The Cost of Patients with Chronic Kidney Failure Before Dialysis: Results from the IRIDE Observational Study

Background Chronic kidney disease (CKD) is an important public health problem. Most of the evidence on its costs relates to patients receiving dialysis or kidney transplants, which shows that, in these phases, CKD poses a high burden to payers. Less evidence is available on the costs of the predialytic phase. Objective The aim of this study was to estimate the annual cost of patients with CKD not receiving dialysis treatment, using the Italian healthcare system perspective and a prospective approach. Methods A 3-year observational study (December 2010\u2013 September 2014) was carried out to collect data on resource consumption for 864 patients with CKD. Costs were estimated for both patients who completed the followup and dropouts. Results The mean annual total (healthcare) cost per patient equalled \u20ac2723 (95% confidence interval 2463.0\u20132983.3). Disease severity (higher CKD stage), multiple comorbidities, dropout status and belonging to the southern region are predictive of higher costs. Pharmaceuticals, hospitalisation, and outpatient services account for 71.5, 18.8 and 9.7% of total healthcare expenditure, respectively. Recent estimates of Italian costs of patients receiving dialysis are nine times the unit costs of CKD for patients estimated in this study. Unit costs at stage 5 CKD (the highest level of severity) equals 4.7 times the costs for patients at stage 1 CKD. Conclusion Despite its limitations, this study provides further evidence on the opportunity to invest in the first phases of CKD to avoid progression and an increase in healthcare costs

Cancers of unknown primary origin: current perspectives and future therapeutic strategies

It is widely accepted that systemic neoplastic spread is a late event in tumour progression. However, sometimes, rapidly invasive cancers are diagnosed because of appearance of metastatic lesions in absence of a clearly detectable primary mass. This kind of disease is referred to as cancer of unknown primary (CUP) origin and accounts for 3-5% of all cancer diagnosis. There is poor consensus on the extent of diagnostic and pathologic evaluations required for these enigmatic cases which still lack effective treatment. Although technology to predict the primary tumour site of origin is improving rapidly, the key issue is concerning the biology which drives early occult metastatic spreading. This review provides the state of the art about clinical and therapeutic management of this malignant syndrome; main interest is addressed to the most recent improvements in CUP molecular biology and pathology, which will lead to successful tailored therapeutic options

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD

The Cost of Patients with Chronic Kidney Failure Before Dialysis: Results from the IRIDE Observational Study

Chronic kidney disease (CKD) is an important public health problem. Most of the evidence on its costs relates to patients receiving dialysis or kidney transplants, which shows that, in these phases, CKD poses a high burden to payers. Less evidence is available on the costs of the predialytic phase

ATL

OBJECTIVE: The p16 (p16(Ink4a)) tumor-suppressor protein is a biomarker for activated expression of human papillomavirus oncogenes. However, data are insufficient to determine whether p16 overexpression predicts the risk for progression of low-grade cervical intraepithelial neoplasia (CIN). This study was aimed at evaluating the risk for progression to CIN2 or worse during a 3-year follow-up of an unselected series of 739 patients with CIN1 biopsy specimens tested for p16 expression. METHODS: Positivity of p16 was defined as a diffuse overexpression in the basal/parabasal cell layers. Selection biases were ruled out using a control group of 523 patients with CIN1 biopsies not tested for p16 expression. Analysis was based on the ratio of progression rates. RESULTS: In the first year of follow-up, the 216 patients (29%) with p16-positive CIN1 had a higher progression rate (12.3%) than did the 523 patients with p16-negative CIN1 (2.2%) (rate ratio, 5.5; 95% confidence interval [CI], 2.59-11.71). In the second and third years, differences were smaller (rate ratio, 1.32 and 1.14, respectively) and not significant. The patients with p16-positive CIN1 also had a lower risk for regression to normal in the first year of follow-up (rate ratio, 0.55; 95% confidence interval, 0.42-0.71) and nonsignificant changes in the second and third years (rate ratio, 0.81 and 0.84, respectively). CONCLUSIONS: The patients with p16-positive CIN1 had an increased risk for progression that was concentrated in the first year of follow-up. Immunostaining of p16 could have a role in short-term surveillance of patients with CIN1. Further research should focus on midterm/long-term outcomes of p16-positive CIN1.

The Integration of qSOFA with Clinical Variables and Serum Biomarkers Improves the Prognostic Value of qSOFA Alone in Patients with Suspected or Confirmed Sepsis at ED Admission.

Abstract Background: The prognostic value of quick sepsis-related organ failure assessment (qSOFA) outside intensive care units has been criticized. Therefore, we aimed to improve its ability in predicting 30-day all-cause mortality, and in ruling out the cases at high risk of death among patients with suspected or confirmed sepsis at emergency department (ED) admission. Methods: This study is a secondary analysis of a prospective multicenter study. We built three predictive models combining qSOFA with the clinical variables and serum biomarkers that resulted in an independent association with 30-day mortality, in both 848 undifferentiated patients (Group 1) and in 545 patients definitively diagnosed with sepsis (Group 2). The models reaching the highest negative predictive value (NPV) with the minimum expenditure of biomarkers in Group 1 and in Group 2 were validated in two cohorts of patients initially held out due to missing data. Results: In terms of the area under the receiver-operating characteristic curve, all six models significantly exceeded qSOFA in predicting prognosis. An "extended" qSOFA (eqSOFA1) in Group 1 and an eqSOFA2 integrated with C-reactive protein and mid-regional proadrenomedullin (eqSOFA2+CRP+MR-proADM) in Group 2 reached the best NPV (0.94 and 0.93, respectively) and ease of use. eqSOFA1 and eqSOFA2+CRP+MR-proADM performed equally well in both the inception and validation cohorts. Conclusions: We have derived and validated two prognostic models that outweigh qSOFA in predicting mortality and in identifying the low risk of death among patients with suspected or confirmed sepsis at ED admission

Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

365noBackground and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.nonenoneNordio M.; Reboldi G.; Di Napoli A.; Quintaliani G.; Alberici F.; Postorino M.; Aucella F.; Messa P.; Brunori G.; Brunori G.; Bosco M.; Malberti F.; Mandreoli M.; Mazzaferro S.; Movilli E.; Ravera M.; Salomone M.; Santoro D.; PostorinoLimido M.A.; Bonomini M.; Stingone A.; Maccarone M.; Di Loreto E.; Stacchiotti L.; Malandra R.; Chiarella S.; D'Agostino F.; Fuiano G.; Nicodemo L.; Bonofiglio R.; Greco S.; Mallamaci F.; Barreca E.; Caserta C.; Bruzzese V.; Galati D.; Tramontana D.; Viscione M.; Chiuchiolo L.; Tuccillo S.; Sepe M.; Vitale F.; Ciriana E.; Santoro D.; Martignetti V.; Caserta D.; Stizzo A.; Romano A.; Iulianiello G.; Cascone E.; Minicone P.; Chiricone D.; Delgado G.; Barbato A.; Celentano S.; Molfino I.; Coppola S.; Raiola I.; Abategiovanni M.; Borrelli S.; Margherita C.; Bruno F.; Ida M.; Aliperti E.; Potito D.; Cuomo G.; De Luca M.; Merola M.; Botta C.; Garofalo G.; Alinei P.; Paglionico C.; Roano M.; Vitale S.; Ierardi R.; Fimiani V.; Conte G.; Di Natale G.; Romano M.; Di Marino V.; Scafarto A.; Meccariello S.; Pecoraro C.; Di Stazio E.; Di Meglio E.; Cuomo A.; Maresca B.; Rotaia E.; Capasso G.; Auricchio M.; Pluvio C.; Maddalena L.; De Maio A.; Palladino G.; Buono F.; Gigliotti G.; Mandreoli M.; Mancini E.; La Manna G.; Storari A.; Mosconi G.; Cappelli G.; Scarpioni R.; Gregorini M.; Rigotti A.; Mancini W.; Bianco F.; Boscutti G.; Amici G.; Tosto M.; Fini R.; Pace G.; Cioffi A.; Boccia E.; Di Lullo L.; Di Zazzo G.; Simonelli R.; Bondatti F.; Miglio L.; Rifici N.; Treglia A.; Muci M.; Baldinelli G.; Rizzi E.; Lonzi M.; De Cicco C.; Forte F.; De Paolis P.; Grandaliano G.; Cuzziol C.; Torre V.M.; Sfregola P.; Rossi V.; Fabio G.; Flammini A.; Filippini A.; Onorato L.; Vendola F.; Di Daniela N.; Alfarone C.; Scabbia L.; Ferrazzano M.; Grotta B.D.; Gamberini M.; Fazzari L.; Mene P.; Morgia A.; Catucci A.; Palumbo R.; Puliti M.; Marinelli R.; Polito P.; Marrocco F.; Morabito S.; Rocca R.; Nazzaro L.; Lavini R.; Iamundo V.; Chiappini M.; Casarci M.; Morosetti M.; Hassan S.; Alfarone C.; Ferrazzano M.; Firmi G.; Galliani M.; Serraiocco M.; Feriozzi S.; Valentini W.; Sacco P.; Garibotto G.; Cappelli V.; Saffioti C.; Repetto M.; Rolla D.; Lorenz M.; Pedrini L.; Polonioli D.; Galli E.; Ruggenenti P.; Scolari F.; Bove S.; Costantino E.; Bracchi M.; Mangano S.; Depetri G.; Malberti F.; La Milia V.; Farina M.; Zecchini S.; Savino R.; Melandri M.; Guastoni C.; Paparella M.; Gallieni M.; Minetti E.; Bisegna S.; Messa P.; Righetti M.; Badalamenti S.; Guastoni C.; Alberghini E.; Bertoli S.; Fabbrini P.; Albrizio P.; Rampino T.; Colturi C.; Rombola G.; Lucatello A.; Guerrini E.; Ranghino A.; Lenci F.; Fanciulli E.; Santarelli S.; Damiani C.; Garofalo D.; Sopranzi F.; Santoferrara A.; Di Luca M.; Galiotta P.; Brigante M.; Manganaro M.; Maffei S.; Berto I.; Besso L.; Viglino G.; Besso L.; Cusinato S.; ChiarinottiChiappero D.F.; Tognarelli G.; Gianoglio B.; Salomone M.; Forneris G.; Biancone L.; Savoldi S.; Vitale C.; Boero R.; Filiberti O.; Borzumati M.; Gesualdo L.; Lomonte C.; Gernone G.; Pallotta G.; Di Paolo S.; Vernaglione L.; Specchio A.; Stallone G.; Dell'Aquila R.; Aucella F.; Sandri G.; Russo F.; Napoli M.; Marangi A.; Morrone L.; Di Stratis C.; Fresu A.; Cicu F.; Murtas S.; Manca O.; Pani A.; Pilloni M.; Pistis R.; Cadoni M.; Contu B.; Logias F.; Ivaldi R.; Fancello S.; Cossu M.; Lepori G.; Lepori G.; Vittoria S.; Battiati E.; Arnone M.; Rome M.; Barbera A.; Granata A.; Collura G.; Dico C.L.; Pugliese G.; Di Natale E.; Rizzari G.; Cottone L.; Longo N.; Battaglia G.; Marcantoni C.; Giannetto G.; Tumino G.; Randazzo F.; Bellissimo L.; Faro F.L.; Grippaldi F.; Urso S.; Quattrone G.; Todaro I.; Vincenzo D.; Murgo A.; Masuzzo M.; Pisacane A.; Monardo P.; Santoro D.; Pontorierro M.; Quari C.; Bauro A.; Chimenz R.R.; Alfio D.; Girasole F.; Cascio A.L.; Caviglia A.; Tornese F.; Sirna F.; Altieri C.; Cusumano R.; Saveriano V.; La Corte A.; Locascio G.; Rotolo U.; Rome M.; Musso S.; Risuglia L.; Blanco G.; Minardo G.; Castellino S.; Zappulla Z.; Randone S.; Di Francesca M.; Cassetti C.C.; Oddo G.; Buscaino G.; Mucaria F.; Barraco V.I.; Di Martino A.; Mucaria F.; Rallo D.; Dani L.; Campolo G.; Manescalchi F.; Biagini M.; Agate M.; Panichi V.; Casani A.; Traversari L.; Garosi G.; Brunori G.; Tabbi M.; Selvi A.; Cencioni L.; Fagugli R.; Timio F.; Leveque A.; Manes M.; Mennella G.; Calo L.; Fiorini F.; Abaterusso C.; Calzavara P.; Nordio M.; Meneghel G.; Bonesso C.; Gambaro G.; Gammaro L.; Rugiu C.; Dell'Aquila R.; Dell'Aquila R.; Ronco C.; Rugiu C.Nordio, M.; Reboldi, G.; Di Napoli, A.; Quintaliani, G.; Alberici, F.; Postorino, M.; Aucella, F.; Messa, P.; Brunori, G.; Brunori, G.; Bosco, M.; Malberti, F.; Mandreoli, M.; Mazzaferro, S.; Movilli, E.; Ravera, M.; Salomone, M.; Santoro, D.; Postorinolimido, M. A.; Bonomini, M.; Stingone, A.; Maccarone, M.; Di Loreto, E.; Stacchiotti, L.; Malandra, R.; Chiarella, S.; D'Agostino, F.; Fuiano, G.; Nicodemo, L.; Bonofiglio, R.; Greco, S.; Mallamaci, F.; Barreca, E.; Caserta, C.; Bruzzese, V.; Galati, D.; Tramontana, D.; Viscione, M.; Chiuchiolo, L.; Tuccillo, S.; Sepe, M.; Vitale, F.; Ciriana, E.; Santoro, D.; Martignetti, V.; Caserta, D.; Stizzo, A.; Romano, A.; Iulianiello, G.; Cascone, E.; Minicone, P.; Chiricone, D.; Delgado, G.; Barbato, A.; Celentano, S.; Molfino, I.; Coppola, S.; Raiola, I.; Abategiovanni, M.; Borrelli, S.; Margherita, C.; Bruno, F.; Ida, M.; Aliperti, E.; Potito, D.; Cuomo, G.; De Luca, M.; Merola, M.; Botta, C.; Garofalo, G.; Alinei, P.; Paglionico, C.; Roano, M.; Vitale, S.; Ierardi, R.; Fimiani, V.; Conte, G.; Di Natale, G.; Romano, M.; Di Marino, V.; Scafarto, A.; Meccariello, S.; Pecoraro, C.; Di Stazio, E.; Di Meglio, E.; Cuomo, A.; Maresca, B.; Rotaia, E.; Capasso, G.; Auricchio, M.; Pluvio, C.; Maddalena, L.; De Maio, A.; Palladino, G.; Buono, F.; Gigliotti, G.; Mandreoli, M.; Mancini, E.; La Manna, G.; Storari, A.; Mosconi, G.; Cappelli, G.; Scarpioni, R.; Gregorini, M.; Rigotti, A.; Mancini, W.; Bianco, F.; Boscutti, G.; Amici, G.; Tosto, M.; Fini, R.; Pace, G.; Cioffi, A.; Boccia, E.; Di Lullo, L.; Di Zazzo, G.; Simonelli, R.; Bondatti, F.; Miglio, L.; Rifici, N.; Treglia, A.; Muci, M.; Baldinelli, G.; Rizzi, E.; Lonzi, M.; De Cicco, C.; Forte, F.; De Paolis, P.; Grandaliano, G.; Cuzziol, C.; Torre, V. M.; Sfregola, P.; Rossi, V.; Fabio, G.; Flammini, A.; Filippini, A.; Onorato, L.; Vendola, F.; Di Daniela, N.; Alfarone, C.; Scabbia, L.; Ferrazzano, M.; Grotta, B. D.; Gamberini, M.; Fazzari, L.; Mene, P.; Morgia, A.; Catucci, A.; Palumbo, R.; Puliti, M.; Marinelli, R.; Polito, P.; Marrocco, F.; Morabito, S.; Rocca, R.; Nazzaro, L.; Lavini, R.; Iamundo, V.; Chiappini, M.; Casarci, M.; Morosetti, M.; Hassan, S.; Alfarone, C.; Ferrazzano, M.; Firmi, G.; Galliani, M.; Serraiocco, M.; Feriozzi, S.; Valentini, W.; Sacco, P.; Garibotto, G.; Cappelli, V.; Saffioti, C.; Repetto, M.; Rolla, D.; Lorenz, M.; Pedrini, L.; Polonioli, D.; Galli, E.; Ruggenenti, P.; Scolari, F.; Bove, S.; Costantino, E.; Bracchi, M.; Mangano, S.; Depetri, G.; Malberti, F.; La Milia, V.; Farina, M.; Zecchini, S.; Savino, R.; Melandri, M.; Guastoni, C.; Paparella, M.; Gallieni, M.; Minetti, E.; Bisegna, S.; Messa, P.; Righetti, M.; Badalamenti, S.; Guastoni, C.; Alberghini, E.; Bertoli, S.; Fabbrini, P.; Albrizio, P.; Rampino, T.; Colturi, C.; Rombola, G.; Lucatello, A.; Guerrini, E.; Ranghino, A.; Lenci, F.; Fanciulli, E.; Santarelli, S.; Damiani, C.; Garofalo, D.; Sopranzi, F.; Santoferrara, A.; Di Luca, M.; Galiotta, P.; Brigante, M.; Manganaro, M.; Maffei, S.; Berto, I.; Besso, L.; Viglino, G.; Besso, L.; Cusinato, S.; Chiarinottichiappero, D. F.; Tognarelli, G.; Gianoglio, B.; Salomone, M.; Forneris, G.; Biancone, L.; Savoldi, S.; Vitale, C.; Boero, R.; Filiberti, O.; Borzumati, M.; Gesualdo, L.; Lomonte, C.; Gernone, G.; Pallotta, G.; Di Paolo, S.; Vernaglione, L.; Specchio, A.; Stallone, G.; Dell'Aquila, R.; Aucella, F.; Sandri, G.; Russo, F.; Napoli, M.; Marangi, A.; Morrone, L.; Di Stratis, C.; Fresu, A.; Cicu, F.; Murtas, S.; Manca, O.; Pani, A.; Pilloni, M.; Pistis, R.; Cadoni, M.; Contu, B.; Logias, F.; Ivaldi, R.; Fancello, S.; Cossu, M.; Lepori, G.; Lepori, G.; Vittoria, S.; Battiati, E.; Arnone, M.; Rome, M.; Barbera, A.; Granata, A.; Collura, G.; Dico, C. L.; Pugliese, G.; Di Natale, E.; Rizzari, G.; Cottone, L.; Longo, N.; Battaglia, G.; Marcantoni, C.; Giannetto, G.; Tumino, G.; Randazzo, F.; Bellissimo, L.; Faro, F. L.; Grippaldi, F.; Urso, S.; Quattrone, G.; Todaro, I.; Vincenzo, D.; Murgo, A.; Masuzzo, M.; Pisacane, A.; Monardo, P.; Santoro, D.; Pontorierro, M.; Quari, C.; Bauro, A.; Chimenz, R. R.; Alfio, D.; Girasole, F.; Cascio, A. L.; Caviglia, A.; Tornese, F.; Sirna, F.; Altieri, C.; Cusumano, R.; Saveriano, V.; La Corte, A.; Locascio, G.; Rotolo, U.; Rome, M.; Musso, S.; Risuglia, L.; Blanco, G.; Minardo, G.; Castellino, S.; Zappulla, Z.; Randone, S.; Di Francesca, M.; Cassetti, C. C.; Oddo, G.; Buscaino, G.; Mucaria, F.; Barraco, V. I.; Di Martino, A.; Mucaria, F.; Rallo, D.; Dani, L.; Campolo, G.; Manescalchi, F.; Biagini, M.; Agate, M.; Panichi, V.; Casani, A.; Traversari, L.; Garosi, G.; Brunori, G.; Tabbi, M.; Selvi, A.; Cencioni, L.; Fagugli, R.; Timio, F.; Leveque, A.; Manes, M.; Mennella, G.; Calo, L.; Fiorini, F.; Abaterusso, C.; Calzavara, P.; Nordio, M.; Meneghel, G.; Bonesso, C.; Gambaro, G.; Gammaro, L.; Rugiu, C.; Dell'Aquila, R.; Dell'Aquila, R.; Ronco, C.; Rugiu, C