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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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (©2021 American Association for Cancer Research.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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.

We present a case with extremely late diagnosis of type II hereditary angioedema (HAE). Given recent advances in HAE treatment, we want to bring physician awareness to this condition and aid in earlier detection. HAE is a disorder associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. Late diagnosis of HAE can lead to significant morbidity and is severely impairing due to recurring attacks. The diagnosis of HAE is ordinarily made during childhood and adolescence. Delayed diagnoses in early and middle adulthood have been documented in the literature. Gastrointestinal symptoms are common features of HAE and can be misdiagnosed as disease of primary gastrointestinal pathology, such as irritable bowel syndrome, recurrent pancreatitis, or appendicitis. These attacks are characterized by recurrent attacks of subcutaneous and submucosal edema without the presence of urticaria.We present a case of an elderly veteran whose diagnoses was extremely delayed into the eighth decade of life subsequent to unexplained abdominal symptoms. After diagnosis, the patient's symptoms were well controlled with medication due to advances in HAE treatment. To prevent further atypically delayed diagnoses, physicians should consider HAE in patients with recurrent attacks of unexplained abdominal pain.

Theoretically, time from breast cancer diagnosis to therapeutic surgery should affect survival. However, it is unclear whether this holds true in a modern healthcare setting in which breast cancer surgery is carried out within weeks to months of diagnosis. This is a population- and register-based study of all women diagnosed with invasive breast cancer in the Stockholm-Gotland healthcare region in Sweden, 2001-2008, and who were initially operated. Follow-up of vital status ended 2014. 7,017 women were included in analysis. Our main outcome was overall survival. Main analyses were carried out using Cox proportional hazards models. We adjusted for likely confounders and stratified on mode of detection, tumor size and lymph node metastasis. We found that a longer interval between date of morphological diagnosis and therapeutic surgery was associated with a poorer prognosis. Assuming a linear association, the hazard rate of death from all causes increased by 1.011 (95% CI 1.006-1.017) per day. Comparing, for example, surgery 6 weeks after diagnosis to surgery 3 weeks after diagnosis, thereby confers a 1.26-fold increased hazard rate. The increase in hazard rate associated with surgical delay was strongest in women with largest tumors. Whilst there was a clear association between delays and survival in women without lymph node metastasis, the association may be attenuated in subgroups with increasing number of lymph node metastases. We found no evidence of an interaction between time to surgery and mode of detection. In conclusion, unwarranted delays to primary treatment of breast cancer should be avoided., (© 2018 UICC.)

Background: Delays to surgery for patients requiring an acute operation are associated with increased morbidity and mortality. A recent study from our institution observed long waiting times for patients booked for an acute operation. The aim of this study was to evaluate the patient's progress from presentation to arrival in the operating theatre and to identify where delays occurred., Methods: Patients undergoing acute general surgery between July 2016 and May 2017 were studied. Data were obtained for time of presentation, imaging, theatre and booking. A time interval from presentation to booking for theatre of greater than 6 h was defined as a diagnostic delay. A time interval from booking to theatre greater than the category defined time (four-level priority system) was defined as a logistic delay., Results: A total of 683 patients were included. A diagnostic delay was observed in 55.1%. This occurred more frequently in patients who required imaging prior to their operation (82.5 versus 41.1%, P < 0.001). Logistic delay occurred in 31.0% of the patients, and this was most common for patients booked as a category 3 (requiring surgery within 6 h, 41.8%, P < 0.001). Patients who had a diagnostic delay were significantly more likely to have a post-operative complication compared to patients who did not (17.2 versus 10.0%, P = 0.009)., Conclusion: There are significant delays associated with patients presenting to the acute general surgery service and their transition to theatre. Addressing both the diagnostic and the logistic delays in our institution should result in a significant improvement in patient care., (© 2018 Royal Australasian College of Surgeons.)

Prostate Cancer (CaP) is the most commonly diagnosed cancer among Cameroonian men. Due to inadequate infrastructure, record keeping, and resources, little is known about its true burden on the population. There are rural/urban disparities with regards to awareness, screening, treatment, and survivorship. Furthermore, use of traditional medicine and homeopathic remedies is widespread, and some men delay seeking conventional medical treatment until advanced stages of CaP. This study examined the perceptions, beliefs, and practices of men in Cameroon regarding late stage CaP diagnoses; identified factors that influence screening decision; and ascertained how men decided between traditional or conventional medicine for CaP diagnosis and treatment. Semistructured focus groups were used to collect data from men in Bamenda, Cameroon. Qualitative data analysis was used to analyze transcripts for emerging themes and constructs using a socio-ecological framework. Twenty-five men participated in the study, with an average age of 59. Most of the participants had never received a prostate screening recommendation. Socioeconomic status, local beliefs, knowledge levels, awareness of CaP and screening methods, and stigma were prominent themes. A significant number of Cameroonian men receive late stage CaP diagnosis due to lack of awareness, attitudes, cultural beliefs, self-medication, and economic limitation. To effectively address these contributing factors to late stage CaP diagnosis, a contextually based health education program is warranted and should be tailored to fill knowledge gaps about the disease, dispel misconceptions, and focus on reducing barriers to utilization of health services.

Background: Limited data exist on whether early colonoscopy for lower gastrointestinal bleeding (LGIB) alters 30-day mortality, performance of endoscopic intervention, or need for blood transfusion. Our primary objective was to determine whether early colonoscopy in LGIB is associated with decreased 30-day mortality using a large hospital administrative database., Methods: Patients hospitalized between January 2008 and September 2015 were identified using a validated, machine learning algorithm for identifying patients with LGIB. "Early" colonoscopy occurred by day 2 of admission and "late" colonoscopy between days 3 and 5. A propensity score for early colonoscopy was constructed using plausible confounders. Univariable and multivariable logistic regression were used to determine factors associated with 30-day mortality, endoscopic intervention, and transfusion need. The propensity score was included as a confounding factor for mortality analysis in the multivariable model., Results: In total, 1204 patients underwent colonoscopy for LGIB. Of these, 295 patients (25%) underwent early colonoscopy, and these patients had a lower Charlson Comorbidity Index (P=0.001) and shorter length of stay (3 vs. 5 d, P=0.0001). Early colonoscopy was not associated with decreased 30-day mortality [odds ratio (OR), 0.73; confidence interval (CI), 0.27-1.69], but was associated with increased endoscopic intervention (OR, 2.62; CI, 1.37-4.95) and decreased need for transfusion (OR, 0.65; CI, 0.49-0.87). On multivariable analysis adjusting for timing of colonoscopy, age, and propensity score for early colonoscopy, early colonoscopy was not associated with a decrease in 30-day mortality (OR, 1.37; CI, 0.50-3.79)., Conclusions: Early colonoscopy does not affect 30-day mortality but may allow for earlier endoscopic intervention and decreased transfusion need.

Background: Rocky Mountain spotted fever (RMSF) is potentially deadly and can present subtly with signs and symptoms overlapping with other clinical conditions. Delayed diagnosis can be fatal., Objective: This review provides an evidence-based summary of the current data for the evaluation and management of RMSF in the emergency department., Discussion: RMSF occurs through transmission of Rickettsia rickettsii by an infected tick. Exposure in the United States occurs most commonly from April to September, and high-risk locations include wooded, shrubby, or grassy areas. Approximately half of patients with infection do not recall tick exposure. Symptoms can include fever, headache, photophobia, malaise, myalgias, and a petechial rash that begins on the wrists and ankles and spreads to the trunk. Rash may not occur in ≤15% of patients, and the classic triad of fever, headache, and rash is also not definitive. Laboratory evaluation may demonstrate hyponatremia, anemia, thrombocytopenia, abnormal liver enzymes, and elevated coagulation tests. Antibody testing can be helpful, but these results are not typically available to the emergency clinician. Doxycycline is the treatment of choice in adults, children, and pregnant patients. Patients should be advised about prevention strategies and effective techniques for removing ticks., Conclusions: RMSF is a potentially deadly disease that requires prompt recognition and management. Focused history, physical examination, and testing are important in the diagnosis of this disease. Understanding the clinical features, diagnostic tools, and proper treatment can assist emergency clinicians in the management of RMSF., (Published by Elsevier Inc.)

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.

Background: Non-ST elevation myocardial infarction (NSTEMI) is a common manifestation of acute coronary syndrome (ACS), but delayed diagnosis can increase mortality. In this proof of principle study, the emergency physician performed transthoracic echocardiography (TTE) on scene to determine whether NSTEMI could be correctly diagnosed pre-hospitalization. This could expedite admission to the appropriate facility and reduce the delay until initiation of correct therapy., Methods: Pre-hospital TTE was performed on scene by the emergency physician in patients presenting with ACS but without ST-elevation in the initial 12-lead electrocardiography (ECG) (NSTE-ACS). A presumptive NSTEMI diagnosis was made if regional wall motion abnormalities (RWMA) were detected. These patients were admitted directly to a specialist cardiac facility. Patient characteristics and pre-admission and post-admission clinical, pre-hospital TTE data, and therapeutic measures were recorded., Results: Patients with NSTE-ACS (n = 53; 72.5 ± 13.4 years of age; 23 female) were studied. The 20 patients with pre-hospital RWMA and presumptive NSTEMI, and two without RWMA were conclusively diagnosed with NSTEMI in hospital. Percutaneous coronary intervention was performed in 50% of the patients presumed to have NSTEMI immediately after admission. The RWMA seen before hospital TTE corresponded with the in-hospital ECG findings and/or the supply regions of the occluded coronary vessels seen during PCI in 85% of the cases. The diagnostic sensitivity of pre-hospital TTE for NSTEMI was 90.9% with 100% specificity., Conclusions: Pre-hospital transthoracic echocardiography by the emergency physician can correctly diagnose NSTEMI in more than 90% of cases. This can expedite the initiation of appropriate therapy and could thereby conceivably reduce morbidity and mortality., Trial Registration: Deutsche Register klinischer Studien, DRKS00004919 . Registered on 29 April 2013.

Purpose: Despite being generally accepted that delays in diagnosing breast cancer are of prognostic and psychological concern, the influence of hospital characteristics on such delays remains poorly understood, especially in rural and underserved areas. However, hospital characteristics have been tied to greater efficiency and warrant further investigation as they may have implications for breast cancer care in these areas., Methods: Study data were derived from the Kentucky, North Carolina, Ohio, and Pennsylvania state central cancer registries (2006-2008). We then linked Medicare enrollment files and claims data (2005-2009), the Area Resource File (2006-2008), and the American Hospital Association Annual Survey of Hospitals (2007) to create an integrated data set. Hierarchical linear modeling was used to regress the natural log of breast cancer diagnosis delay on a number of hospital-level, demographic, and clinical characteristics., Findings: The baseline study sample consisted of 4,547 breast cancer patients enrolled in Medicare that lived in Appalachian counties at the time of diagnosis. We found that hospitals with for-profit ownership (P < .01) had shorter diagnosis delays than their counterparts. Estimates for comprehensive oncology services, system membership and size were not statistically significant at conventional levels., Conclusions: Some structural characteristics of hospitals (eg, for-profit ownership) in the Appalachian region are associated with having shorter delays in diagnosing breast cancer. Researchers and practitioners must go beyond examining patient-level demographic and tumor characteristics to better understand the drivers of timely cancer diagnosis, especially in rural and underserved areas., (© 2017 National Rural Health Association.)

Background: Cancer during pregnancy is relatively rare but may lead to maternal mortality. We aimed to assess the incidence of cancer related maternal mortality and the neonatal outcome in these patients. Also, doctor- and patient-related delay in cancer diagnosis and therapy among patients with cancer related maternal mortality is assessed., Methods: Maternal mortality was defined as death during pregnancy or within 1 year after delivery. Data of the Dutch Maternal Mortality Committee was used to calculate the cancer related maternal mortality rate and to assess neonatal outcome in the Netherlands. Delay was scored by ten medical specialist based on case descriptions., Results: Cancer related maternal mortality rate was 1.23 per 100,000 live births. Delay in either diagnosis or treatment occurred in 65%. Delay in diagnosis was more frequent then delay in treatment, and was mainly caused by health care providers. Only 77% of pregnancies were ongoing, and 65% ended preterm of which 85% was induced., Conclusions: Avoiding delay in diagnosis and therapy in case of pregnancy related cancer could potentially improve maternal and neonatal outcome. It is therefore essential to increase awareness among health care providers about the occurrence and recurrence of cancer in pregnancy and the possibilities of diagnostic and therapeutic interventions in these women.

Purpose: The aim of this study is to describe the symptoms and signs of central nervous system (CNS) tumors in a pediatric population and to assess the time interval between the onset of the disease and the time of the diagnosis., Methods: A retrospective observational study was conducted at our Oncology Pediatric Unit between January 2000 and November 2011. We included 75 children between 5 months and 16 years (mean age of 7.8 ± 4.7 years), with male to female ratio of 3:2. The tumor localization was supratentorial in 51% of cases, and the most frequent histological type was low-grade astrocytoma (48%)., Results: Presenting symptoms were headache (31%), vomiting (31%), seizures (21%), and behavioral change (11%). The most common symptoms at diagnosis were headache (51%), vomiting (51%), visual difficulties (37%), seizures (24%), and behavioral change (21%). By the time of diagnosis, neurologic examination was altered in 68% of our patients. Vomiting (44%) and behavioral change (44%) were the most frequent symptoms in children under 4 years of age, headache (61%) and vomiting (54%) in children older than 4 years. The median interval between symptoms' onset and diagnosis was 4 weeks (range 0 to 314 weeks). A longer symptom interval was associated with younger age, infratentorial localization and low-grade tumors. The differences in symptom intervals between the different age, location, and grade groups were not statistically significant. Survival probability was influenced by tumor grade but not by diagnostic delay or age of the child., Conclusions: Headache and vomiting are the earliest and commonest symptoms in children with brain tumors. Visual symptoms and signs and behavioral change are often present. Abnormalities in neurological examination are reported in most of the children. Intracranial hypertension symptoms suggest the need for a neurological clinical examination and an ophthalmological assessment.

Objective: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS., Methods: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005. To investigate the time of diagnosis, we compared individuals with and without chronic comorbidity using multinomial logistic regression. To investigate mortality, we used Cox regression with time-dependent covariates, following study participants from clinical MS onset until endpoint (death) or to the end of the study, censuring at emigration., Results: We identified 8,947 individuals with clinical onset of MS between 1980 and 2005. In the study of time of diagnosis, we found statistically significant odds ratios for longer diagnostic delays with cerebrovascular comorbidity (2.01 [1.44-2.80]; <0.0005), cardiovascular comorbidity (4.04 [2.78-5.87]; <0.0005), lung comorbidity (1.93 [1.42-2.62]; <0.0005), diabetes comorbidity (1.78 [1.04-3.06]; 0.035), and cancer comorbidity (2.10 [1.20-3.67]; 0.009). In the mortality study, we found higher hazard ratios with psychiatric comorbidity (2.42 [1.67-3.01]; <0.0005), cerebrovascular comorbidity (2.47 [2.05-2.79]; <0.0005), cardiovascular comorbidity (1.68 [1.39-2.03]; <0.0005), lung comorbidity (1.23 [1.01-1.50]; 0.036), diabetes comorbidity (1.39 [1.05-1.85]; 0.021), cancer comorbidity (3.51 [2.94-4.19]; <0.0005), and Parkinson disease comorbidity (2.85 [1.34-6.06]; 0.007)., Conclusions: An increased awareness of both the necessity of neurologic evaluation of new neurologic symptoms in persons with preexisting chronic disease and of optimum treatment of comorbidity in MS is critical., (© 2017 American Academy of Neurology.)

Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P <0.001). Patients with host factors for invasive fungal disease were more likely to receive AFT (72.5% vs. 37.4%) as were those with multiorgan failure (SOFA score >7) (68.4% vs. 36.9%) (both P <0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89-2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: The early chain of care is critical for stroke patients. The most important part is the so-called 'system delay' i.e. the delay time from call to the emergency medical services until a diagnosis is established (computer tomography)., Aim: The purpose of this study was to relate the initial priority level given by the dispatch centre to the early chain of care in acute stroke and to short-term and long-term mortality., Methods: All patients hospitalised with the first and the final diagnosis of acute stroke, 15 December 2010-15 April 2011, were recruited across nine hospitals, each hospital with a stroke care unit., Results: In all, 897 stroke patients were included. Priority at the dispatch centre: 54% received highest priority 1, 41% priority 2 and 5% priority 3. Median system delay from call to emergency medical services until diagnosis by computer tomography was 2 h and 52 min, 4 h and 49 min and 6 h and 33 min respectively in the three priority groups ( p<0.0001). There was a similarly strong association between priority level at the dispatch centre and system delay to arrival in a hospital ward, suspicion of stroke by the emergency medical services nurse as well as the physician on hospital admission and the proportion of patients given thrombolysis. Mortality during the subsequent 30 days was 22% among patients with priority 1 and 14% among patients with priority 2., Conclusion: Patients given a lower priority level at the dispatch centre had the longest system delay. Although many of these patients died, the risk of death was highest among those given the highest priority.

Background: Several studies have reported a survival disadvantage for rural dwellers who develop colorectal cancer, but the underlying mechanisms remain obscure. Delayed presentation to GPs may be a contributory factor, but evidence is lacking., Aim: To examine the association between rurality and travel time on diagnosis and survival of colorectal cancer in a cohort from northeast Scotland., Design and Setting: The authors used a database linking GP records to routine data for patients diagnosed between 1997 and 1998, and followed up to 2011., Method: Primary outcomes were alarm symptoms, emergency admissions, stage, and survival. Travel time in minutes from patients to GP was estimated. Logistic and Cox regression were used to model outcomes. Interaction terms were used to determine if travelling time impacted differently on urban versus rural patients., Results: Rural patients and patients travelling farther to the GP had better 3-year survival. When the travel outcome associations were explored using interaction terms, the associations differed between rural and urban areas. Longer travel in urban areas significantly reduced the odds of emergency admissions (odds ratio [OR] 0.62, P <0.05), and increased survival (hazard ratio 0.75, P <0.05). Longer travel also increased the odds of presenting with alarm symptoms in urban areas; this was nearly significant (OR 1.34, P = 0.06). Presence of alarm symptoms reduced the likelihood of emergency admissions (OR 0.36, P <0.01)., Conclusion: Living in a rural area, and travelling farther to a GP in urban areas, may reduce the likelihood of emergency admissions and poor survival. This may be related to how patients present with alarm symptoms., (© British Journal of General Practice 2017.)

Background: Pediatric cancer is rare and its symptoms are often ambiguous. The aims of this study were to investigate the time needed to make a diagnosis, assess the frequency of misdiagnosis, and to determine whether these factors affected survival., Methods: A review of records of 364 pediatric patients diagnosed with cancer at the University of Rochester Golisano Children's Hospital between 2004 and 2012 was conducted. Data were extracted on patient and health care system-related factors and clinical outcomes., Results: The median time from symptom onset to diagnosis was shortest for leukemia (18.5 d) and longest for bone tumors (86.5 d). Tumor type was the only factor associated with time to diagnosis. In 52% of cases an incorrect nononcological diagnosis was initially made. Soft tissue sarcomas and brain tumors were misdiagnosed most often. Neither prolonged time to diagnosis nor initial misdiagnosis was associated with reduced survival. Tumor type and presence of metastatic disease at diagnosis were significantly associated with survival., Conclusions: There is significant variation in the time from symptom onset to diagnosis of pediatric cancers, and incorrect initial diagnostic impressions are common. Despite this there is no impact of prolonged time to diagnosis on survival.

Background: Acute kidney injury (AKI) is a complex syndrome associated with substantial morbidity, mortality and costs. Despite advancements in diagnosis and care practice, AKI remains a disorder usually under/late-recognized with high mortality. One of the hidden reasons for poor outcome might be delayed nephrology consultation, with the involvement of the specialist only in severe stages of AKI when renal replacement therapy (RRT) is required., Methods: We searched PubMed, EMBASE and Cochrane central register for related work on the subject. Six studies were identified for the meta-analysis, correlating time of nephrology consultation and mortality in AKI., Results: We found that delayed nephrology consultation is associated with higher mortality in AKI, with an OR 0.79 (95% CI 0.48-1.10, p < 0.05)., Conclusion: Delayed nephrology consultation contributes to higher mortality in AKI. The early involvement of nephrologist may present an advantage in terms of early recognition, prevention and effective treatment of AKI. An early involvement of multidisciplinary task force may contribute to better treatment, before the preventable complications of AKI occur or an emergency RRT is required., (© 2016 S. Karger AG, Basel.)

This study aimed to present the survival of patients with malignant and paramalignant pleural effusion (MPE) in a context of resource-limited countries. We retrospectively studied patients received for malignant and paramalignant pleural effusion in three health facilities in Ouagadougou from 1st August 2009 to 30 July 2015. Survival was analyzed according to various characteristics related to patients and disease. Eighty patients with a mean age of 54 years were selected. The sex-ratio was 0.9. Sixteen patients had comorbidities. Pleural effusion was revealing, synchronous and metachronous in respectively 55 %, 26.3 % and 17.5 % of cases. Lung cancer was the most common cause of MPE (27.5 %), followed by breast cancer (18.7 %). The median overall survival was 3 months; it varied between primary cancers: 5 months for primary cancer unknown, 4 months for lung cancers and 2 months for breast cancers. Sex and the presence of comorbidities were independent factors influencing survival of patients. In this study, patient survival length is strongly compromised by inadequacies of medical technical equipment., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Disparate and contradictory results make studies necessary to investigate in more depth the relationship between diagnostic delay and survival in colorectal cancer (CRC) patients. The aim of this study is to analyse the relationship between the interval from first symptom to diagnosis (SDI) and survival in CRC., Methods: Retrospective study of n = 942 CRC patients. SDI was calculated as the time from the diagnosis of cancer and the first symptoms of CRC. Cox regression was used to estimate five-year mortality hazard ratios as a function of SDI, adjusting for age and gender. SDI was modelled according to SDI quartiles and as a continuous variable using penalized splines., Results: Median SDI was 3.4 months. SDI was not associated with stage at diagnosis (Stage I = 3.6 months, Stage II-III = 3.4, Stage IV = 3.2; p = 0.728). Shorter SDIs corresponded to patients with abdominal pain (2.8 months), and longer SDIs to patients with muchorrhage (5.2 months) and rectal tenesmus (4.4 months). Adjusting for age and gender, in rectum cancers, patients within the first SDI quartile had lower survival (p = 0.003), while in colon cancer no significant differences were found (p = 0.282). These results do not change after adjusting for TNM stage. The splines regression analysis revealed that, for rectum cancer, 5-year mortality progressively increases for SDIs lower than the median (3.7 months) and decreases as the delay increases until approximately 8 months. In colon cancer, no significant relationship was found between SDI and survival., Conclusions: Short diagnostic intervals are significantly associated with higher mortality in rectal but not in colon cancers, even though a borderline significant effect is also observed in colon cancer. Longer diagnostic intervals seemed not to be associated with poorer survival. Other factors than diagnostic delay should be taken into account to explain this "waiting-time paradox".

α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development.

Background: To optimise care HIV patients need to be promptly initiated on antiretroviral therapy (ART) and subsequently retained on treatment. In this study we report on the interval between enrolment and treatment initiation, and investigate subsequent attrition and mortality of patients on ART at a rural clinic in Malawi., Methods: HIV-positive individuals were recruited to a cohort study between January 2008 and August 2011 at Chilumba Rural Hospital (CRH). Outcomes were ascertained, up to 7 years after enrolment, through follow-up and by linkage to ART registers and the Karonga Health and Demographic Surveillance System (KHDSS). Kaplan-Meier methods and Cox regression were used to examine ART initiation after enrolment, mortality after ART initiation, and attrition after ART initiation., Results: Of the 617 individuals recruited, 523 initiated ART between January 2008 and January 2015. Median time from HIV testing to commencement of ART was 59 days (IQR: 10-330). By a year after enrolment 74.2 % (95 % CI 70.6-77.7 %) had initiated ART. Baseline clinical data at ART initiation and data on attrition was only available for the 438 individuals who initiated ART during active follow-up, between January 2008 and August 2011. Of these individuals, 6 were missing Ministry of Health numbers, leaving 432 included in analyses of attrition and mortality. At 4 years after ART initiation 71.3 % (95 % CI 65.7-76.2 %) of these patients were retained on treatment at the CRH and 17.2 % (95 % CI 13.8-21.4 %) had died. Participants who had a lower CD4 count at enrolment (≤350 cells/μl), enrolled in 2008, or tested for HIV at the CRH rather than through serosurveys, initiated treatment faster. Once on treatment, mortality rates were higher in patients who were HIV tested at the CRH, male, older (≥35 years), missing a CD4 count, or underweight (BMI < 18.5) at ART initiation., Conclusions: Through linkage to the KHDSS and ART registers it was possible to continue follow-up beyond the end of the initial cohort study. Annual mortality after ART initiation remained considerable over a period of 4 years. Greater access to HIV and CD4 testing alongside initiation at higher CD4 counts, as planned in the test and treat strategy, could reduce this mortality.

Background/objectives: Delayed presentation of symptomatic cancer is associated with poorer survival. Aboriginal patients with cancer have higher rates of distant metastases at diagnosis compared with non-Aboriginal Australians. This paper examined factors contributing to delayed diagnosis of cancer among Aboriginal Australians from patient and service providers' perspectives., Methods: In-depth, open-ended interviews were conducted in two stages (2006-2007 and 2011). Inductive thematic analysis was assisted by use of NVivo looking around delays in presentation, diagnosis and referral for cancer., Participants: Aboriginal patients with cancer/family members (n=30) and health service providers (n=62) were recruited from metropolitan Perth and six rural/remote regions of Western Australia., Results: Three broad themes of factors were identified: (1) Contextual factors such as intergenerational impact of colonisation and racism and socioeconomic deprivation have negatively impacted on Aboriginal Australians' trust of the healthcare professionals; (2) health service-related factors included low accessibility to health services, long waiting periods, inadequate numbers of Aboriginal professionals and high staff turnover; (3) patient appraisal of symptoms and decision-making, fear of cancer and denial of symptoms were key reasons patients procrastinated in seeking help. Elements of shame, embarrassment, shyness of seeing the doctor, psychological 'fear of the whole health system', attachment to the land and 'fear of leaving home' for cancer treatment in metropolitan cities were other deterrents for Aboriginal people. Manifestation of masculinity and the belief that 'health is women's domain' emerged as a reason why Aboriginal men were reluctant to receive health checks., Conclusions: Solutions to improved Aboriginal cancer outcomes include focusing on the primary care sector encouraging general practitioners to be proactive to suspicion of symptoms with appropriate investigations to facilitate earlier diagnosis and the need to improve Aboriginal health literacy regarding cancer. Access to health services remains a critical problem affecting timely diagnosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The incidence of rectal cancer in younger patients continues to increase. Because most of these patients do not meet criteria for routine colorectal cancer screening, diagnosis may be delayed, potentially resulting in adverse outcomes. The aim of this study was to determine whether patients under the age of 50 years with rectal cancer have a delay in diagnosis and treatment leading to a worse overall prognosis., Methods: A case control study of patients diagnosed with rectal adenocarcinoma in an academic medical center from 1997 to 2007 under 50 years of age were matched 1:1 to randomly selected patients over the age of 50 years by sex and date of diagnosis. Time to diagnosis, time to treatment, staging of the American Joint Committee on Cancer, and 5-year overall survival were compared., Results: The overall time to treatment from symptom onset was 217 days for patients under the age of 50 years versus 29.5 days if over 50 years of age (P < .0001). The primary delay occurred between the onset of symptoms and presentation to the initial physician. There was no difference in stage at the time of diagnosis or 5-year survival (64% vs 71%, P = .39 and P = .54, respectively)., Conclusions: Patients with rectal cancer under the age of 50 years have symptoms for a considerable period of time before seeking medical care and are referred in less timely manner to specialists. However, the delay in diagnosis did not adversely impact stage on presentation or 5-year survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Strongyloidiasis is one of the most neglected tropical diseases and it exists in Australia. Patients may have acquired their initial infection while in an endemic area. Because of the autoinfective cycle of Strongyloides stercoralis, the causative agent, these patients may remain infected for life unless effectively treated. Corticosteroids have precipitated death in more than 60% of disseminated strongyloidiasis cases., Objective: The aim of this article is to raise awareness of the unique features of S. stercoralis and outline the important role that general practitioners (GPs) have in diagnosing and treating chronic strongyloidiasis, as well as in preventing cases of fatal hyperinfection., Discussion: Chronic strongyloidiasis is not an overt disease - if you don't look for it, you won't find it. In particular, patients who have lived in an endemic area or have unexplained eosinophilia must be checked for the presence of the parasite before initiation of steroid or immunosuppressive therapy. These patients, if infected, may develop hyperinfective syndrome, which has a high fatality rate.

Background: Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy., Objectives: Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities., Design: Retrospective study of all autopsies performed between 2008 and 2014., Setting: Institute of Pathology, Belgrade, Serbia., Subjects and Methods: in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy., Main Outcome Measures: Clinically unrecognized MT., Results: The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death., Conclusion: Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery., Limitations: None.

Delay of the diagnosis of hepatitis C virus (HCV), and its treatment to avert cirrhosis, is often present sincethe early stage of HCV progression is latent. Current methods to determine the incubation time to HCV-related cirrhosis and the duration time from cirrhosis to subsequent events (e.g. complications or death) used to be based on the time of liver biopsy diagnosis and ignore this delay which led to an interval censoring for the first event time and a double censoring for the subsequent event time. To investigate the impact of this delay in estimating HCV progression rates and relevant estimating bias, we present a correlated two-stage progression model for delayed diagnosis time and fit the developed model to the previously studied hepatitis C cohort data from Edinburgh. Our analysis shows that taking the delayed diagnosis into account gives a mildly different estimate of progression rate to cirrhosis and significantly lower estimated progression rate to HCV-related death in comparison with conventional modelling. We also find that when the delay increases, the bias in estimating progression increases significantly., (© The Author(s) 2011.)

Background: Gangrenous cholecystitis (GC) is difficult to diagnose preoperatively in the patient with suspected acute cholecystitis. We sought to characterize preoperative risk factors and post-operative complications., Methods: Pathology reports of all patients undergoing cholecystectomy for suspected acute cholecystitis from June 2010 to January 2014 and admitted through the emergency department were examined. Patients with GC were compared with those with acute/chronic cholecystitis (AC/CC). Data collected included demographics, preoperative signs and symptoms, radiologic studies, operative details, and clinical outcomes., Results: Thirty-eight cases of GC were identified and compared with 171 cases of AC/CC. Compared with AC/CC, GC patients were more likely to be older (57 years vs. 41 years, p < 0.001), of male sex (63% vs. 31%, p < 0.001), hypertensive (47% vs. 22%, p = 0.002), hyperlipidemic (29% vs. 14%, p = 0.026), and diabetic (24% vs. 8%, p = 0.006). GC patients were more likely to have a fever (29% vs. 12%, p = 0.007) and less likely to have nausea/vomiting (61% vs. 80%, p = 0.019) or an impacted gallstone on ultrasound (US) (8% vs. 26%, p = 0.017). Otherwise, there was no significant difference in clinical or US findings. Among GC patients, US findings were absent (8%, n = 3) or minimal (42%, n = 16). Median time from emergency department registration to US (3.3 hours vs. 2.8 hours, p = 0.28) was similar, but US to operation was longer (41.2 hours vs. 18.4 hours, p < 0.001), conversion to open cholecystectomy was more common (37% vs. 10%, p < 0.001), and hospital stay was longer (median, 4 days vs. 2 days, p < 0.0001). Delay in surgical consultation occurred in 16% of GC patients compared with 1% of AC patients (p < 0.001)., Conclusion: Demographic features may be predictive of GC. Absent or minimal US signs occur in 50%, and delay in surgical consultation is common. Postoperative morbidity is greater for patients with GC compared with those with AC/CC., Level of Evidence: Epidemiologic study, level III; therapeutic study, level IV.

Introduction: Visceral leishmaniasis (VL) is among the seven global endemic diseases assigned a high priority by the World Health Organization. In Latin America, most cases occur in Brazil. Despite the availability of intensive treatment resources and protocols for specific treatment, lethality rates for VL have increased in several regions in the country over the past 10 years, particularly in patients under one and over 50 years of age. As the growth of the elderly population accelerates in Brazil, VL poses a greater challenge to public health. Given the scarcity of studies addressing the disease in this age group, the purpose of this study was to identify factors associated with VL lethality among the elderly. METHODS/KEY FINDINGS: This analytical, cross-sectional epidemiological study comprised 80 elderly patients who sought treatment at the teaching hospital of the Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil, in the period 2000-2013.Clinical, laboratory and treatment variables were investigated from records of elderly patients with VL diagnosis confirmed by at least one laboratory test positive (culture for parasite or direct parasitological examination; reactive immunofluorescence; immunochromatographic test with recombinant antigens) or patients without laboratory confirmation who lived in endemic areas and responded favorably to therapeutic trial, as defined by the Brazilian Ministry of Health. Of the 80 patients included, 78 tested positive to at least one exam; in two cases, diagnosis was based on clinical and epidemiological criteria. The lethality rate was 20%. Multivariate analysis revealed an association between death and time elapsed from symptom onset.

The aim of this study was to present a definition of late presentation according to different time periods between initial diagnosis of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) diagnosis which would reliably identify individuals with high risk of mortality within 1 year of diagnosis, and could be used as a suggested common definition.Data of individuals diagnosed from 1994 to February 2012 in Wuhan, China were extracted retrospectively from the national HIV surveillance system. Four time periods (1, 3, 6, and 12 months) combined with the European consensus definition of advanced HIV disease (AHD) were compared. The predictive ability of each definition for identifying an individual who died within 1 year after HIV diagnosis was assessed.A total of 980 patients were included, of whom 289 (29.49%), 324 (33.06%), 353 (36.02%), and 387 (39.49%) were defined as AHD according to the definition of a CD4 count <200 cells/μL or AIDS-defining event (ADE) within 1, 3, 6, and 12 months of HIV diagnosis, respectively. One hundred twenty-seven (12.96%) patients died within 1 year of diagnosis. The highest Youden's index and largest area under the curve were presented in time period within 3 months. Time period within 1 month presented the highest consistency rate, positive likelihood ratio, and kappa value. Longer time periods increased the sensitivity but decreased the specificity.Given the European consensus definitions and the current results, we suggested that AHD could be defined as "a first-reported CD4 count <200 cells/μL or an ADE within 1 month after HIV diagnosis." "Late presentation" could be defined as "a first-reported CD4 count <350 cells/μL or an ADE within 1 month after HIV diagnosis."

Purpose: This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer., Methods: Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors., Results: Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality., Conclusions: Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome., (Copyright © 2015 Elsevier Ltd. All rights reserved.)