI depended on the total number and types of associated failed organ systems. Respiratory failure was the most common associated organ failure, but neurologic and hepatic failures were associated with the worst prognosis.

Black renal transplant recipients have poorer long-term graft survival than CYP3A5 expressers from other ethnic groups.

BACKGROUND: African American transplant recipients have poorer long-term outcomes than Caucasian Americans. This difference was not found in French patients, suggesting socialized medicine overcame this disparity. It has also been hypothesized that the difference relates to the higher prevalence of Black individuals who express the metabolic enzyme cytochrome P4503A5 (CYP3A5), with consequent altered handling of immunosuppressive drugs. METHODS: Records of 555 (50 Black; 505 non-Black) sequential renal transplant recipients from a single UK centre were analysed. RESULTS: Outcomes were significantly worse for Black patients: death-censored graft survival (5-year 66% versus 87%, P = 0.001); halving of year one estimated glomerular filtration rate (mean 8.8 versus 10.8 years, P = 0.008); first-year graft loss (12% versus 3.8%, P = 0.02); and death-censored graft survival in patients surviving the first year with functioning grafts (5-year 77% versus 94%, P = 0.02). Death-censored 5-year graft survival was poorer in Black CYP3A5 expressers than in non-Black CYP3A5 expressers (62% versus 93%, P = 0.002). Following multivariate analysis, the Black group demonstrated poorer graft survival as compared to the non-Black group (hazard ratio 0.46, 95% CI 0.25-0.85, P = 0.002). In a subgroup of genotyped transplant recipients, ethnicity (hazard ratio 0.31, 95% CI 0.15-0.64, P = 0.002), and not CYP3A5 expresser status, persists as an independent risk factor for graft survival following multivariate analysis. CONCLUSION: In this cohort of patients with socialized medicine, Black recipients had poorer long-term outcomes than individuals from other ethnic groups. This was independent of CYP3A5 expresser status.

Correlation between parameters at initiation of renal replacement therapy and outcome in patients with acute kidney injury.

INTRODUCTION: Renal replacement therapy (RRT) is a fully established treatment for critically ill patients with acute kidney injury (AKI) but there are no scientifically established criteria when to initiate it. Our objectives were to describe the epidemiology of critically ill patients with AKI receiving RRT and to evaluate the relationship between biochemical, physiological and comorbid factors at time of RRT and ICU mortality. METHODS: Retrospective analysis of demographic and physiologic data of 1,847 patients who received RRT for AKI in 22 ICUs in UK and Germany between 1989 - 1999. RESULTS: 54.1% of RRT patients died in ICU. ICU survivors were younger, had a lower APACHE II score and fewer failed organ systems on admission to ICU compared to non-survivors. Multivariate analysis showed that at time of initiation of RRT, independent risk factors for ICU mortality were mechanical ventilation [odds ratio (OR) 6.03], neurological failure (OR 2.48), liver failure (OR 2.44), gastrointestinal failure (OR 2.04), pre-existing chronic illnesses (OR 1.74), haematological failure (OR 1.74), respiratory failure (OR 1.62), oligoanuria (OR 1.6), age (OR 1.03), serum urea (OR 1.004) and cardiovascular failure (OR 1.3). A higher pH at initiation of RRT was independently associated with a better outcome. Failure to correct acidosis and development of more organ failure within 48 hours after initiation of RRT were also associated with an increased risk of dying in ICU. CONCLUSIONS: Oligoanuria, acidosis and concomitant dysfunction of other organs at time of RRT were associated with poor survival. In contrast, serum creatinine and urea levels only had a weak correlation with outcome after RRT.

Correlation between the AKI classification and outcome.

INTRODUCTION: The Acute Kidney Injury Network proposed a new classification for acute kidney injury (AKI) distinguishing between three stages. We applied the criteria to a large intensive care unit (ICU) population and evaluated the impact of AKI in the context of other risk factors. METHODS: Using the Riyadh Intensive Care Program database, we applied the AKI classification to 22,303 adult patients admitted to 22 ICUs in the UK and Germany between 1989 and 1999, who stayed in the ICU for 24 hours or longer and did not have end-stage dialysis dependent renal failure. RESULTS: Of the patients, 7898 (35.4%) fulfilled the criteria for AKI (19.1% had AKI I 3.8% had AKI II and 12.5% had AKI III). Mortality in the ICU was 10.7% in patients with no AKI, 20.1% in AKI I, 25.9% in AKI II and 49.6% in AKI III. Multivariate analysis confirmed that AKI III, but not AKI I and AKI II, were independently associated with ICU mortality (odds ratio (OR) = 2.27). Other independent risk factors for ICU mortality were age (OR = 1.03), sequential organ failure assessment (SOFA) score on admission to the ICU (OR = 1.11), pre-existing end-stage chronic health (OR = 1.65), emergency surgery (OR = 2.33), mechanical ventilation (OR = 2.83), maximum number of failed organ systems (OR = 2.80) and non-surgical admission (OR = 3.57). Cardiac surgery, AKI I and renal replacement therapy were associated with a reduced risk of dying in the ICU. AKI II was not an independent risk factor for ICU mortality. Without renal replacement therapy as a criterion, 21% of patients classified as AKI III would have been classified as AKI II or AKI I. Renal replacement therapy as a criterion for AKI III may inadvertently diminish the predictive power of the classification. CONCLUSIONS: The proposed AKI classification correlated with ICU outcome but only AKI III was an independent risk factor for ICU mortality. The use of renal replacement therapy as a criterion for AKI III may have a confounding effect on the predictive power of the classification system as a whole.

Acute kidney injury in the intensive care unit according to RIFLE.

OBJECTIVES: To apply the RIFLE criteria "risk," "injury," and "failure" for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. DESIGN: Retrospective analysis of the Riyadh Intensive Care Program database. SETTING: Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. PATIENTS: Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: : Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. CONCLUSIONS: The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.

Echocardiography-based score to predict outcome after renal transplantation.

BACKGROUND: Given the high cardiac mortality of renal transplant recipients, identification of high-risk patients is important to offer appropriate treatment before transplantation. AIM: To determine patients with high mortality after renal transplantation despite selection according to current criteria. METHODS: Preoperative parameters were collected from 203 renal transplant recipients over a follow-up time of 3.6 (1.9) years. The primary end point was all-cause mortality. RESULTS: 22 deaths (11%) and 12 cardiac failures (6%) were observed. Non-survivors were older (p< or =0.001), had larger left ventricular end-systolic diameter (LVSD) (p< or =0.001) and end-diastolic diameter (p = 0.002), and lower ejection fraction (p< or =0.001). Left ventricular mass index (p = 0.001), maximal wall thickness (p = 0.006) and the proportion with mitral annular calcification (p = 0.001) were significantly higher in the non-survivors. The risk factors for ischaemic heart disease and exercise test data were not significantly different between the two groups. Four independent predictors of mortality after renal transplantation were identified: age > or =50 years (p = 0.002), LVESD > or =3.5 cm (p = 0.002), maximal wall thickness > or =1.4 cm (p = 0.014) and mitral annular calcification (p = 0.036). The 5-year survival estimates for 0, 1, 2 and 3 prognostic factors were 96%, 86%, 69% and 38%, respectively. No patient had four prognostic factors. In patients > or =50 years, the 5-year survival estimates for 0, 1 and 2 additional prognostic factors were 73%, 45% and 18%, respectively. CONCLUSION: In addition to selection according to current guidelines, age and three conventional echocardiography parameters may further improve risk stratification before renal transplantation.

Retroperitoneoscopic live donor nephrectomy in a patient with a double inferior vena cava.

BACKGROUND: Vascular anomalies are considered a contraindication for laparoscopic live donor nephrectomy. We report a successful hand-assisted retroperitoneoscopic live donor nephrectomy from a donor with a double inferior vena cava. MATERIALS AND METHODS: A 37-year-old woman wanted to donate a kidney to her 44-year-old boyfriend who had hypertensive nephropathy. Preoperative donor imaging showed a double inferior vena cava. Each renal vein drains into the ipsilateral inferior vena cava division, making the left renal vein short. A single renal artery, vein, and ureter were noted on both sides. A hand-assisted retroperitoneoscopic left nephrectomy was performed. Blood loss was minimal and the warm ischemia time was 2 minutes. Renal transplantation was performed with good initial perfusion and urine output. Cold ischemia and rewarming time was 25 minutes. RESULTS: The donor postoperative period was uneventful with infrequent need for pain relief. The donor was discharged in good condition 3 days postoperatively. The donor's kidney functions were within the normal range at follow-up 4 months postoperatively. The recipient was discharged in good condition 7 days postoperatively. The recipient is alive with good graft function and unremarkable complications at 4 month follow-up. CONCLUSION: Although vascular anomalies present a surgical challenge, we have shown the feasibility of performing hand-assisted retroperitoneoscopic live donor nephrectomy in a donor with a double vena cava and short renal vein. With comprehensive preoperative assessment, laparoscopic live donor nephrectomy can be done safely in donors with anatomical anomalies. This may increase the number of living donor kidney transplants as it offers lower postoperative morbidity and economic disincentives for potential donors.

The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients.

BACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection, modifies vasculopathy, and shows anti-viral activity. We report first efficacy and safety data of FK778 in human kidney transplant recipients at two concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients were randomized to a 12-week treatment with FK778 in combination with tacrolimus (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received 2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200 microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L, targeted plasma trough levels were reached by Day 3; in half of the patients in group H, the targeted levels were reached by Day 9. Graft survival at week 16 was 89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1% for groups H, L, and P. For the subgroup of patients in which target levels were reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia, the most frequently reported adverse event especially in group H, was reversible. Mean total cholesterol and LDL-cholesterol levels were reduced during FK778 treatment compared with group P. CONCLUSION: FK778 is pharmacologically active, well-tolerated, and safe. To fully benefit from this promising new drug, FK778 dosing will be optimized in subsequent studies.

Panning for gold: screening for potential live kidney donors.

BACKGROUND: Living donation is one method of addressing the gulf between supply and demand for kidney transplants. However, few manage to complete the extensive work up procedure. This study reviews the reasons for failure to complete the live donor renal assessment and suggests options, which may improve the situation. METHODS: Retrospective analysis of data collected over 5 years between 1997 and 2001 of all potential live donors entering the assessment programme. RESULTS: 189 (103 female, 86 male) potential donors entered the assessment process. Thirty-four (18%) actually donated comprising 17 (50%) siblings, nine (26%) parents and eight (24%) unrelated donors. Of the 155 who did not donate, 46 (30%) had blood group or immunological incompatibility and 42 (27%) withdrew. Twenty-three (15%) were medically unfit, mostly due to cardiovascular disease and 16 (10%) had insufficient renal function for safe donation. CONCLUSION: Live donor transplantation offers an attractive source of high quality organs, but considerable time and effort is required to realize this. Manipulation of immunological incompatibility, psychological assessment and counselling of those likely to withdraw may significantly enhance the yield. Support should also be provided for those unable to donate for whatever reason.