Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis.

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Oral Squamous Cell Carcinoma Associated with Precursor Lesions.

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.

Short-term mortality from HIV-infected persons diagnosed from 2012 to 2016: Impact of late diagnosis of HIV infection.

ABSTRACT: We investigated the temporal trends of short-term mortality (death within 1 year of diagnosis) and cause-specific deaths in human immunodeficiency virus (HIV)-infected persons by stage of HIV infection at diagnosis. We also assessed the impact of late diagnosis (LD) on short-term mortality.Epidemiological records of HIV-infected Singapore residents from the National HIV Registry were linked to death records from the Registry of Births and Deaths for observational analyses. Newly-diagnosed HIV cases with available cluster of differentiation 4 count at time of diagnosis in a 5-year period from 2012 to 2016 were included in the study. Hazard ratios (HRs) and 95% confidence interval (CI) of LD for all deaths excluding suicides and self-inflicted or accidental injuries, and HIV/ acquired immunodeficiency syndrome (AIDS)-related deaths occurring within 1 year post-diagnosis were calculated using Cox proportional hazards regression models with adjustment for age at HIV/AIDS diagnosis. Population attributable risk proportions (PARPs) were then calculated using the adjusted HRs.Of the 1990 newly-diagnosed HIV cases included in the study, 7.2% had died by end of 2017, giving an overall mortality rate of 2.16 per 100 person-years (PY) (95% CI 1.82-2.54). The mortality rate was 3.81 per 100 PY (95% CI 3.15-4.56) in HIV cases with LD, compared with 0.71 (95% CI 0.46-1.05) in non-LD (nLD) cases. Short-term mortality was significantly higher in LD (9.1%) than nLD cases (1.1%). Of the 143 deaths reported between 2012 and 2017, 58.0% were HIV/AIDS-related (nLD 28.0% vs LD 64.4%). HIV/AIDS-related causes represented 70.4% of all deaths which occurred during the first year of diagnosis (nLD 36.4% vs LD 74.7%). The PARP of short-term mortality due to LD was 77.8% for all deaths by natural causes, and 87.8% for HIV/AIDS-related deaths.The mortality rate of HIV-infected persons with LD was higher than nLD, especially within 1 year of diagnosis, and HIV/AIDS-related causes constituted majority of these deaths. To reduce short-term mortality, persons at high risk of late-stage HIV infection should be targeted in outreach efforts to promote health screening and remove barriers to HIV testing and treatment.

Modeling the Impact of Delaying the Diagnosis of Non-Small Cell Lung Cancer During COVID-19.

BACKGROUND: The novel coronavirus (COVID-19) pandemic has led surgical societies to recommend delaying diagnosis and treatment of suspected lung cancer for lesions less than 2 cm. Delaying diagnosis can lead to disease progression, but the impact of this delay on mortality is unknown. The COVID-19 infection rate at which immediate operative risk exceeds benefit is unknown. We sought to model immediate versus delayed surgical resection in a suspicious lung nodule less than 2 cm. METHODS: A decision analysis model was developed, and sensitivity analyses performed. The base case was a 65-year-old male smoker with chronic obstructive pulmonary disease presenting for surgical biopsy of a 1.5 to 2 cm lung nodule highly suspicious for cancer during the COVID-19 pandemic. We compared immediate surgical resection to delayed resection after 3 months. The likelihood of key outcomes was derived from the literature where available. The outcome was 5-year overall survival. RESULTS: Immediate surgical resection resulted in a similar but slightly higher 5-year overall survival when compared with delayed resection (0.77 versus 0.74) owing to the risk of disease progression. However, if the probability of acquired COVID-19 infection is greater than 13%, delayed resection is favorable (0.74 vs 0.73). CONCLUSIONS: Immediate surgical biopsy of lung nodules suspicious for cancer in hospitals with low COVID-19 prevalence likely results in improved 5-year survival. However, as the risk of perioperative COVID-19 infection increases above 13%, a delayed approach has similar or improved survival. This balance should be frequently reexamined at each health care facility throughout the curve of the pandemic.

Primary anaplastic large cell lymphoma of the central nervous system in a child: A case report.

INTRODUCTION: To report the clinical characteristics of primary central nervous system T-cell lymphoma with anaplastic lymphoma kinase-1 (ALK-1) positive in an 8-year-old male. PATIENT CONCERNS: The patient presented cognitive impairment, dizziness, vomiting, fever, and convulsions during the disease, followed by progressive and persistent severe headache, progressive increase of intracranial pressure, indifference, disorder of consciousness, mild increase in white blood cells in cerebrospinal fluid, progressive decrease of sugar, progressive increase of protein, abnormal signal of left parietal-occipital, local meningeal enhancement, and cerebrospinal fluid cytology. DIAGNOSIS: He was diagnosed with ALK-1-positive central nervous system T-cell lymphoma. INTERVENTIONS: Meropenem and vancomycin were administered to counter the infection, while dexamethasone alleviated the inflammation. OUTCOMES: The patient died of cerebral hernia due to intracranial hypertension in the eighth week of the disease. CONCLUSIONS: PCNS ALK-1-positive anaplastic large cell lymphoma is extremely rare. Also, it is difficult to distinguish from central meningeal lymphoma and central nervous system infection, which might lead to delayed diagnosis. However, early diagnosis depends on the pathological diagnosis of brain tissue biopsy.

Delay in diagnosing patients with right-sided glioblastoma induced by hemispheric-specific clinical presentation.

PURPOSE: Cognitive functions are differentially represented in brain hemispheres. Aphasia is an "easy to recognize" symptom of diseases affecting the left side. In contrast, lesions in the right hemisphere cause subtle neuropsychological deficits such as neglect and anosognosia. We evaluated whether right-sided malignant brain tumors are on average larger at the time of first diagnosis as compared to left-sided tumors, and extrapolated the delay in diagnosing right-sided tumors compared to the left side. METHODS: All first-ever diagnosed glioblastoma (GBM) patients between 2005 and 2012 were identified using our hospital-based prospective research registry. Baseline data, information on initial clinical presentation and imaging findings (including tumor volume) were collected. Extrapolation of time since tumor initiation was based on an established gompertzian growth model. RESULTS: We included 173 patients. Mean age of the study population was 58 ± 13 years. Tumors located in the right hemisphere (n = 96) were larger as compared to tumors located in the left hemisphere (n = 77) (median 36.4 mL [interquartile range 13.0-56.0; minimum 0.2, maximum 140.0] vs. 17.2 mL [7.7-45.1 mL; 0.4, 105.2]; p = 0.011). Right-sided tumors grew longer than left-sided tumors (378 ± 95 days vs. 341 ± 74 days; p = 0.006). Initial neuropsychological symptoms differed depending on the affected hemisphere. CONCLUSION: Right-hemispheric symptoms appear to be less clinically conspicuous resulting in a delayed diagnosis of GBM, which might be improved by raising awareness for the corresponding neuropsychological deficits. Whether our findings have prognostic implications needs to be evaluated in future studies.

Temporal Trends in the Characteristics, Management and Outcomes of Patients With Acute Coronary Syndrome According to Their Killip Class.

Based on the historical Killip Classification, higher Killip class is associated with increased mortality in patients with acute coronary syndrome (ACS), yet data on current prognosis are lacking. We sought to examine temporal trends in the management and outcomes of patients admitted with an ACS by Killip class and to assess its contemporary prognostic value. Time-dependent analysis (early-period 2000 to 2008 vs late-period 2010 to 2016) in patients with lower (=1) and higher (≥2) Killip classes in a national ACS survey. Clinical outcomes included 30d MACE (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Included were 9,736 and 5,288 patients in the early and late time-periods of which 18.5% and 11.5% were categorized as higher Killip class, respectively (p <0.001). Baseline co-morbidities (diabetes, hypertension, dyslipidemia) were more prevalent in the late versus early time periods in both study groups (p <0.001). Rates of 30d MACE decreased in both Killip classes (p <0.001), yet 1-year mortality decreased only in patients with lower Killip class (p = 0.02), and remained extremely high (30%) in patients with higher Killip class (p = 0.75). Killip class was a significant independent predictor for 1-year mortality, both in the early (adjusted hazard ratio 3.23, confidence interval 2.8, 3.7) and late (adjusted hazard ratio 4.13, confidence interval 3.21, 5.32) time periods. In conclusion, even in the current era, patients presenting with ACS and higher Killip class have poor 1-year survival. Efforts should focus on improving the adherence to guideline-recommended therapies. The Killip classification system is still a reliable prognostic tool.

Comparison of Outcomes in Patients With Acute Coronary Syndrome Presenting With Typical Versus Atypical Symptoms.

Although typical chest pain is an important clinical feature required for diagnosis of acute coronary syndrome (ACS), many patients present with atypical complaints. The full extent and implication of this presentation is largely unknown. The study aim was to evaluate possible relations and temporal trends between presenting symptoms and outcomes in patients with ACS. Data was obtained from the Acute Coronary Syndrome Israeli Survey on patients presenting with typical chest pain versus atypical complaints, including dyspnea, nonspecific chest pain, palpitations or other. Temporal trends analysis examined the early (2000 to 2006) versus the late (2008 to 2016) period. During 2000 to 2016, 14,722 patients with ACS were enrolled; 11,508 (79%) presented with typical chest pain and 3,214 (21%) with atypical complaints. Patients with atypical complaints were older, majority female, and had more co-morbidities (p <0.001 for each). The 30-day major adverse cardiac events, 30-day mortality, and 1-year mortality rate were significantly higher in patients presenting with atypical complaints, (18% vs 13.5%, 7.7% vs 3.6%, and 15.6% vs 7.5%, respectively, p <0.001 for each). Although 1-year mortality decreased significantly over the years in patients with typical chest pain, there were no significant changes in patients who presented with atypical complaints. These results were consistent in STEMI and non-STE-ACS patients. In conclusion, ACS patients who present with atypical complaints have a less favorable outcome compared with patients who present with typical chest pain, and failed to show an improvement in mortality over the past 2 decades. Identification and utilization of guideline-recommended therapies in these high-risk patients may improve their future outcome.

How European primary care practitioners think the timeliness of cancer diagnosis can be improved: a thematic analysis.

BACKGROUND: National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. OBJECTIVES: This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. DESIGN: In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. SETTING: A primary care study, with participating centres in 20 European countries. PARTICIPANTS: A total of 1352 PCPs answered the final survey question, with a median of 48 per country. RESULTS: The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. CONCLUSIONS: To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission.

BACKGROUND: Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. METHODS: This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. RESULTS: Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). CONCLUSIONS: Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

Health impact of delayed implementation of cervical cancer screening programs in India: A modeling analysis.

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual-based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age-specific cancer incidence and mortality reductions associated with screening (once-in-a-lifetime among women aged 30-34 years) with one-visit visual inspection with acetic acid (VIA) and one- and two-visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one-visit VIA, two-visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point-of-care one-visit HPV testing in 5 years; and (3) 5-year delayed implementation of screening with current screening tests or point-of-care HPV testing. Immediate implementation of two-visit HPV testing with a switch to one-visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30- to 34-year-old women screened once between 2017 and 2026. Delayed implementation with a one-visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high-burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination.

Delays in Diagnosis of Pediatric Histologically Confirmed Sellar Germ Cell Tumors in China: A Retrospective Risk Factor Analysis.

BACKGROUND: Sellar germ cell tumors (GCTs) occur more frequently in childhood. Some will present as malignancy with infiltration and metastasis. However, the association between the timeliness of diagnosis and outcome has been controversial. We investigated the clinical risk factors associated with a diagnostic delay in patients with sellar GCTs in China. METHODS: The data from 53 patients aged <18 years with histologically confirmed sellar GCTs at Peking Union Medical College Hospital treated from January 2008 to December 2016 were reviewed retrospectively. RESULTS: The median interval between symptom onset and diagnosis was 25 months. Of the 53 patients, 44 (83%) had a delayed diagnosis. Most patients (86%) with a delayed diagnosis presented with polyuria or polydipsia. Of the 53 patients, 48 (91%) exhibited changes in the pituitary stalk. Patients with a germinoma (odds ratio, 4.1; 95% confidence interval, 2.4-6.9) and slow growth (odds ratio, 5.3; 95% confidence interval, 1.2-24.5) were more likely to have a delayed diagnosis. The overwhelming majority of patients with a delayed diagnosis (96%) had been seen by >1 doctor. No statistically significant differences were found in the mean survival time (P = 0.21) or mean progression-free survival time (P = 0.36) between patients with and without delay in diagnosis, respectively. CONCLUSIONS: A significant proportion of patients with sellar GCTs will experience a delay in the time to diagnosis. Although a delay in diagnosis did not reduce the survival time or progression-free survival time for patients with sellar GCTs, it might increase the risk of short stature. Thus, a detailed medical history and an immediate radiological examination are important for the early diagnosis of sellar GCTs in childhood.

Homeless With Cancer: An Unrecognized Problem in the United States.

Homelessness is a national problem that is worsening. Some challenges the homeless face-lack of shelter, food, health care, support, and opportunities-are well known. Cancer, an unrecognized problem among the homeless, is a leading cause of their deaths.

Improved survival of head and neck cancer patients in Greenland.

Previously, head and neck cancer (HNC) patients in Greenland have had significant diagnostic delay and poor survival rates. From 2005-2009 several initiatives have been made to ensure faster diagnosis and better survival. The aim of this study was to compare the prognosis before and after these initiatives were introduced. All Greenlandic patients diagnosed with HNC between 2005 and 2012 were included. Data were retrieved from medical records and national databases and compared with the period 1994-2003. A total of 98 patients were identified. Diagnostic delay was significantly lower compared to the period 1994-2004 (p=0.048). The 3-year overall survival was 56% for all HNC and 47% for nasopharyngeal carcinomas. We found that patients with HNC between 1994 and 2003 had a higher risk of death from all reasons compared with the period 2005-2012 (HR 2.17; CI 1.46-3.23) after adjustments for stage and diagnostic delay. Patients with head HNC in Greenland from 2005-2012 were diagnosed earlier and had a better overall survival compared to the period 1994-2003. The change in survival is more likely to be due to improvement in treatment rather than the initiated interventions. Although survival has improved in Greenland, demographic problems and lack of specialists remain a challenge.

[Is the fight against maternal mortality in Burkina Faso adapted to reduce the three delays?]. / La lutte contre la mortalité maternelle au Burkina Faso est-elle adaptée pour réduire les trois retards?

OBJECTIVE: Maternal mortality remains high in Burkina Faso despite numerous interventions designed to reduce this mortality. It therefore appeared important to analyse attempts to lower maternal mortality in Burkina Faso over the last fifteen years in order to identify the strengths and weaknesses and to improve the national programme. METHODS: Analysis according to the ?three delays? model using the strengths, weaknesses, opportunities and threats method was conducted. Data sources were scientific publications as well as national gray literature. RESULTS: Many studies have identified factors predisposing to the first delay, but very few effective interventions covering all of the country have been conducted to reduce this delay. The development of infrastructures, a rapid transfer system and integration of the cost of transfer into the cost of delivery subsidy were interventions designed to reduce the second delay. The promotion of blood transfusion, emergency obstetric and neonatal care, an increased number of trained health professionals, delegation of tasks, subsidy and then free delivery costs were interventions designed to reduce the third delay. The analysis globally demonstrated that interventions on the first delay were insufficient and rarely implemented and weaknesses were observed in relation to the intervention designed to act on the last two delays. CONCLUSION: Due to their inadequacy and poor quality, the interventions failed to significantly reduce the three delays. Priority needs to be given to new interventions, especially community-based interventions, and reinforcement of the quality of care by health training.