Summary Fouchier et al. reported the isolation and genome sequencing of a novel coronavirus tentatively named “human betacoronavirus 2c EMC/2012 (HCoV-EMC)” from a Saudi patient presenting with ...pneumonia and renal failure in June 2012. Genome sequencing showed that this virus belongs to the group C species of the genus betacoronavirus and phylogenetically related to the bat coronaviruses HKU4 and HKU5 previously found in lesser bamboo bat and Japanese Pipistrelle bat of Hong Kong respectively. Another patient from Qatar with similar clinical presentation and positive RT-PCR test was reported in September 2012. We compare and contrast the clinical presentation, laboratory diagnosis and management of infection due to this novel coronavirus and that of SARS coronavirus despite the paucity of published information on the former. Since 70% of all emerging infectious pathogens came from animals, the emergence of this novel virus may represent another instance of interspecies jumping of betacoronavirus from animals to human similar to the group A coronavirus OC43 possibly from a bovine source in the 1890s and the group B SARS coronavirus in 2003 from bat to civet and human. Despite the apparently low transmissibility of the virus at this stage, research preparedness against another SARS-like pandemic is an important precautionary strategy.
The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal ...cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta‐analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting s were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty‐one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta‐analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67–0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70–0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67–0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00–2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00–2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.
What's new?
The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy alone, radiotherapy alone or chemoradiotherapy) for esophageal cancer patients are still not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, here the authors performed a Bayesian network meta‐analysis of 31 randomized controlled trials. Neoadjuvant chemoradiotherapy followed by surgery showed a statistically significant survival advantage over neoadjuvant radiotherapy, neoadjuvant chemotherapy and surgery alone. The results of this analysis support a more pronounced use of multimodal neoadjuvant therapies for the treatment of locally advanced, resectable esophageal cancer.
Purpose
Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT
3
RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of ...chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT
3
RAs in CINV prophylaxis.
Methods
A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT
3
RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT
3
RA-related adverse events.
Results
Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT
3
RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.
Conclusions
Palonosetron is safer and more efficacious than other 5-HT
3
RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.
The D225G (aspartic acid to glycine) substitution in the hemagglutinin of H1N1 influenza virus may alter its receptorbinding specificity. Direct analysis of polymorphisms in 126 amino acids spanning ...the receptor-binding site in the hemagglutinin of pandemic H1N1 2009 virus from 117 clinical specimens in Hong Kong found the D225G substitution for 7 (12.5%) of 57 patients with severe disease and for 0 (0%) of 60 patients with mild disease. D225G quasispecies were identified mainly in endotracheal aspirate samples and were identified less frequently in nasopharyngeal aspirate samples from patients with severe disease. Continuous monitoring of the prevalence and tissue tropism of this variant during its circulation among humans is important.
Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated ...with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be emphasized in the investigation of disease outbreaks in human and animals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Socioeconomic factors influence patterns of care in colorectal cancer. Our study investigates the impact of socioeconomic status (SES) on stage at presentation, receipt of diagnostic imaging, receipt ...of treatment and overall survival (OS) in a universal healthcare system. The Ontario Cancer Registry (OCR) was accessed to identify a cohort of patients diagnosed with colorectal adenocarcinoma from 2007 to 2016 in Ontario, Canada. SES was measured using median neighborhood income divided into quintiles (Q1‐Q5; Q1 = lowest income). Logistic regression analyses were used to evaluate stage, imaging and treatment. Cox proportional hazards models were used to evaluate OS. All endpoints were adjusted for demographics and comorbidities with OS models also adjusting for stage, imaging and treatment. In total, 39 802 colon and 13 164 rectal patients were identified. Lower SES was associated with advanced stage at presentation in both cohorts (Q1 vs Q5: Colon odds ratio OR = 1.08, P = .046, rectal OR = 1.25, P < .0001). Lower SES colon patients were less likely to receive adjuvant oxaliplatin (Q1 vs Q5: OR = 0.78, P < .001) and all palliative chemotherapies studied including oxaliplatin (Q1 vs Q5: OR = 0.60, P < 0.0001), irinotecan (Q1 vs Q5: OR = 0.65, P < .0001), bevacizumab (Q1 vs Q5: OR = 0.70, P < .001), cetuximab (Q1 vs Q5: OR = 0.40, P = .0053) and panitumumab (Q1 vs Q5: OR = 0.54, P = .0036). In rectal patients, lower SES was associated with decreased receipt of rectal cancer resection for stages I‐III (Q1 vs Q5: OR = 0.78, P < .001), adjuvant oxaliplatin (Q1 vs Q5: OR = 0.72, P = .0020) and palliative chemotherapies including oxaliplatin (Q1 vs Q5: OR = 0.59, P < .001), irinotecan (Q1 vs Q5: OR = 0.53, P < .001) and bevacizumab (Q1 vs Q5: OR = 0.71, P = .046). All survival models identified poorer OS for lower SES patients (total colorectal; Q1 vs Q5: Hazard ratio HR = 1.25, P < .0001). These findings suggest disparities persist even within universal healthcare.
What's new?
The impact of socioeconomic status on whether patients receive the full range of diagnostic imaging modalities and treatment options in both colon and rectal cancer remains to be fully determined. Furthermore, few studies have explored overall survival disparities after adjusting for such imaging/treatment variables. This population‐based retrospective study demonstrates that disparities persist across patterns of care in colorectal cancer, even within a single‐payer universal healthcare system. These results provide the basis for further research identifying temporal trends, root causes of inequities, and actionable policies.
Hepatocellular carcinoma (HCC) presentation is heterogeneous necessitating a variety of therapeutic interventions with varying efficacies and associated prognoses. Poor prognostic patients often ...undergo non-curative palliative interventions including transarterial chemoembolization (TACE), sorafenib, chemotherapy, or purely supportive care. The decision to pursue one of many palliative interventions for HCC is complex and an economic evaluation comparing these interventions has not been done. This study evaluates the cost-effectiveness of non-curative palliative treatment strategies such as TACE alone or TACE+sorafenib, sorafenib alone, and non-sorafenib chemotherapy compared with no treatment or best supportive care (BSC) among patients diagnosed with HCC between 2007 and 2010 in a Canadian setting. Using person-level data, we estimated effectiveness in life years and quality-adjusted life years (QALYs) along with total health care costs (2013 US dollars) from the health care payer's perspective (3% annual discount). A net benefit regression approach accounting for baseline covariates with propensity score adjustment was used to calculate incremental net benefit to generate incremental cost-effectiveness ratio (ICER) and uncertainty measures. Among 1,172 identified patients diagnosed with HCC, 4.5%, 7.9%, and 5.6%, received TACE alone or TACE+sorafenib, sorafenib, and non-sorafenib chemotherapy clone, respectively. Compared with no treatment or BSC (81.9%), ICER estimates for TACE alone or TACE+sorafenib was $6,665/QALY (additional QALY: 0.47, additional cost: $3,120; 95% CI: -$18,800-$34,500/QALY). The cost-effectiveness acceptability curve demonstrated that if the relevant threshold was $50,000/QALY, TACE alone or TACE+sorafenib, non-sorafenib chemotherapy, and sorafenib alone, would have a cost-effectiveness probability of 99.7%, 46.6%, and 5.5%, respectively. Covariates associated with the incremental net benefit of treatments are age, sex, comorbidity, and cancer stage. Findings suggest that TACE with or without sorafenib is currently the most cost-effective active non-curative palliative treatment approach to HCC. Further research into new combination treatment strategies that afford the best tumor response is needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with head and neck cancer manage a variety of symptoms at home on an outpatient basis. Clinician review alone often leaves patient symptoms undetected and untreated. Standardized symptom ...assessment using patient-reported outcomes (PROs) has been shown in randomized clinical trials to improve symptom detection and overall survival, although translation into real-world settings remains a challenge.
To better understand how patients with head and neck cancer cope with cancer-related symptoms and to examine their perspectives on standardized symptom assessment.
This was a qualitative analysis using semistructured interviews of patients with head and neck cancer and their caregivers from November 2, 2020, to April 16, 2021, at a regional tertiary center in Canada. Purposive sampling was used to recruit a varied group of participants (cancer subsite, treatment received, sociodemographic factors). Drawing on the Supportive Care Framework, a thematic approach was used to analyze the data. Data analysis was performed from November 2, 2020, to August 2, 2021.
Patient perception of ambulatory symptom management and standardized symptom assessment.
Among 20 participants (median range age, 59.5 33-74 years; 9 45% female; 13 65% White individuals), 4 themes were identified: (1) timely physical symptom management, (2) information as a tool for symptom management, (3) barriers to psychosocial support, and (4) external factors magnifying symptom burden. Participants' perceptions of standardized symptom assessment varied. Some individuals described the symptom monitoring process as facilitating self-reflection and symptom detection. Others felt disempowered by the process, particularly when symptom scores were inconsistently reviewed or acted on.
This qualitative analysis provides a novel description of head and neck cancer symptom management from the patient perspective. The 4 identified themes and accompanying recommendations serve as guides for enhanced symptom monitoring.
Background
Although increasing evidence has suggested that an efficacy‐effectiveness gap exists between clinical trial (CT) and real‐world evidence (RWE), to the authors' knowledge, the magnitude of ...this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies.
Methods
Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population‐based databases. The efficacy‐effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1‐year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan‐Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates.
Results
Twenty‐nine indications from 20 systemic therapies were included. Twenty‐eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0‐12.1 months). Lower effectiveness in RWE also was demonstrated through a meta‐analysis of an OS hazard ratio of 1.58 (95% CI, 1.39‐1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%‐22%).
Conclusions
An efficacy‐effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2‐month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real‐world decision making regarding the use of cancer systemic therapies.
Through a review of clinical trial and real‐world evidence for contemporary cancer systemic therapies, an efficacy‐effectiveness gap has been demonstrated. Thus, supportive evidence is provided in the current study for the further investigation of real‐world outcomes of patients to inform real‐world decision making.
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