Nevin Manimala

Pediatr Hematol Oncol. 2022 Jul 15:1-9. doi: 10.1080/08880018.2022.2079785. Online ahead of print.

ABSTRACT

Risk stratification of pediatric febrile neutropenia (FN) is an established concept, yet clinical risk tools misclassify nearly 5% of clinical standard-risk episodes with severe outcomes. The internal evaluation of a clinical risk tool before implementation has not been well-described. In this noninterventional cohort study, we evaluated a study decision rules (SDR) tool; a clinical risk tool with serial procalcitonin. The study standard-risk (SSR) group met clinical standard-risk criteria with two serial procalcitonin <0.4 ng/mL. The study high-risk (SHR) group met clinical high-risk criteria or clinical standard-risk with a procalcitonin ≥0.4 ng/mL. Descriptive and bivariate statistics compared the groups and outcomes. Clinical criteria alone identified 39.1% (238/608) standard-risk episodes; 5.9% (14/238) had severe events. Prospectively using the SDR, the SHR group encompassed 76.6% (92/120) of episodes; severe events occurred in 20% (3/15) of standard-risk episodes included due to elevated procalcitonin ≥0.4 ng/mL. The SHR group had more blood stream infections [21.7% (20/92) vs. 0% (0/28); P = 0.007] and intensive care admissions [13% (12/92) vs. 3.6% (1/28); P = 0.158]. In conclusion, the SDR with serial procalcitonin aided in identifying severe events in clinical standard-risk episodes, but analysis was limited. Institutions may consider similar internal evaluation methodology before FN episode risk stratification.

PMID:35838022 | DOI:10.1080/08880018.2022.2079785

Pediatr Hematol Oncol. 2022 Jul 15:1-11. doi: 10.1080/08880018.2022.2071510. Online ahead of print.

ABSTRACT

Children with sickle cell anemia (SCA) usually face psychological complications especially depression. Assessment of depression in resource-limited settings may help identify the extent to which the children with SCA in such settings may need its introduction as part of routine care. This study aimed to assess depression in children and adolescents with SCA in a low-resource setting. This cross-sectional observational study involved 84 children and adolescents with SCA aged 7-17 years who were selected using a systematic random sampling technique. Their controls were 84 age- and sex-matched individuals with AA hemoglobin genotype. A structured questionnaire was used to collect socio-demographic data while depression was assessed with the Children’s Depression Inventory. The prevalence of depression was non-significantly higher in subjects compared to the controls (8.3% vs. 2.4%) (Fisher’s χ² = 1.88, p = 0.171). Though not statistically significant, the subjects had 3.7 times higher odds of having depression compared to the controls (OR = 3.7; 95% CI 0.75-18.50; p = 0.107). Of the 5 depression subscales, the subjects had a significantly higher difference in the negative mood (p = 0.042). Despite the comparable prevalence of depression with their normal controls, children and adolescents with SCA had a higher negative mood and higher odds of having depression than normal individuals. Thus, there is a need for the introduction of depression assessment as a complement to routine care of these children with SCA in resource-poor settings.

PMID:35838017 | DOI:10.1080/08880018.2022.2071510

Phys Chem Chem Phys. 2022 Jul 15. doi: 10.1039/d2cp01741e. Online ahead of print.

ABSTRACT

How does a systematic time-dependence of the diffusion coefficient D(t) affect the ergodic and statistical characteristics of fractional Brownian motion (FBM)? Here, we answer this question via studying the characteristics of a set of standard statistical quantifiers relevant to single-particle-tracking (SPT) experiments. We examine, for instance, how the behavior of the ensemble- and time-averaged mean-squared displacements-denoted as the standard MSD 〈x²(Δ)〉 and TAMSD quantifiers-of FBM featuring (where H is the Hurst exponent and Δ is the [lag] time) changes in the presence of a power-law deterministically varying diffusivity D_α(t) ∝ t^α-1-germane to the process of scaled Brownian motion (SBM)-determining the strength of fractional Gaussian noise. The resulting compound “scaled-fractional” Brownian motion or FBM-SBM is found to be nonergodic, with 〈x²(Δ)〉 ∝ Δ^α+2H-1 and . We also detect a stalling behavior of the MSDs for very subdiffusive SBM and FBM, when α + 2H – 1 < 0. The distribution of particle displacements for FBM-SBM remains Gaussian, as that for the parent processes of FBM and SBM, in the entire region of scaling exponents (0 < α < 2 and 0 < H < 1). The FBM-SBM process is aging in a manner similar to SBM. The velocity autocorrelation function (ACF) of particle increments of FBM-SBM exhibits a dip when the parent FBM process is subdiffusive. Both for sub- and superdiffusive FBM contributions to the FBM-SBM process, the SBM exponent affects the long-time decay exponent of the ACF. Applications of the FBM-SBM-amalgamated process to the analysis of SPT data are discussed. A comparative tabulated overview of recent experimental (mainly SPT) and computational datasets amenable for interpretation in terms of FBM-, SBM-, and FBM-SBM-like models of diffusion culminates the presentation. The statistical aspects of the dynamics of a wide range of biological systems is compared in the table, from nanosized beads in living cells, to chromosomal loci, to water diffusion in the brain, and, finally, to patterns of animal movements.

PMID:35838015 | DOI:10.1039/d2cp01741e

Ann Surg. 2022 Jul 15. doi: 10.1097/SLA.0000000000005532. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals.

BACKGROUND: For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for.

METHODS: This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors.

RESULTS: In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex [odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09-1.66], higher body mass index (OR=1.07; 95% CI: 1.05-1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90-3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32-1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55-0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with a C-statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals.

CONCLUSIONS: The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.

PMID:35837978 | DOI:10.1097/SLA.0000000000005532

Ann Surg. 2022 Jul 15. doi: 10.1097/SLA.0000000000005568. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the impact of propofol-based total intravenous anesthesia (TIVA) versus inhalational anesthesia (IA) on the overall survival following cancer surgery.

SUMMARY BACKGROUND DATA: The association between intraoperative anesthetics and patients’ long-term outcomes following cancer surgery remains controversial.

METHODS: This retrospective cohort study used nationwide data from the Korean National Health Insurance Service. Adult patients who underwent cancer resection surgery (breast, gastric, lung, liver, kidney, colorectal, pancreatic, esophageal, and bladder cancer) under general anesthesia between January 2007 and December 2016 were included. Patients were divided into propofol-based TIVA or IA groups according to the type of anesthesia received. A total of 312,985 patients (37,063 in the propofol-based TIVA group and 275,922 patients in the IA group) were eligible for analysis. The primary outcome was the comparison of overall survival following surgery between the groups in each cancer type. We compared the all-cause mortality between the two groups, stratified by cancer type using time-dependent Cox regression after propensity score-based inverse probability of treatment weighting. We further examined the comparison of overall survival in a meta-analysis using data from our study and previously published data comparing propofol-based TIVA with IA after cancer surgery.

RESULTS: The number of deaths in the propofol-based TIVA and IA groups was 5,037 (13.6%) and 45,904 (16.6%), respectively; the median (IQR) follow-up duration was 1192 (637‒2011) days. Multivariable Cox proportional hazards regression analysis revealed no significant association between the type of general anesthesia and overall survival after cancer surgery in the weighted cohort for each cancer type (all P>0.05) and for total population (adjusted hazard ratio: 0.98, 95% CI: 0.93‒1.04). In a meta-analysis, single-center studies showed higher overall survival in the TIVA group than in the IA group (pooled adjusted HR: 0.65, 95% CI: 0.47‒0.91, P=0.01), while multicenter studies showed insignificant pooled adjusted HRs (pooled adjusted HR: 1.05, 95% CI: 0.82‒1.33, P=0.71).

CONCLUSIONS: There is no association between the type of general anesthesia used during cancer surgery and postoperative overall, 1-, and 5-year survival.

PMID:35837948 | DOI:10.1097/SLA.0000000000005568

Ann Surg. 2022 Jul 15. doi: 10.1097/SLA.0000000000005590. Online ahead of print.

ABSTRACT

OBJECTIVE: Test the effectiveness of benchmarked performance reports based on existing discharge data paired with a statewide intervention to implement evidence-based strategies on breast re-excision rates.

SUMMARY BACKGROUND: Breast-conserving surgery (BCS) is a common breast cancer surgery performed in a range of hospital settings. Studies have demonstrated variations in post-BCS re-excision rates, identifying it as a high-value improvement target.

METHODS: Wisconsin Hospital Association discharge data (2017-2019) were used to compare 60-day re-excision rates following BCS for breast cancer. The analysis estimated the difference in the average change pre-to post-intervention between Surgical Collaborative of Wisconsin (SCW) and non-participating hospitals using a logistic mixed-effects model with repeated measures, adjusting for age, payer, and hospital volume, including hospitals as random effects. The intervention included five collaborative meetings in 2018-2019 where surgeon champions shared guideline updates, best practices/challenges, and facilitated action planning. Confidential benchmarked performance reports were provided.

RESULTS: In 2017, there were 3,692 breast procedures in SCW and 1,279 in non-participating hospitals; hospital-level re-excision rates ranged from 5% to >50%. There was no statistically significant baseline difference in re-excision rates between SCW and non-participating hospitals (16.1% vs. 17.1%, P=0.47). Re-excision significantly decreased for SCW but not for non-participating hospitals (OR=0.69, 95%CI=0.52-0.91).

CONCLUSIONS: Benchmarked performance reports and collaborative quality improvement can decrease post-BCS re-excisions, increase quality, and decrease costs. Our study demonstrates the effective use of administrative data as a platform for state-wide quality collaboratives. Using existing data requires fewer resources and offers a new paradigm that promotes participation across practice settings.

PMID:35837946 | DOI:10.1097/SLA.0000000000005590

Lancet Oncol. 2022 Jul;23 Suppl 1:S36. doi: 10.1016/S1470-2045(22)00435-1.

ABSTRACT

BACKGROUND: Cancer is the second leading cause of death in almost all Latin American countries. Knowing where people with cancer die and understanding the factors that affect where they die are public health issues, relevant for the development of policies that ensure the provision of adequate end-of-life care in alignment with patients’ needs and preferences. The objective of this study was to describe and compare the place of death of people with cancer in 12 Latin American countries, and explore associated factors.

METHODS: We conducted a total population observational study using death certificate data from 12 countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Mexico, Paraguay, Peru, and Uruguay). Data from individuals deceased during the most recent full year (Jan 1 to Dec 31) with available data (2016, 2017, or 2018) were included. Place of death was categorised as home, hospital, or other places. The sociodemographic factors, cause of death (10th revision of the International Statistical Classification of Diseases and Related Health Problem cancer codes C00-C97 vs others), and ecological factors were estimated, and a multivariable binary logistic regression analysis with the dependent variable home death versus hospital death was done.

FINDINGS: 3 001 640 deaths were included, of which 491 929 (16·4%) were caused by cancer, ranging from 3161 (8·7%) of 36 441 deaths in El Salvador to 26 027 (33·4%%) of 77 999 deaths in Chile. 1808 (57·2%) of 3161 cancer deaths in El Salvador were in women, a rate that decreased to 3591 (45·5%) of 7884 deaths in Uruguay, but that remained above 50% in half of the included countries (Colombia, Ecuador, El Salvador, Guatemala, Mexico, and Peru). In all countries, 199 900 (40·7%) of 491 574 patients with cancer died before the age of 64 years. Between 32 513 (14·9%) of 217 697 (in Brazil) and 6216 (80·3%) of 7738 (in Guatemala) cancer deaths occurred at home; whereas 175 464 (80·6%) of 217 697 (in Brazil) and 1033 (13·3%) of 7738 (in Guatemala) cancer deaths occurred in hospital. The odds ratios for death at home for people with cancer aged 50-79 years was 1·6 (95% CI 1·6-1·7; p<0·001) and 3·0 (2·9-3·0; p<0·001) for people aged 80 years and older, comparing with those younger than 50 years.

INTERPRETATION: Factors affecting place of death patterns in Latin America are country-specific. A high percentage of people dying at home does not necessarily suggest a good palliative care provision, especially in countries with poor palliative care programmes. The health facilities available in each country might explain the variations in the number of places where people die. These findings show current needs and can help to guide different policies to improve end-of-life care for patients with cancer.

FUNDING: None.

PMID:35837933 | DOI:10.1016/S1470-2045(22)00435-1

Lancet Oncol. 2022 Jul;23 Suppl 1:S35. doi: 10.1016/S1470-2045(22)00434-X.

ABSTRACT

BACKGROUND: Oral cancer is one of the most common types of cancer in the world, leading to over 177 000 deaths worldwide annually. The literature suggests that oral cancer might be preceded by potentially malignant oral lesions, such as oral lichen planus, a multifactorial chronic inflammatory condition with an autoimmune component. Smoking and alcohol consumption are two of the many triggers of oral lichen planus and oral cancer. Both habits have likewise been associated with the Thr102Cys polymorphisms in the HTR2A gene, which codes the 5-hydroxytryptamine receptor 2A (5-HT-2A). The aim of this study was to investigate the Thr102Cys polymorphism rs6313 (NG_013011.1:g.6230C>T on GenBank) in the HTR2A gene in patients with oral lichen planus, and to explore its association with smoking and alcohol consumption.

METHODS: This case-control study took place in 2009-16 in the Centre of Diagnosis of Oral Diseases of the Federal University of Pelotas, Brazil, a national reference centre in histopathological diagnosis. Women aged 18 years or older with a histopathological diagnosis of oral lichen planus and healthy controls aged 18 years or older were included. Each group included patients with and without smoking or alcohol consumption habits. Men and patients with other conditions were excluded. Cell samples from oral lesions were collected with cytological brushes (QIAamp DNA FFPE Tissue Kit, Qiagen, Hilden, Germany) for DNA extraction, and the Thr102Cys polymorphism was genotyped using 40x Human Custom TaqMan Genotyping Assay primers and probes (Life Technologies, Foster City, CA, USA). The study was approved by the Research Ethics Committee of the Federal University of Pelotas (reference 058/2008) and written consent was obtained from all participants. Statistical analyses were done with the Statistical Package for Social Sciences version 16.0. Categorical variables were analysed with the Chi-square test. Logistic regression analysis was presented by odds ratios (OR) and 95% CIs to evaluate the risk of Thr102Cys single nucleotide polymorphism in patients with oral lichen planus.

FINDINGS: 108 individuals were included (46 cases and 62 controls). Median age was 58 years (IQR 51-68). Significant differences were noted between patients in the control and oral lichen planus groups: smoking habits (p<0·0001), alcohol consumption (p=0·035), and presence of the Thr allele (p=0·021) were all higher in the control group. The adjusted logistic regression analysis showed that smokers had a reduced risk (OR 0·18 [95% CI 0·05-0·60]; p=0·005) of developing oral lichen planus compared with non-smokers. Moreover, individuals carrying the Thr allele in the Thr102Cys polymorphism also had a reduced risk (0·19 [0·05-0·67]; p=0·010) of developing oral lichen planus.

INTERPRETATION: Our results show that oral lichen planus is associated with the presence or absence of the Thr102Cys polymorphism and smoking habits. Although tobacco is a known carcinogen, the presence of the Thr allele in smokers might offer a protective effect to oral lichen planus development. Serotonin induces signalling cascades and platelet aggregation via 5-HT-2A, so even slight mutations might modify the receptor’s function. Also, studies suggest that tobacco could alter and suppress immunological mechanisms. Considering the sample median age and that aging also affects immunity function, it is possible that mutations on 5-HT-2A receptors along with the tobacco immunosuppression might be beneficial in preventing immune-mediated disorders such as oral lichen planus. Nevertheless, it is noteworthy that the adverse effects of smoking far outweigh any benefits shown by this association.

FUNDING: None.

PMID:35837932 | DOI:10.1016/S1470-2045(22)00434-X

Lancet Oncol. 2022 Jul;23 Suppl 1:S33. doi: 10.1016/S1470-2045(22)00432-6.

ABSTRACT

BACKGROUND: Colorectal cancer is the third most frequent malignant disease worldwide. In Chile, colorectal cancer has been part of the Garantías Explícitas en Salud (Explicit Guarantees in Health Programme; also known as GES), which aims to ensure prompt access to affordable and quality health care, since 2014. Survival depends on the diagnosis of the disease in the earliest possible stage and on rapid access to adequate treatment. However, extreme inequality in social factors, such as education and income, has resulted in poor outcomes in cancer survival. The aim of this study was to obtain data on the epidemiology of colorectal cancer in Chile (in 2009-18) and on the effect of measurable factors on survival.

METHODS: Publicly available data corresponding to the period of 2009-18 were obtained from registries of mortality and hospital discharges published by the Chilean Health Ministry and National Institute of Statistics, allowing for follow-up of individuals. Individual survival was studied by Kaplan-Meier curves. A Cox proportional-hazards model was used to estimate the effect of the measurable factors.

FINDINGS: 103 239 hospital discharges of 41 615 patients with colorectal cancer were recorded in Chile in 2009-18. 24 217 (65·9%) patients died of the disease. By analysing empirical Kaplan-Meier survival rates, we observed a 5-year survival rate of 43·2% (95% CI 42·7-43·8), considering all patients in the treatment database, with no significant differences observed between men and women. A significant survival difference was observed between patients treated in public (5-year survival: 39·1% (38·5-39·7) and private (5-year survival: 63·4 % (61·9-64·9) health insurance systems (p<0·0001). We also observed differences within the public health insurance subgroups, showing poorer outcomes with decreased socioeconomic conditions (5-year survival rates ranging from 46·7% [45·2-48·3] in the wealthiest group to 30·9% [29·6-32·2] in the poorest group; p<0·0001). Higher survival rates were also seen in patients treated in Santiago, the capital, than in patients treated in other regions in the country. Survival rates did not improve since the implementation of GES (hazard ratio 0·99 [95% CI 0·94-1·05]; p=0·81).

INTERPRETATION: We found an overall 5-year survival rate of 43·2% and a significant difference between health insurance status, with patients with private health insurance reaching survival curves similar to those observed in high-income countries. Barriers to health access, affected by a centralised distribution of resources, with higher availability of resources, such as specialty physicians and colonoscopy, in private hospitals, can be affecting factors. Although GES was created to ensure transversal access to diagnosis and treatment of colorectal cancer, no effect of the programme was found. It is yet to be determined whether results regarding colorectal cancer are not visible because 5 years are not enough to assess the effect of GES, or whether early diagnosis for colorectal cancer is the dominant factor, which can only be managed with screening programmes that are not included in GES.

FUNDING: Complex Engineering Systems Institute (Centro Basal ANID/AFB18003) and Agencia Nacional de Investigación y Desarrollo/Programa de Becas/Doctorado Nacional 21200869.

PMID:35837930 | DOI:10.1016/S1470-2045(22)00432-6

Lancet Oncol. 2022 Jul;23 Suppl 1:S28. doi: 10.1016/S1470-2045(22)00427-2.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had a direct effect on patients with cancer, as reflected by the large number of COVID-19-related cancer deaths reported worldwide and the substantial decrease in cancer-related consultations during the pandemic. However, the impact of the COVID-19 pandemic on cancer mortality in Latin American countries has not been properly estimated. The aim of this study was to analyse the excess mortality related to cancer during the pandemic in Peru, including deaths directly or indirectly attributed to COVID-19.

METHODS: Excess mortality, which compares the number of deaths by any cause with the average number of expected deaths in typical circumstances during a specific timeframe, can be used as a simple but reliable indicator of the impact of the COVID-19 pandemic on cancer services. We carried out a descriptive study using data from the Peruvian death registration system, from which we filtered records that had registered neoplastic diseases (according to the tenth revision of WHO’s International Statistical Classification of Diseases and Related Health Problems) as the cause of death between. Only data for the period of March 15 to June 30 in the years 2017-20 was included. We calculated excess mortality by subtracting the average number of deaths recorded for the indicated period between 2017 and 2019 from the same period of 2020 records (ie, the duration of lockdown measures in Peru) to obtain the percentage of excess mortality.

FINDINGS: The percentage of changes in the number of cancer-related deaths in Peru was +13·90% from 2017 to 2018, -1·27% from 2018 to 2019, and +16·94% from 2019 to 2020. We found an excess mortality of 928 cases (corresponding to an excess mortality of +17·27%) among patients with cancer, when comparing years 2017-19 with the year 2020. During the lockdown in 2020, 3135 (58·4%) of 5372 cancer deaths happened at home (vs 5900 [44·2%] of 13 338 for the years 2017-19). The highest excess mortality percentage was observed in patients with prostate cancer (+50·43%), breast cancer (+33·62%), and leukaemia (32·78%). Although these findings appear to be in line with reports from other countries, only 184 (3·4%) of 5372 deaths were registered with COVID-19 as an additional cause of death.

INTERPRETATION: Our results suggest that COVID-19 control measures (eg, lockdowns, physical distancing, and isolation of symptomatic patients), alongside the overwhelming strain on the health-care system, had a detrimental impact on cancer mortality in Peru. The pandemic has exposed flaws in the Peruvian health-care system, especially regarding cancer care. Although we recognise that the rate of COVID-19 testing in Peru is one of the lowest in Latin America, the excess of cancer deaths cannot be fully explained by COVID-19. These findings might be an indication that the alarming increase in cancer mortality in Peru could continue over the upcoming months if no action is taken. Our study also shows the importance of an adequate registry of deaths. We recommend that the national authorities should implement policies to limit the impact of the COVID-19 pandemic on patients with cancer, and that the continuous update and monitoring of deaths initiated during the COVID-19 pandemic is sustained. These measures can help to confirm the increasing trend in cancer deaths; serve as a rationale to develop strategies that can alleviate this burden (eg, by adopting models for delivering optimal cancer care while minimising transmission of COVID-19); and minimise the possibility of an increase in patients presenting with advanced-stage cancers.

FUNDING: International Joint Laboratories Programme of the French National Research Institute for Sustainable Development.

PMID:35837924 | DOI:10.1016/S1470-2045(22)00427-2