HPV-FASTER: Combined strategies of HPV vaccination and HPV screening towards a one visit for cervical cancer preventive campaigns

HPV screening and vaccination are complementary preventive options often implemented as separate and non-coordinated public health programs. The HPVFASTER protocols aim to address this disconnect by combining both strategies with the ultimate purpose of accelerating the reduction of cervical cancer incidence and mortality and making the programs both costeffective and sustainable. Results from two phase III trials comparing HPV vaccination against placebo among adult women (aged up to 45 years and 55 years for 4vHPV and 2vHPV vaccines, respectively)1,2 showing high protection against HPV type specific infections and persistent infections and the excellent and consistent results of the HPVscreening trials3-5 provide the basis for the HPV-FASTER proposal. The recognition of indications to vaccinate adult women in Europe6-8 and the US9 which do not include an upper age limit, favor the exploration of combined protocols of screening and vaccination and broadening the vaccine indications in developed and developing countries

HPV vaccination: Are we overlooking additional opportunities to control HPV infection and transmission?

Human papillomavirus virus-like particles (HPV VLPs) have distinctive immunogenic properties that generate a durable antibody response, producing high-quality neutralizing antibodies. By vaccination, i.e., intramuscular injection of these HPV VLPs, the viral survival strategy of avoiding exposure to the systemic immune system is completely overruled, and large amounts of vaccine-induced systemic antibodies are generated. These systemic circulating antibodies are easily transuded to the genital mucosa and are detectable in female genital secretions. It is well accepted that these antibodies interact with the virions presented by an infected partner and inhibit infection. However, much less attention has been paid to the role of anti-HPV vaccine-induced antibodies in an HPV-infected individual where infectious virions are encountered by neutralizing antibodies in mucosal secretions. There is a clear need to further investigate and document this role. Indeed, if HPV vaccination of HPV-infected women has an effect on HPV transmission, auto-inoculation, and relapse after treatment, this may influence how we model, assess, and implement HPV vaccination programmes. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

What is the relevance of an ambulatory quick diagnosis unit or inpatient admission for the diagnosis of pancreatic cancer? A retrospective study of 1004 patients

Quick diagnosis units (QDU) have become an alternative hospital-based ambulatory medicine strategy to inpatient hospitalization for potentially serious illnesses in Spain. Whether diagnosis of pancreatic cancer is better accomplished by an ambulatory or inpatient approach is unknown. The main objective of this retrospective study was to examine and compare the diagnostic effectiveness of a QDU or inpatient setting in patients with pancreatic cancer. Patients with a diagnosis of pancreatic adenocarcinoma who had been referred to a university, tertiary hospital-based QDU or hospitalized between 2005 and 2018 were eligible. Presenting symptoms and signs, risk and prognostic factors, and time to diagnosis were compared. The costs incurred during the diagnostic assessment were analyzed with a microcosting method. A total of 1004 patients (508 QDU patients and 496 inpatients) were eligible. Admitted patients were more likely than QDU patients to have weight loss, asthenia, anorexia, abdominal pain, jaundice, and palpable hepatomegaly. Time to diagnosis of inpatients was similar to that of QDU patients (4.1 [0.8 vs 4.3 [0.6] days; P = .163). Inpatients were more likely than QDU patients to have a tumor on the head of the pancreas, a tumor size >2 cm, a more advanced nodal stage, and a poorer histological differentiation. No differences were observed in the proportion of metastatic and locally advanced disease and surgical resections. Microcosting revealed a cost of 347.76 (48.69) per QDU patient and 634.36 (80.56) per inpatient (P < .001). Diagnosis of pancreatic cancer is similarly achieved by an inpatient or QDU clinical approach, but the latter seems to be cost-effective. Because the high costs of hospitalization, an ambulatory diagnostic assessment may be preferable in these patients

Trends in Hospitalization of Patients with Potentially Serious Diseases Evaluated at a Quick Diagnosis Clinic

Although quick diagnosis units (QDU) have become a cost-effective alternative to inpatient admission for diagnosis of potentially serious diseases, the rate of return hospitalizations among evaluated patients is unknown. This study examined the temporal trends in admissions of QDU patients through 15 years. Adult patients referred to QDU from 2004 to 2019 who were hospitalized between the first and last visit in the unit were eligible. Decisions about admissions were mainly based on the Appropriateness Evaluation Protocol and required independent validation by experienced clinicians using a customized tool. The final analysis included 825 patients. Patient characteristics and major reasons for admission were compared each year and linear trends were analyzed. Admission rates decreased from 7.2% in 2004-2005 to 4.3% in 2018-2019 (p < 0.0001). While a significant increasing trend was observed in the rate of admissions due to cancer-related complications (from 39.5% in 2004-2005 to 61.7% in 2018-2019; p < 0.0001), those due to anemia-related complications and scheduled invasive procedures experienced a significant downward trend. A likely explanation for these declining trends was the relocation of the unit to a new daycare center in 2013-2014 with recovery rooms and armchairs for IV treatments. The facts of this study could help in the provision of anticipatory guidance for the optimal management of patients at risk of clinical complications

Sarcoidosis or primary Sjögren's syndrome?

Correspondence: SIR, We were interested to read the case report by Melsom and coworkers.' We have been followinl up a patient who presented a similar difficult diagnosis

Unintentional weight loss: Clinical characteristics and outcomes in a prospective cohort of 2677 patients.

Background Whereas there are numerous studies on unintentional weight loss (UWL), these have been limited by small sample sizes, short or variable follow‐up, and focus on older patients. Although some case series have revealed that malignancies escaping early detection and uncovered subsequently are exceptional, reported follow-ups have been too short or unspecified and necropsies seldom made. Our objective was to examine the etiologies, characteristics, and long-term outcome of UWL in a large cohort of outpatients. Methods We prospectively enrolled patients referred to an outpatient diagnosis unit for evaluation of UWL as a dominant or isolated feature of disease. Eligible patients underwent a standard baseline evaluation with laboratory tests and chest X-ray. Patients without identifiable causes 6 months after presentation underwent a systematic follow-up lasting for 60 further months. Subjects aged ≥65 years without initially recognizable causes underwent an oral cavity examination, a videofluoroscopy or swallowing study, and a depression and cognitive assessment. Results Overall, 2677 patients (mean age, 64.4 [14.7] years; 51% males) were included. Predominant etiologies were digestive organic disorders (nonmalignant in 17% and malignant in 16%). Psychosocial disorders explained 16% of cases. Oral disorders were second to nonhematologic malignancies as cause of UWL in patients aged ≥65 years. Although 375 (14%) patients were initially diagnosed with unexplained UWL, malignancies were detected in only 19 (5%) within the first 28 months after referral. Diagnosis was established at autopsy in 14 cases. Conclusion This investigation provides new information on the relevance of follow-up in the long-term clinical outcome of patients with unexplained UWL and on the role of age on this entity. Although unexplained UWL seldom constitutes a short-term medical alert, malignancies may be undetectable until death. Therefore, these patients should be followed up regularly (eg yearly visits) for longer than reported periods, and autopsies pursued when facing unsolved deaths

Perception of quality of care of patients with potentially severe diseases evaluated at a distinct quick diagnostic delivery model: a cross-sectional study

Background: Although hospital-based outpatient quick diagnosis units (QDU) are an increasingly recognized cost-effective alternative to hospitalization for the diagnosis of potentially serious diseases, patient perception of their quality of care has not been evaluated well enough. This cross-sectional study analyzed the perceived quality of care of a QDU of a public third-level university hospital in Barcelona. Methods: One hundred sixty-two consecutive patients aged ≥ 18 years attending the QDU over a 9-month period were invited to participate. A validated questionnaire distributed by the QDU attending physician and completed at the end of the first and last QDU visit evaluated perceived quality of care using six subscales. Results: Response rate was 98%. Perceived care in all subscales was high. Waiting times were rated as 'short'/'very short' or 'better'/'much better' than expected by 69-89% of respondents and physical environment as 'better'/'much better' than expected by 94-96 %. As to accessibility, only 3% reported not finding the Unit easily and 7% said that frequent travels to hospital for visits and investigations were uncomfortable. Perception of patient-physician encounter was high, with 90-94% choosing the positive extreme ends of the clinical information and personal interaction subscales items. Mean score of willingness to recommend the Unit using an analogue scale where 0 was 'never' and 10 'without a doubt' was 9.5 (0.70). On multivariate linear regression, age >65 years was an independent predictor of clinical information, personal interaction, and recommendation, while age 18-44 years was associated with lower scores in these subscales. No schooling predicted higher clinical information and recommendation scores, while university education had remarkable negative influence on them. Having ≥4 QDU visits was associated with lower time to diagnosis and recommendation scores and malignancy was a negative predictor of time to diagnosis, clinical information, and recommendation. Discussion: It is worthy of note that the questionnaire evaluated patient perception and opinions of healthcare quality including recommendation rather than simply satisfaction. It has been argued that perception of quality of care is a more valuable approach than satisfaction. In addition to embracing an affective dimension, satisfaction appears more dependent on patient expectations than is perception of quality. Conclusions: While appreciating that completing the questionnaire immediately after the visit and its distribution by the QDU physician may have affected the results, scores of perceived quality of care including recommendation were high. There were, however, significant differences in several subscales associated with age, education, number of QDU visits, and diagnosis of malignant vs. benign condition

Quick outpatient diagnosis in small district or general tertiary hospitals: A comparative observational study.

While quick diagnosis units (QDUs) have expanded as an innovative cost-effective alternative to admission for workup, studies investigating how QDUs compare are lacking. This study aimed to comparatively describe the diagnostic performance of the QDU of an urban district hospital and the QDU of its reference general hospital.This was an observational descriptive study of 336 consecutive outpatients aged ≥18 years referred to the QDU of a urban district hospital in Barcelona (QDU1) during 2009 to 2016 for evaluation of suspected severe conditions whose physical performance allowed them to travel from home to hospital and back for visits and examinations. For comparison purposes, 530 randomly selected outpatients aged ≥18 years referred to the QDU of the reference tertiary hospital (QDU2), also in Barcelona, were included. Clinical and QDU variables were analyzed and compared.Mean age and sex were similar (61.97 (19.93) years and 55% of females in QDU1 vs 60.0 (18.81) years and 52% of females in QDU2; P values = .14 and .10, respectively). Primary care was the main referral source in QDU1 (69%) and the emergency department in QDU2 (59%). Predominant referral reasons in QDU1 and 2 were unintentional weight loss (UWL) (21 and 16%), anemia (14 and 21%), adenopathies and/or palpable masses (10 and 11%), and gastrointestinal symptoms (10 and 19%). Time-to-diagnosis was longer in QDU1 than 2 (12 [1-28] vs 8 [4-14] days; P 2 visits to be diagnosed were in general more likely to be males, to have UWL and adenopathies and/or palpable masses but less likely anemia, to undergo more examinations except endoscopy, and to be referred onward to specialist outpatient clinics.Despite some differences, results showed that, for diagnostic purposes, the overall performance and effectiveness of QDUs of urban district and reference general hospitals in evaluating patients with potentially serious conditions were similar. This study, the first to compare the performance of 2 hospital-based QDUs, adds evidence to the opportunity of producing standardized guidelines to optimize QDUs infrastructure, functioning, and efficiency

Time to diagnosis and associated costs of an outpatient vs inpatient setting in the diagnosis of lymphoma: a retrospective study of a large cohort of major lymphoma subtypes in Spain

Background: Mainly because of the diversity of clinical presentations, diagnostic delays in lymphoma can be excessive. The time spent in primary care before referral to the specialist may be relatively short compared with the interval between hospital appointment and diagnosis. Although studies have examined the diagnostic intervals and referral patterns of patients with lymphoma, the time to diagnosis of outpatient compared to inpatient settings and the costs incurred are unknown. Methods: We performed a retrospective study at two academic hospitals to evaluate the time to diagnosis and associated costs of hospital-based outpatient diagnostic clinics or conventional hospitalization in four representative lymphoma subtypes. The frequency, clinical and prognostic features of each lymphoma subtype and the activities of the two settings were analyzed. The costs incurred during the evaluation were compared by microcosting analysis. Results: A total of 1779 patients diagnosed between 2006 and 2016 with classical Hodgkin, large B-cell, follicular, and mature nodal peripheral T-cell lymphomas were identified. Clinically aggressive subtypes including large B-cell and peripheral T-cell lymphomas were more commonly diagnosed in inpatients than in outpatients (39.1 vs 31.2% and 18.9 vs 13.5%, respectively). For each lymphoma subtype, inpatients were older and more likely than outpatients to have systemic symptoms, worse performance status, more advanced Ann Arbor stages, and high-risk prognostic scores. The admission time for diagnosis (i.e. from admission to excisional biopsy) of inpatients was significantly shorter than the time to diagnosis of outpatients (12.3 [3.3] vs 16.2 [2.7] days; P < .001). Microcosting revealed a mean cost of (sic)4039.56 (513.02) per inpatient and of (sic)1408.48 (197.32) per outpatient, or a difference of (sic)2631.08 per patient. Conclusions: Although diagnosis of lymphoma was quicker with hospitalization, the outpatient approach seems to be cost-effective and not detrimental. Despite the considerable savings with the latter approach, there may be hospitalization-associated factors which may not be properly managed in an outpatient unit (e.g. aggressive lymphomas with severe symptoms) and the cost analysis did not account for this potentially added value. While outcomes were not analyzed in this study, the impact on patient outcome of an outpatient vs inpatient diagnostic setting may represent a challenging future research

Primary care referrals of patients with potentially serious diseases to the emergency department or a quick diagnosis unit: a cross-sectional retrospective study.

BACKGROUND: In Spain, primary healthcare (PHC) referrals for diagnostic procedures are subject to long waiting-times, and physicians and patients often use the emergency department (ED) as a shortcut. We aimed to determine whether patients evaluated at a hospital outpatient quick diagnosis unit (QDU) who were referred to ED from 12 PHC centers could have been directly referred to QDU, thus avoiding ED visits. As a secondary objective, we determined the proportion of QDU patients who might have been evaluated in a less rapid, non-QDU setting. METHODS: We carried out a cross-sectional retrospective cohort study of patients with potentially serious conditions attended by the QDU from December 2007 to December 2012. We established 2 groups of patients: 1) patients referred from PHC to QDU (PHC-QDU group) and 2) patients referred from PHC to ED, then to QDU (PHC-ED-QDU group). Two observers assessed the appropriateness/inappropriateness of each referral using a scoring system. The interobserver agreement was assessed by calculating the kappa index. Multivariate logistic regression analysis was performed to identify the factors associated with the dependent variable 'ED referral'. RESULTS: We evaluated 1186 PHC-QDU and 1004 PHC-ED-QDU patients and estimated that 93.1% of PHC-ED-QDU patients might have been directly referred to QDU. In contrast, 96% of PHC-QDU patients were found to be appropriately referred to QDU first. The agreement for PHC-QDU referrals (PHC-QDU group) was rated as excellent (ϰ=0.81), while it was rated as good for PHC-ED referrals (PHC-ED-QDU group) (ϰ=0.75). The mean waiting-time for the first QDU visit was longer in PHC-QDU (4.8 days) than in PHC-ED-QDU (2.6 days) patients (P=.001). On multivariate analysis, anemia (OR 2.87, 95% CI 1.49-4.55, P<.001), rectorrhagia (OR 2.18, 95% CI 1.10-3.77, P=.01) and febrile syndrome (OR 2.53, 95% CI 1.33-4.12, P=.002) were independent factors associated with ED referral. Nearly one-fifth of all QDU patients were found who might have been evaluated in a less rapid, non-QDU setting. CONCLUSIONS: Most PHC-ED-QDU patients might have been directly referred to QDU from PHC, avoiding the inconvenience of the ED visit. A stricter definition of QDU evaluation criteria may be needed to improve and hasten PHC referrals