Purpose of the studyConsidering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV‐related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs.MethodsHIV patients were consecutively enrolled in 2010‐2011. We considered socio‐demographic characteristics, HIV history, cardiovascular risk factors, low energy fractures, bone density. Psychological factors were assessed by BDI, DS14 and TAS‐20. The MFRS was calculated as the sum of the following: age (<30y 1 point; 1 point increase every 5y, 10 for≥70); AIDS diagnosis (5); CD4 nadir (5 if <100; 1 point less every 100 CD4 increase); ART line (0 first, up to 5 for≥6 lines); lipodistrophy (5); HCV coinfection (7); education (1 degree, 2 secondary, 3 primary); alcohol (3) and drug abuse (5); working activity (3 if unemployed); hypertension (3); cholesterol≥200 mg/dl (3); diabetes (3); Framingham score (7 if>7%); creatinine (0 if <1 mg/dl, 1 if<1.2; 2 if<1.5>1.2, 5 if<2> 1.5, 7 if≥2); bone fractures (7); bone status at DEXA (0 normal, 3 osteopenic, 5 osteoporotic); cancer (5); depression (3 if BDI>17); other psychiatric illness (5). Annual costs of individual ART regimens were calculated. MFRS was correlated in univariate and multivariate models with all variables. All statistical analyses were carried out using Stata 10.1.Summary of resultsWe enrolled 241 HIV patients, 74.3% males, aged 44.5±9.9y; 19 patients (7.8%) were untreated, 74.8% of treated had undetectable HIV RNA. Mean Nadir CD4 counts were 218±168, 38.5% of patients had an AIDS diagnosis. Mean individual ARV annual cost was 10,976±5,360. Mean MFRS was 28.5±13.9 (4–64). MFRS was significantly higher (p<0.001) in patients with older age, longer duration of HIV infection, lower CD4 nadirs, AIDS diagnosis, lipodistrophy, HCV, smoking, lower education, alcohol/drug abuse, hypertension, carotid plaques, higher Framingham score, diabetes, bone fractures or disorders, depression, alexithymia, and higher ARV costs. In multivariate models, ARV costs were significantly higher in patients with older age, previous AIDS diagnosis, lower CD4 nadir and higher MFRS.ConclusionsMFRS may be a simple and reliable tool to match patients' complexity and ARV costs, deserving further validation on larger samples.
Almost 1/3 of HIV‐infected individuals enter health care late in the course of infection, worsening their prognosis and costs of care. According to the recent European consensus definitions, late presenters are persons presenting with CD4 counts <350/μL, and presenters with advanced HIV disease have CD4 < 200/μL or an AIDS‐event. These latter, in particular, are at high risk of further opportunistic infections or death despite of HAART. We included all patients newly diagnosed with HIV infection at the Infectious Diseases Unit of Pescara from 2006 to present, registered for at least one day of observation. The duration of follow up was plotted for all enrolled patients up to 31/12/2011. Demographic, clinical, virological and immunological data, lines of therapy and outcome of HAART were collected for each patient. We included 140 consecutive patients, 18.6% in 2006, 17.9% in 2011; 76.4% were male, while the average age was 39.3±10.2y. AIDS diagnosis at presentation was for 39.7% (50% in 2006, 41.7% in 2011); 52.7% had advanced HIV disease (CD4 <200/μL, 53.8% in 2006, 70.8% in 2011), 67.2 % were late presenters (CD4 <350/μL, 73.1% in 2006, 79.2% in 2011). The average CD4 counts at enrollment were 313.8±294.1 in 2006, 361.3±263.1 in 2007, 281.8±295.5 in 2008, 238.4±201.6 in 2009, 394.1±183.9 in 2010, 225.7±245.2 in 2011. Eight per cent of patients were HCV coinfected. Heterosexual exposure occurred in 54% of patients, homosexual in 36%; drug addiction in 7.5%. Among enrollees, 71.4% were Italian, 18.6% from sub‐Saharan Africa, 5.7% from South America and 4.2% from Eastern Europe. With a median follow up of 2.5 years, 105 patients (75%) were still being treated as of November 30th, 2011; among these 104 (99.1%) were in virological suppression. Among the 35 patients no longer followed, 15 (11.4%) died during the first 6 months of treatment, 20 (14.3%) were lost in the first 6 months of follow‐up. All 15 deaths occurred in patients enrolled with CD4 <200/μL. After initiation of HAART only 1 patient (0.7%) switched for virological failure, 19 (13.6%) for toxicity or simplification. The proportion of late presenters at our center is high (67.2%) in the absence of appropriate local screening measures. Early mortality after diagnosis is similarly high, concentrated in patients with late presentation. Retention in care after 6 months and virological success of treated patients appear very promising, much more than recently reported in North America.
IntroductionHIV‐infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma (KS), non‐Hodgkin's lymphoma (NHL), primary CNS lymphoma (PCL) and invasive cervical cancers are considered AIDS‐defining. An increased incidence in recent years, however, has been reported also for other malignancies after the introduction of HAART.MethodsWe performed a case‐control study to characterize all HIV‐infected patients with both AIDS and non‐AIDS‐defining neoplasms observed among all consecutive patients followed at the Infectious Diseases Unit of Pescara General Hospital, since 1991 through 2012. All cases were matched with equinumerous controls without neoplasia homogeneous for age, sex and AIDS diagnosis.ResultsOut of 626 patients consecutively assisted since 1991, 57 cases of malignancy (9.1%) were observed. Of these, 45 (79.0%) occurred in males; mean age was 43.6±9.3 years; 49 (86.0%) patients were diagnosed with AIDS. Tumors observed were: NHL, 17 (29.8%); SK, 13 (22.8%); HCC, 5 (8.8%); CPL, 6 (10.5%); Hodgkin's lymphoma, 4 (7.0%); solid tumors, 12 (21.1%), including 1 AIDS‐defining tumor (anal cancer). Among these, 37 (66.1%) patients died; of them 14 (37.8%) had non‐AIDS cancers. Cases were well matched with the 55 controls for sex (p=0.9), age (p=0.6) and AIDS diagnosis (p=0.6). In comparison with controls, CD4 nadirs were not different (153±151 in controls vs 136±154 cells/mmc), while CD4 at tumor diagnosis were very different between controls (463±283 cells/mmc) and cases (226±209 cells/mmc, p<0.0001). Among patients with malignancies, those who died had a non‐significant reduction in CD4 counts (p=0.14); seemingly irrelevant were smoking status (p=0.9), working ability (p=0.4), HCV coinfection (p=0.4). Surprisingly, in patients co‐infected with HBV, including HBsAg negative, antibody‐positive subjects, tumors were significantly more frequent (60.7% vs. 38.8%, p=0.009).ConclusionFactors potentially relevant for carcinogenesis in the prolonged survival patients of the HAART era may include HBV coinfection in spite of the lack of active biochemical activity (HbsAg negative) in the majority of coinfected patients. The potential relevance of this finding deserves prompt assessment in a larger multicentric cohort.
Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. Funding National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.
Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long- term investment in surge capacity for acute care during public health emergencies to protect elective staff and services. Funding National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.