Category: Statistics

Cancer. 2021 Apr 27. doi: 10.1002/cncr.33515. Online ahead of print.

ABSTRACT

BACKGROUND: Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras.

METHODS: The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged ≥67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars.

RESULTS: Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients.

CONCLUSIONS: The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

PMID:33905529 | DOI:10.1002/cncr.33515

Mol Biol Evol. 2021 Apr 27:msab119. doi: 10.1093/molbev/msab119. Online ahead of print.

ABSTRACT

Convergent phenotypic evolution provides some of the strongest evidence for adaptation. However, the extent to which recurrent phenotypic adaptation has arisen via parallelism at the molecular level remains unresolved, as does the evolutionary origin of alleles underlying such adaptation. Here, we investigate genetic mechanisms of convergent highland adaptation in maize landrace populations and evaluate the genetic sources of recurrently selected alleles. Population branch excess statistics reveal substantial evidence of parallel adaptation at the level of individual SNPs, genes and pathways in four independent highland maize populations. The majority of convergently selected SNPs originated via migration from a single population, most likely in the Mesoamerican highlands, while standing variation introduced by ancient gene flow was also a contributor. Polygenic adaptation analyses of quantitative traits reveal that alleles affecting flowering time are significantly associated with elevation, indicating the flowering time pathway was targeted by highland adaptation. In addition, repeatedly selected genes were significantly enriched in the flowering time pathway, indicating their significance in adapting to highland conditions. Overall, our study system represents a promising model to study convergent evolution in plants with potential applications to crop adaptation across environmental gradients. Keyword: convergent adaptation, flowering time, polygenic adaptation, population branch statistic.

PMID:33905497 | DOI:10.1093/molbev/msab119

G3 (Bethesda). 2021 Apr 26:jkab133. doi: 10.1093/g3journal/jkab133. Online ahead of print.

ABSTRACT

This work represents a novel mechanistic approach to simulate and study genomic networks with accompanying regulatory interactions and complex mechanisms of quantitative trait formation. The approach implemented in MeSCoT software is conceptually based on the omnigenic genetic model of quantitative (complex) trait, and closely imitates the basic in vivo mechanisms of quantitative trait realization. The software provides a framework to study molecular mechanisms of gene-by-gene and gene-by-environment interactions underlying quantitative trait’s realization and allows detailed mechanistic studies of impact of genetic and phenotypic variance on gene regulation. MeSCoT performs a detailed simulation of genes’ regulatory interactions for variable genomic architectures, and generates complete set of transcriptional and translational data together with simulated quantitative trait values. Such data provide opportunities to study, for example, verification of novel statistical methods aiming to integrate intermediate phenotypes together with final phenotype in quantitative genetic analyses, or to investigate novel approaches for exploiting gene-by-gene and gene-by-environment interactions.

PMID:33905502 | DOI:10.1093/g3journal/jkab133

Clin Infect Dis. 2021 Apr 27:ciab192. doi: 10.1093/cid/ciab192. Online ahead of print.

ABSTRACT

Maps of the geographical variation in prevalence play an important role in large-scale programmes for the control of Neglected Tropical Diseases. Pre-control mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed post-intervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by two kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest; digital images of environmental factors that are predictive of local prevalence. In this paper, we focus on the design and analysis of impact surveys, i.e. prevalence surveys that are conducted post-intervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analysed as efficiently as possible so as to make best use of hard-won field data. We use three case-studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organisation guidelines. In all three cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other Neglected Tropical Diseases.

PMID:33905476 | DOI:10.1093/cid/ciab192

Clin Infect Dis. 2021 Apr 27:ciab190. doi: 10.1093/cid/ciab190. Online ahead of print.

ABSTRACT

BACKGROUND: The gambiense human African trypanosomiasis (gHAT) elimination programme in the Democratic Republic of Congo (DRC) routinely collects case data through passive surveillance and active screening, with several regions reporting no cases for several years, despite being endemic in the early 2000s.

METHODS: We use mathematical models fitted to longitudinal data to estimate the probability that selected administrative regions have already achieved elimination of transmission (EOT) of gHAT. We examine the impact of active screening coverage on the certainty of model estimates for transmission and therefore the role of screening in the measurement of EOT.

RESULTS: In three example health zones of Sud-Ubangi province we find there is a moderate (>40%) probability that EOT has been achieved by 2018, based on 2000-2016 data. Budjala and Mbaya reported zero cases during 2017-18 and this further increases our respective estimates to 99.9% and 99.6% (Model S); and to 87.3% and 92.1% (Model W). Bominenge had recent case reporting, however if zero cases were found in 2021 it would substantially raise our certainty that EOT has been met there (99.0% for Model S and 88.5% for Model W), and this could be higher with 50% coverage screening that year (99.1% for Model S and 94.0% for Model W).

CONCLUSIONS: We demonstrate how routine surveillance data coupled with mechanistic modelling can estimate the likelihood that EOT has already been achieved. Such quantitative assessment will become increasingly important for measuring local achievement of EOT as 2030 approaches.

PMID:33905480 | DOI:10.1093/cid/ciab190

Clin Infect Dis. 2021 Apr 27:ciab370. doi: 10.1093/cid/ciab370. Online ahead of print.

ABSTRACT

BACKGROUND: Lyme neuroborreliosis peripheral facial palsy (LNB PFP) and idiopathic peripheral facial palsy, Bell’s palsy (BP), are the most common causes of facial palsy in borrelia-endemic areas and are clinically similar. Early treatment with corticosteroids has been shown to be effective in Bell’s palsy and antibiotics improve outcome in LNB, but there is a lack of knowledge on how the addition of corticosteroids to standard antibiotic treatment affects outcome in LNB PFP.

METHODS: This prospective open trial with historical controls was conducted at two large hospitals in western Sweden between 2011 and 2018. Adults presenting with LNB PFP were included in the study group and were treated with oral doxycycline 200 mg b.i.d. for 10 days and prednisolone 60 mg o.d. for 5 days, then tapered over 5 days. The historical controls were adult patients with LNB PFP included in previous studies and treated with oral doxycycline. Both groups underwent a follow-up lumbar puncture and were followed until complete recovery or for 12 months.

RESULTS: Fifty-seven patients were included, 27 in the study group and 30 in the control group. Two patients (6%) in the study group and 6 patients (20%) in the control group suffered from sequelae at end follow up. There was no statistically significant difference between the groups, neither in the proportion of patients with sequelae, nor in the decline in CSF mononuclear cell count.

CONCLUSIONS: Adjunctive corticosteroids neither improve nor impair the outcome for patients with Lyme neuroborreliosis peripheral facial palsy treated with doxycycline.

PMID:33905494 | DOI:10.1093/cid/ciab370

PLoS One. 2021 Apr 27;16(4):e0250637. doi: 10.1371/journal.pone.0250637. eCollection 2021.

ABSTRACT

INTRODUCTION: Pregnant women who disclose their HIV-positive status to their sexual partners have played an important role in reducing the risk of HIV/AIDS transmission to the baby during the antepartum, intrapartum, and postnatal periods. Studies are limited in the current study area in a similar arena. Therefore, this study aimed to assess the proportion of HIV-positive status disclosure and its associated factors among pregnant women.

METHODS: A facility-based cross-sectional study was conducted among 156 HIV-positive pregnant women in Dire Dawa administrative from March 12th to May 10th, 2020. Data were generated using a pretested structured questionnaire through face-to-face interviews. Binary logistic regression analysis was employed to identify the predictor variables associated with the disclosure of HIV-positive status among pregnant women to their sexual partners. Finally, the adjusted odds ratio with 95% confidence intervals at P-value< 0.05 was considered statistically significant.

RESULTS: Of the total, 135 (86.5%) of HIV-positive pregnant women disclosed their HIV status to their sexual partner. Christian followers (both Orthodox and Protestant) [AOR = 8.8, 95% CI: 2.3. 34] more likely to disclose HIV status to their sexual partner than those Muslims. Those participants who started practicing safer sex [AOR = 17.6, 95% CI: 4-77] and those women who had a smooth relationship before the HIV disclosure were [AOR = 14.7, 95% CI: 3-68.6] more likely to disclose HIV status to their sexual partner than their counterparts, respectively.

CONCLUSIONS: The proportion of HIV serostatus disclosure by HIV-positive pregnant women attending antenatal care services to their sexual partners was encouraging. However, this does not mean that there is no need for further awareness and intervention. Hence, interventions to boost and support women in safely disclosing their HIV-positive status are needed.

PMID:33905432 | DOI:10.1371/journal.pone.0250637

PLoS Pathog. 2021 Apr 27;17(4):e1009536. doi: 10.1371/journal.ppat.1009536. Online ahead of print.

ABSTRACT

Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived DCs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal DCs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.

PMID:33905459 | DOI:10.1371/journal.ppat.1009536

PLoS Med. 2021 Apr 27;18(4):e1003611. doi: 10.1371/journal.pmed.1003611. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.

METHODS AND FINDINGS: Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery. We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m2. Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks’ gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19+5 weeks’ gestation, a change of -0·6 (95% CI -0.8 to -0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks’ gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study’s main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.

CONCLUSIONS: Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.

PMID:33905424 | DOI:10.1371/journal.pmed.1003611

PLoS One. 2021 Apr 27;16(4):e0249992. doi: 10.1371/journal.pone.0249992. eCollection 2021.

ABSTRACT

BACKGROUND: Viruses are responsible for a large proportion of acute respiratory tract infections (ARTIs). Human influenza, parainfluenza, respiratory-syncytial-virus, and adenoviruses are among the leading cause of ARTIs. Epidemiological evidence of those respiratory viruses is limited in the East Africa Community (EAC) region. This review sought to identify the prevalence of respiratory syncytial virus, parainfluenza, and adenoviruses among cases of ARTI in the EAC from 2007 to 2020.

METHODS: A literature search was conducted in Medline, Global Index Medicus, and the grey literature from public health institutions and programs in the EAC. Two independent reviewers performed data extraction. We used a random effects model to pool the prevalence estimate across studies. We assessed heterogeneity with the I2 statistic, and Cochran’s Q test, and further we did subgroup analysis. This review was registered with PROSPERO under registration number CRD42018110186.

RESULTS: A total of 12 studies met the eligibility criteria for the studies documented from 2007 to 2020. The overall pooled prevalence of adenoviruses was 13% (95% confidence interval [CI]: 6-21, N = 28829), respiratory syncytial virus 11% (95% CI: 7-15, N = 22627), and parainfluenza was 9% (95% CI: 7-11, N = 28363). Pooled prevalence of reported ARTIs, all ages, and locality varied in the included studies. Studies among participants with severe acute respiratory disease had a higher pooled prevalence of all the three viruses. Considerable heterogeneity was noted overall and in subgroup analysis.

CONCLUSION: Our findings indicate that human adenoviruses, respiratory syncytial virus and parainfluenza virus are prevalent in Kenya, Tanzania, and Uganda. These three respiratory viruses contribute substantially to ARTIs in the EAC, particularly among those with severe disease and those aged five and above.

PMID:33905425 | DOI:10.1371/journal.pone.0249992