Prevalence of locoregional recurrence and survival post-treatment of head and neck cancers in Africa: a systematic review and meta-analysis.

Background: Recurrent cancers of the head and neck are associated with poor survival outcome. Yet, their burden in Africa is not reliably known. We therefore aimed to estimate the prevalence of recurrence and the 5-year overall survival among patients treated for head and neck cancers (HNC) in Africa. Method: In this systematic review and meta-analysis, we searched four electronic databases (Pubmed, CINAHL, MEDLINE, and Web of Science) and the grey literature for studies reporting the prevalence of HNC recurrence and 5-year overall survival post treatment, published between January 1, 2002, and December 31, 2022. We contacted corresponding authors of relevant studies. Searches were extended to reference lists of review articles and other relevant sources for potentially eligible studies. Each record was assessed for inclusion or exclusion by two independent reviewers. Records with individual-level data on recurrence and survival conducted in Africa were included while exclusion was based on the study design and availability of relevant data. Data were independently extracted by three reviewers from eligible studies, and summary estimates were sought. Our primary outcomes were recurrence and 5-year overall survival of patients who have been treated for HNC, and our secondary outcomes included risk factors, tumor site, squamous cell histology, clinical stage of tumor, and treatment options received. Only records selected for primary outcomes were assessed for secondary outcome data extraction. Random-effects meta-analysis was conducted for each outcome. Meta-regression models were used in addressing sample heterogeneity among the studies. Protocol for this study was registered with PROSPERO, CRD42022372307. Findings: This systematic review and meta-analysis returned 3998 records, yielding 28 included studies after exclusion. Eighteen studies reported on the prevalence of HNC recurrence while 24 articles reported on the 5-year overall survival. Of the pooled total study population, 7199 (70.5%) of 10,218 patients were males while 2603 (25.5%) were females. We found that the prevalence of HNC recurrence was 15.4% (I2 = 96.2%; 95% CI: 9.5-22.3; n = 3214; k = 18), and the 5-year overall survival was 54.4% (I2 = 99.5%; 95% CI: 40.1-68.4; n = 9798; k = 24). We also found that the prevalence of smoking and alcohol consumption as risk factors for HNC were 42.6% (I2 = 98.8%; 95% CI: 25.2-61.0; n = 4374; k = 15) and 35.8% (I2 = 98.9%; 95% CI: 21.7-51.4; n = 4110; k = 11) respectively. The pooled current prevalence for advanced HNC (clinical stages III-IV) was 80.0% (I2 = 99.2%; 95% CI: 68.6-89.5; n = 7624; k = 18) compared to 12.2% (I2 = 96.4%; 95% CI: 6.2-19.8; n = 7624; k = 18) in early disease (clinical stages I-II). Interpretation: The results showed significantly high prevalence of cancer recurrence, poor 5-year overall survival and very high prevalence of advanced cancers at time of diagnosis. This study provides robust evidence for strategies towards prompt diagnosis and appropriate management of HNC to improve patients' outcome in the African continent. Funding: This study was not supported by any funding.

Older people's preferences for self-involvement in decision-making if faced with serious illness / As preferências de pessoas idosas pelo autoenvolvimento na tomada de decisão numa situação de doença grave

OBJECTIVES: To examine older people's preferences for self-involvement in end-of-life care decision-making in scenarios of mental capacity (competency) and incapacity, and to identify associated factors. METHODS: A cross-sectional survey was conducted including 400 individuals aged 60+ years living in the city of Belo Horizonte, Brazil. RESULTS: Among 400 respondents, 95.3% preferred self-involvement when capable (due to the high percentage, associated factors were not calculated) and 64.5% preferred self-involvement when incapable through, for example, a living will. Considering that participants could choose multiple answers, the most frequent combinations in the capacity scenario were "yourself" and "other relatives" (76.8%) and "yourself" and "the doctor" (67.8%). In the incapacity scenario, the most frequent combinations were "yourself" and "other relatives" (usually their " children and, less often, their grandchildren) (59.3%) and "yourself" and "the doctor" (48.5%). Three factors were associated with a preference for self-involvement in an incapacity scenario. Those who were married or had a partner (widowed; adjusted odds ratio [AOR] = 0.37; 95% confidence interval [CI] 0.19-0.68) and those who were male (female; AOR = 0.62; 95%CI 0.38-1.00) were less likely to prefer self-involvement. Those who were younger, as in age bands 60-69 years (80+; AOR = 2.35; 95%CI 1.20-4.58) and 70-79 years (80+; AOR = 2.45; 95%CI 1.21-4.94), were more likely to prefer self-involvement. CONCLUSIONS: Most participants preferred self-involvement in both scenarios of capacity and incapacity. Preference for self-involvement was higher in the scenario of capacity, while preference for the involvement of other relatives (usually their children) was greater in the scenario of incapacity.

OBJETIVOS: O objetivo deste estudo foi examinar as preferências de pessoas idosas pelo autoenvolvimento na tomada de decisões nos cuidados de saúde em fim de vida em cenários de capacidade e incapacidade mental (competência), e identificar os fatores associados. METODOLOGIA: Foi realizado um estudo transversal, com 400 indivíduos, com idade 60 anos ou mais, residentes na cidade de Belo Horizonte, Brasil. RESULTADOS: Entre os 400 entrevistados, 95,3% preferiram o autoenvolvimento, quando capazes, na tomada de decisões (devido ao alt percentual, fatores associados não foram caculados); e 64,5% preferiram o autoenvolvimento, quando incapazes de tomar decisões, por meio, por exemplo, de um testamento em vida. Considerando que os participantes puderam escolher mais de uma resposta, as combinações mais frequentes para o cenário de capacidade foram: participantes e outros familiares (76,8%); e participantes e médicos (67,8%). No cenário de incapacidade, as combinações mais frequentes foram: participantes e outros familiares (geralmente filhos e netos) (59,3%); e participantes e médicos (48,5%). Três fatores foram associados à preferência pelo i-r autoenvolvimento em um cenário de incapacidade. Aqueles que eram casados ou com companheiro (viúvo; odds ratio ajustada (AOR) = 0,37; intervalo de confiança (IC) 95% 0,19-0,68) e os homens (mulheres; AOR = 0,62; IC95% 0,38-1,00) foram menos propensos a preferir o autoenvolvimento. Os mais jovens: 60-69 anos (80+; AOR = 2,35; IC95% 1,20-4,58) and 70-79 anos (80+; AOR = 2,45; IC95% 1,214,94) foram mais prováveis de preferir o autoenvolvimento. CONCLUSÕES: A maioria dos participantes preferiu o autoenvolvimento em ambos os cenários de capacidade e incapacidade. A preferência pelo autoenvolvimento foi maior no cenário de capacidade, enquanto a preferência pelo envolvimento de outros familiares (geralmente filhos) foi maior no cenário de incapacidade.

Preference for death at home and associated factors among older people in the city of Belo Horizonte, Brazil.

We examined people's preferences for place of death and identified factors associated with a home death preference. We asked a representative sample (N = 400) of older people (≥ 60 years) residents in the city of Belo Horizonte, about their preferences for place of death in a situation of serious illness with less than a year to live. Data were analyzed using binomial regression to identify associated factors. 52.2% indicate home as the preferred place of death. Five variables were associated with preference for death at home: those living with 1 child (odds ratio (OR)0.41; 95% confidence interval (CI):0.18-0.92; ref: without children); being in education for up to 4 years (OR0.42; 95% CI:0.20-0.89; ref: higher education); finding it difficult to live with the present income (OR3.18; 95% CI:1.53-6.62; ref: living comfortably); self-assessed fair overall health (OR2.07; 95% CI:1.06-4.03; ref: very good health) and selecting "choosing who makes decisions about your care" as the care priority that would matter to them the most (OR2.43; 95%CI:1.34-4.40; ref: dying in the place you want). Most respondents chose home as preferred place of death. However, most residents of Belo Horizonte die in hospitals, suggesting that preferences are not being considered.

Preference for death at home and associated factors among older people in the city of Belo Horizonte, Brazil / Preferência por morrer em casa e fatores associados de pessoas idosas da cidade de Belo Horizonte, Brasil

Abstract We examined people's preferences for place of death and identified factors associated with a home death preference. We asked a representative sample (N = 400) of older people (≥ 60 years) residents in the city of Belo Horizonte, about their preferences for place of death in a situation of serious illness with less than a year to live. Data were analyzed using binomial regression to identify associated factors. 52.2% indicate home as the preferred place of death. Five variables were associated with preference for death at home: those living with 1 child (odds ratio (OR)0.41; 95% confidence interval (CI):0.18-0.92; ref: without children); being in education for up to 4 years (OR0.42; 95% CI:0.20-0.89; ref: higher education); finding it difficult to live with the present income (OR3.18; 95% CI:1.53-6.62; ref: living comfortably); self-assessed fair overall health (OR2.07; 95% CI:1.06-4.03; ref: very good health) and selecting "choosing who makes decisions about your care" as the care priority that would matter to them the most (OR2.43; 95%CI:1.34-4.40; ref: dying in the place you want). Most respondents chose home as preferred place of death. However, most residents of Belo Horizonte die in hospitals, suggesting that preferences are not being considered.

Resumo Examinamos as preferências das pessoas para o local da morte e identificamos os fatores associados com a preferência pela morte em casa. Perguntamos para uma amostra representativa (N = 400) de pessoas idosas (≥ 60 anos) residentes da cidade de Belo Horizonte, sobre suas preferências pelo local da morte numa situação de doença grave, com menos de um ano de vida. Os dados foram analisados utilizando regressão binomial para identificar os fatores associados. Indicaram a casa como o local preferido de morte, 52,2%. Cinco variáveis foram associadas à preferência por morte em casa: aqueles que vivem com 1 criança (odds ratio(OR)0,41; intervalo de confiança (CI)95%:0,18-0,92; ref: nenhuma criança); ter até 4 anos de escolaridade (OR0,42; CI95%:0,20-0,89; ref: ensino superior); ser difícil viver com o rendimento atual (OR3,18; CI95%:1,53-6,62; ref: vive confortavelmente); avaliar a sua saúde geral como razoável (OR2,07; CI95%:1,06-4,03; ref: saúde muito boa) e selecionar "escolher quem toma decisões sobre os cuidados" como a prioridade de cuidado mais importante (OR2,43; CI95%:1,34-4,40; ref: morrer no local que se quer). A maioria dos entrevistados expressaram preferência por morrer em casa. No entanto, a maioria dos residentes de Belo Horizonte morre nos hospitais, sugerindo que as preferências não estão sendo consideradas.

Permutations of functional magnetic resonance imaging classification may not be normally distributed.

A fundamental question that often occurs in statistical tests is the normality of distributions. Countless distributions exist in science and life, but one distribution that is obtained via permutations, usually referred to as permutation distribution, is interesting. Although a permutation distribution should behave in accord with the central limit theorem, if both the independence condition and the identical distribution condition are fulfilled, no studies have corroborated this concurrence in functional magnetic resonance imaging data. In this work, we used Anderson-Darling test to evaluate the accordance level of permutation distributions of classification accuracies to normality expected under central limit theorem. A simulation study has been carried out using functional magnetic resonance imaging data collected, while human subjects responded to visual stimulation paradigms. Two scrambling schemes are evaluated: the first based on permuting both the training and the testing sets and the second on permuting only the testing set. The results showed that, while a normal distribution does not adequately fit to permutation distributions most of the times, it tends to be quite well acceptable when mean classification accuracies averaged over a set of different classifiers is considered. The results also showed that permutation distributions can be probabilistically affected by performing motion correction to functional magnetic resonance imaging data, and thus may weaken the approximation of permutation distributions to a normal law. Such findings, however, have no relation to univariate/univoxel analysis of functional magnetic resonance imaging data. Overall, the results revealed a strong dependence across the folds of cross-validation and across functional magnetic resonance imaging runs and that may hinder the reliability of using cross-validation. The obtained p-values and the drawn confidence level intervals exhibited beyond doubt that different permutation schemes may beget different permutation distributions as well as different levels of accord with central limit theorem. We also found that different permutation schemes can lead to different permutation distributions and that may lead to different assessment of the statistical significance of classification accuracy.

Effects of the menstrual cycle and oral contraception on singers' pitch control.

PURPOSE: Difficulties with intonation and vibrato control during the menstrual cycle have been reported by singers; however, this phenomenon has not yet been systematically investigated. METHOD: A double-blind randomized placebo-controlled trial assessing effects of the menstrual cycle and use of a combined oral contraceptive pill (OCP) on pitch control in singing is presented. Audio-electrolaryngograph recordings were made and blood samples were taken from 9 singers in each of the 3 phases of the menstrual cycle both under the placebo and the OCP conditions for a total of 6 months. Participants sang an exercise consisting of an ascending octave followed by a descending major triad, starting on pitches F4 and B4. Pitch control was assessed in terms of the octave's deviations from pure intonation and of the vibrato rate and extent. RESULTS: Significant differences were found between the 3 phases of the cycle regarding octave size only for pitch F5 during OCP use. Significant vibrato rate differences between placebo and OCP conditions were found only for pitch F5. CONCLUSION: OCP use may have an effect on pitch control in singers. Possible explanations point to a complex interaction between hormonal milieu and pitch control, enhancing the need for longitudinal studies.

Species-specific codon context rules unveil non-neutrality effects of synonymous mutations.

BACKGROUND: Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution. METHODOLOGIES/PRINCIPAL FINDINGS: Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases. CONCLUSIONS: Since in vivo studies provide evidence for a role of codon context on decoding fidelity in E. coli and for decoding efficiency in mammalian cells, our data support the hypothesis that, like codon usage, codon context modulates the evolution of gene primary structure and fine tunes the structure of open reading frames for high genome translational fidelity and efficiency in the 3 domains of life.

Computational and statistical methodologies for ORFeome primary structure analysis.

Codon usage and context are biased in open reading frames (ORFs) of most genomes. Codon usage is largely influenced by biased genome G+C pressure, in particular in prokaryotes, but the general rules that govern the evolution of codon context remain largely elusive. To shed new light into this question, we have developed computational, statistical, and graphical tools for analysis of codon context on an ORFeome wide scale. Here, we describe these methodologies in detail and show how they can be used for analysis of ORFs of any genome sequenced.

Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure.

BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

Comparative context analysis of codon pairs on an ORFeome scale.

Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context.