Nevin Manimala

PLoS One. 2022 Sep 29;17(9):e0273147. doi: 10.1371/journal.pone.0273147. eCollection 2022.

ABSTRACT

BACKGROUND: Ethiopia has low malaria prevalence compared to most other malaria-endemic countries in Africa. However, malaria is still a major public health problem in the country. The binary logistic regression model has been widely used to analyse malaria indicator survey (MIS) data. However, most MIS have a hierarchical structure which may result in dependent data. Since this model assumes that conditional on the covariates the malaria statuses of individuals are independent, it ignores potential intra-cluster correlation among observations within a cluster and may generate biased analysis results and conclusions. Therefore, the aim of this study was to quantify the variation in the prevalence of malaria between sample enumeration areas (SEAs) or clusters, the effects of cluster characteristics on the prevalence of malaria using the intra-class correlation coefficient as well as to identify significant factors that affect the prevalence of malaria using the multilevel logistic regression modelling in three major regions of Ethiopia, namely Amhara, Oromia and Southern Nations, Nationalities and Peoples’ (SNNP).

METHODS: Dataset for three regional states extracted from the 2011 Ethiopian National Malaria Indicator Surveys (EMIS) national representative samples was used in this study. It contains 9272 sample individuals selected from these regions. Various multilevel models with random sample SEA effects were applied taking into account the survey design weights. These weights are scaled to address unequal probabilities of selection within clusters. The spatial clustering of malaria prevalence was assessed applying Getis-Ord statistic to best linear unbiased prediction values of model random effects.

RESULTS: About 53.82 and 28.72 per cents of the sampled households in the study regions had no mosquito net and sprayed at least once within the last 12 months, respectively. The results of this study indicate that age, gender, household had mosquito nets, the dwelling has windows, source of drinking water, the two SEA-level variables, i.e. region and median altitude, were significantly related to the prevalence of malaria. After adjusting for these seven variables, about 45% of the residual variation in the prevalence of malaria in the study regions was due to systematic differences between SEAs, while the remaining 55% was due to unmeasured differences between persons or households. The estimated MOR, i.e. the unexplained SEA heterogeneity, was 4.784. This result suggests that there is high variation between SEAs in the prevalence of malaria. In addition, the 80% interval odds ratios (IORs) related to SEA-level variables contain one suggesting that the SEA variability is large in comparison with the effect of each of the variable.

CONCLUSIONS: The multilevel logistic regression with random effects model used in this paper identified five individual / household and two SEA-level risk factors of malaria infection. Therefore, the public health policy makers should pay attentions to those significant factors, such as improving the availability of pure drinking water. Further, the findings of spatial clustering provide information to health policymakers to plan geographically targeted interventions to control malaria transmission.

PMID:36174003 | DOI:10.1371/journal.pone.0273147

PLoS One. 2022 Sep 29;17(9):e0275472. doi: 10.1371/journal.pone.0275472. eCollection 2022.

ABSTRACT

Identifying differentially expressed genes is difficult because of the small number of available samples compared with the large number of genes. Conventional gene selection methods employing statistical tests have the critical problem of heavy dependence of P-values on sample size. Although the recently proposed principal component analysis (PCA) and tensor decomposition (TD)-based unsupervised feature extraction (FE) has often outperformed these statistical test-based methods, the reason why they worked so well is unclear. In this study, we aim to understand this reason in the context of projection pursuit (PP) that was proposed a long time ago to solve the problem of dimensions; we can relate the space spanned by singular value vectors with that spanned by the optimal cluster centroids obtained from K-means. Thus, the success of PCA- and TD-based unsupervised FE can be understood by this equivalence. In addition to this, empirical threshold adjusted P-values of 0.01 assuming the null hypothesis that singular value vectors attributed to genes obey the Gaussian distribution empirically corresponds to threshold-adjusted P-values of 0.1 when the null distribution is generated by gene order shuffling. For this purpose, we newly applied PP to the three data sets to which PCA and TD based unsupervised FE were previously applied; these data sets treated two topics, biomarker identification for kidney cancers (the first two) and the drug discovery for COVID-19 (the thrid one). Then we found the coincidence between PP and PCA or TD based unsupervised FE is pretty well. Shuffling procedures described above are also successfully applied to these three data sets. These findings thus rationalize the success of PCA- and TD-based unsupervised FE for the first time.

PMID:36173994 | DOI:10.1371/journal.pone.0275472

PLoS One. 2022 Sep 29;17(9):e0268150. doi: 10.1371/journal.pone.0268150. eCollection 2022.

ABSTRACT

INTRODUCTION: Hypertension is one global public health emergency disease, and is one of the most critical factors for chronic diseases such as cardiovascular disease, stroke, arrhythmias, heart failure, and renal diseases. Hypertension affects quality of life of patients, however there is limited evidence on the factors that affect health related quality of life among hypertensive patients. As a result, the purpose of this study is to look into factors that affect the health-related quality of life of adult hypertensive patients.

METHODS: An institutional based cross-sectional study was conducted in Dessie City public health facilities from March to April 2021 with the total samples size of 376 hypertensive patients. Simple random sampling technique was employed to select study participants. World health organization health related quality of life 26 items were used to measure outcome variable. Simple linear regression analysis was done and forwarded to multivariable linear regression analysis at p-value<0.2. In multivariable linear regression analysis variables whose p-value less than 0.05 at 95% confidence interval with unstandardized β-coefficient were declared as statistically significant.

RESULTS: A total of 360 hypertensive patients were included in the study. The mean scores of physical, psychological, social and environmental domains were 42.93, SD (18.86), 51.78, SD (20.40), 57.31, SD (20.20) and 48.15, SD (16.26), respectively. Age, duration of antihypertensive treatment, low social support, physical inactivity, co-morbidity, being widow, khat chewing, and being single had a significant association with lower health related quality of life.

CONCLUSION AND RECOMMENDATIONS: The health-related quality of life of hypertensive patients were found low in all domains. The findings indicate the necessity for health professionals, government, non-governmental organizations and community to pay more attention to patients’ quality of life, seeking changes in the therapeutic approach in general.

PMID:36173961 | DOI:10.1371/journal.pone.0268150

J Food Prot. 2022 Sep 29. doi: 10.4315/JFP-22-111. Online ahead of print.

ABSTRACT

Microbial challenge studies using nonpathogenic surrogates provide a practical means for validating thermally based pathogen controls for low-moisture foods (LMFs). Because the relative thermal resistance, or kill ratio, of Enterococcus faecium NRRL B-2354 (a nonpathogenic surrogate) to Salmonella is greatly influenced by food composition, this study assessed relative thermal resistance of a five-strain Salmonella cocktail and E. faecium in skim milk powder (SMP), lactose-free skim milk powder (LSMP), 90% milk protein isolate (MPI), and lactose powder (LP). The impact of sugar composition (lactose vs. glucose-galactose) on resuscitation of bacterial survivors, using SMP and LSMP, was also determined. Dairy powders were inoculated with agar-grown cultures, mixed, pre-equilibrated at 0.25 water activity (aw), ground to achieve homogeneity, re-equilibrated, and subjected to isothermal treatment. After enumeration on nonselective differential media, log-linear and Bigelow models were fit to the survivor data via one-step global regression. Water activity (aw) changes and glass transition temperature (Tog) were assessed at elevated temperatures using uninoculated, equilibrated powder samples. Estimated D90°C values were ~2× higher for E. faecium (P < 0.05) than Salmonella in SMP, LP, and MPI, but statistically similar (P > 0.05) in LSMP. Addition of sugars to recovery media did not influence survivor resuscitation from heat-treated SMP and LSMP, confirming that microbial inactivation was impacted primarily by the thermal treatment, not the recovery step. Thermally induced changes in aw were seen only for LP and MPI, with the glass transition temperature observed only for SMP and MPI. In conclusion, rather than always requiring greater lethality of E. faecium than Salmonella, these findings suggest that sufficient pathogen controls for low-moisture foods can also be validated by thoroughly documenting the appropriate kill ratios of E. faecium to Salmonella.

PMID:36173901 | DOI:10.4315/JFP-22-111

JMIR Res Protoc. 2022 Sep 29;11(9):e38190. doi: 10.2196/38190.

ABSTRACT

BACKGROUND: A subarachnoid hemorrhage is a hemorrhage in the subarachnoid space that is often caused by the rupture of an aneurysm. Patients who survive a subarachnoid hemorrhage have a high risk of complications and a negative long-term outcome.

OBJECTIVE: The aim of the Imaging, Cognition and Outcome of Neuropsychological functioning after Subarachnoid hemorrhage (ICONS) study is to investigate whether and to what extent deficits exist in multiple domains after subarachnoid hemorrhage, including cognition, emotion and behavior, and to investigate whether brain damage can be detected in patients with subarachnoid hemorrhage. We aim to determine which early measures of cognition, emotion and behavior, and brain damage in the subacute stage play a role in long-term recovery after subarachnoid hemorrhage. Recovery is defined as functioning at a societal participation level, with a focus on resuming and maintaining work, leisure activities, and social relationships over the long term.

METHODS: The ICONS study is an observational, prospective, single-center cohort study. The study includes patients with subarachnoid hemorrhage admitted to the Neurosurgery Unit of the University Medical Centre Groningen in the Netherlands. The inclusion criteria include diagnosis of an aneurysmal subarachnoid hemorrhage or an angiographically negative subarachnoid hemorrhage, sufficient ability in the Dutch language, and age older than 18 years. Patients will undergo neuropsychological assessment and magnetic resonance imaging 6 months after the subarachnoid hemorrhage. Furthermore, patients will be asked to fill in questionnaires on multiple psychosocial measures and undergo a structured interview at 6 months, 1 year, and 2 years after the subarachnoid hemorrhage. The primary outcome measure of the ICONS study is societal participation 1 year after the subarachnoid hemorrhage, measured with the Dutch version of the Impact on Participation and Autonomy questionnaire.

RESULTS: The study was launched in December 2019 and recruitment is expected to continue until June 2023. At the time of the acceptance of this paper, 76 patients and 69 healthy controls have been included. The first results are expected in early 2023.

CONCLUSIONS: The ICONS study is the first to collect and combine data after subarachnoid hemorrhage in a variety of domains, including cognition, emotion and behavior, and brain damage. The results will contribute to a more comprehensive understanding of the consequences of both aneurysmal subarachnoid hemorrhage and angiographically negative subarachnoid hemorrhage, which may ultimately optimize timely treatment for this patient group by setting realistic and attainable goals to improve daily functioning.

TRIAL REGISTRATION: Netherlands Trial Register NL7803; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7803.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38190.

PMID:36173673 | DOI:10.2196/38190

JAMA Otolaryngol Head Neck Surg. 2022 Sep 29. doi: 10.1001/jamaoto.2022.2561. Online ahead of print.

ABSTRACT

IMPORTANCE: In clinical practice, assessment schedules are often arbitrarily determined after definitive treatment of head and neck cancer (HNC), producing heterogeneous and inconsistent surveillance plans.

OBJECTIVE: To establish an optimal assessment schedule for patients with definitively treated locally advanced HNC, stratified by the primary subsite and HPV status, using a parametric model of standardized event-free survival curves.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study including 2 tertiary referral hospitals and a total of 673 patients with definitive locoregional treatment of locally advanced HNC (227 patients with nasopharyngeal cancer [NPC]; 237 patients with human papillomavirus-positive oropharyngeal cancer [HPV+ OPC]; 47 patients with HPV-negative [HPV-] OPC; 65 patients with hypopharyngeal cancer [HPC]; and 97 patients with laryngeal cancer [LC]). Patients had received primary treatment in 2008 through 2019. The median (range) follow-up duration was 57.8 (6.4-158.1) months. Data analyses were performed from April to October 2021.

MAIN OUTCOMES AND MEASURES: Tumor recurrence and secondary malignant neoplasms. Event-free survival was defined as the period from the end of treatment to occurrence of any event. Event-free survival curves were estimated using a piecewise exponential model and divided into 3 phases of regular follow-up. A 5% event rate criterion determined optimal follow-up time point and interval.

RESULTS: The median (range) age of the 673 patients at HNC diagnosis was 58 (15-83) years; 555 (82.5%) were men; race and ethnicity were not considered. The event rates of NPC, HPV+ OPC, HPV- OPC, HPC, and LC were 18.9% (43 of 227), 14.8% (35 of 237), 36.2% (17 of 47), 44.6% (29 of 65), and 30.9% (30 of 97), respectively. Parametric modeling demonstrated optimal follow-up intervals for HPC, LC, and NPC, respectively, every 2.1, 3.2, and 6.1 months; 3.7, 5.6, and 10.8 months; and 9.1, 13.8, and 26.5 months until 16.5, 16.5 to 25.0, and 25.0 to 99.0 months posttreatment (open follow-up thereafter). For HPV- OPC, assessment was recommended every 2.7, 4.8, and 11.8 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. In contrast, HPV+ OPC optimal intervals were every 7.7, 13.7, and 33.7 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. Five, 4, 12, 15, and 10 follow-up visits were recommended for NPC, HPV+ OPC, HPV- OPC, HPC, and LC, respectively.

CONCLUSIONS AND RELEVANCE: This retrospective cohort study using parametric modeling suggests that the HNC assessment schedules should be patient tailored and evidence based to consider primary subsites and HPV status. Given limited health care resources and rising detection rates and costs of HNC, the guidelines offered by these findings could benefit patients and health systems and aid in developing future consensus guidelines.

PMID:36173618 | DOI:10.1001/jamaoto.2022.2561

Syst Biol. 2022 Sep 29:syac066. doi: 10.1093/sysbio/syac066. Online ahead of print.

ABSTRACT

The correlation between two characters is often interpreted as evidence that there exists a significant and biologically important relationship between them. However, Maddison and FitzJohn (2015) recently pointed out that evidence of correlated evolution between two categorical characters is often spurious, particularly, when the dependent relationship stems from a single replicate deep in time. Here we will show that there may, in fact, be a statistical solution to the problem posed by Maddison and FitzJohn (2015) naturally embedded within the expanded model space afforded by the hidden Markov model (HMM) framework. We demonstrate that the problem of single unreplicated evolutionary events manifests itself as rate heterogeneity within our models and that this is the source of the false correlation. Therefore, we argue that this problem is better understood as model misspecification rather than a failure of comparative methods to account for phylogenetic pseudoreplication. We utilize HMMs to develop a multi-rate independent model which, when implemented, drastically reduces support for correlation. The problem itself extends beyond categorical character evolution, but we believe that the practical solution presented here may lend itself to future extensions in other areas of comparative biology.

PMID:36173613 | DOI:10.1093/sysbio/syac066

Clin Drug Investig. 2022 Sep 29. doi: 10.1007/s40261-022-01201-2. Online ahead of print.

ABSTRACT

BACKGROUND: Unprotected and fragile elderly people in nursing homes experienced the highest mortality rates during the initial coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: Our aim was to study the role of two oral anti-inflammatory drugs, colchicine and prednisone, in elderly patients with COVID-19 in geriatric centers.

METHODS: A phase II/III, randomized, controlled, multicenter clinical trial was performed in a geriatric population comparing the efficacy and safety of an oral combination of prednisone (60 mg/day for 3 days) and colchicine (at loading doses of 1-1.5 mg/day for 3 days, followed by 0.5 mg/day for 11 days) with the standard treatment, based on intravenous dexamethasone. Primary endpoints assessed the efficacy in reducing death or the modified endpoint death/therapeutic failure to the study drugs over a 28-day period, while secondary endpoints included safety, laboratory changes, and additional therapies used.

RESULTS: Fifty-four patients (35 female/19 male) were enrolled, 25 (46.3%) of whom were allocated to the experimental arm and 29 (53.7%) to the control arm. At day 28, no differences in deaths were observed. The combination of mortality or therapeutic failure occurred in 12 (45.13%) patients receiving dexamethasone and 6 (28.13%) patients receiving colchicine/prednisone, resulting in a reduction of risk difference (RD) of – 17% (p = 0.17), with an average reduction of 39% (risk ratio [RR] 0.61) in patients receiving colchicine/prednisone (p = 0.25). Control patients received higher amounts of additional glucocorticoids (p = 0.0095) over a longer time frame (p = 0.0003). Colchicine/prednisone significantly reduced ferritin levels at day 14, as well as D-dimer and lactate dehydrogenase (LDH) levels at day 28. Adverse events were similar in both groups.

CONCLUSIONS: The combination colchicine/prednisone compared with intravenous dexamethasone has shown a remarkable trend to increase disease survival over a 28-day period in elderly patients requiring oxygen therapy in geriatric centers, without safety issues.

CLINICAL TRIAL REGISTRY: Clinical Trials Registration Number: NCT04492358.

PMID:36173596 | DOI:10.1007/s40261-022-01201-2

Dermatol Ther (Heidelb). 2022 Sep 29. doi: 10.1007/s13555-022-00815-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The shortcomings of standardized sunscreen testing have been discussed in recent years, noting differences between how sunscreens perform in indoor clinical (in vivo) laboratory testing compared with real-life conditions. We previously developed an outdoor clinical method for ranking sunscreens by performance level. We used this method to test the performance of a new broad-spectrum sunscreen against International Organization for Standardization (ISO) reference products P3, P5 and P8.

METHODS: Sixty-five healthy volunteers with individual typology angle (ITA) ≥ 28° (light to intermediate skin colour) participated in an outdoor study in Mauritius. Test areas were marked on their backs, which were treated with the different products: one commercially available broad-spectrum sun protection factor (SPF) 50 sunscreen [investigational product (IP)] and the three reference products P3 (SPF 15), P5 (SPF 30) and P8 (SPF 50+) from ISO norm 24444:2019 for SPF testing. The test areas were exposed for 2-3 h, depending on the baseline skin colour. They were also compared with an unprotected positive control area and a non-exposed negative control area. Clinical and colorimetry assessment of erythema and pigmentation were performed at 24 h and 8 days, respectively.

RESULTS: Overall, according to this outdoor clinical testing method, the sunscreens’ efficacy was ranked in an appropriate order given their established SPF levels, with higher SPFs giving greater protection against erythema and pigmentation. Between the different levels of SPF, the differences were statistically significant, for both clinical and colorimetry assessments. The new broad-spectrum SPF 50 IP performed similarly to the SPF 50+ (P8) reference product. Even the highest SPF products, SPF 50 and SPF 50+, had some instances of photoprotection failure.

CONCLUSION: These findings confirm the feasibility of this outdoor clinical testing method in ranking sunscreens and provide further evidence, in addition to standardized SPF and UVA protection factor (UVAPF) testing, on how this new broad-spectrum SPF 50 sunscreen performs in extreme outdoor solar exposure: in line with reference product P8 (SPF 50+).

TRIAL REGISTRATION NO: ISRCTN95394014.

PMID:36173595 | DOI:10.1007/s13555-022-00815-w

Fish Physiol Biochem. 2022 Sep 29. doi: 10.1007/s10695-022-01126-9. Online ahead of print.

ABSTRACT

An 8-week growth experiment was conducted to investigate the effects of dietary leucine on growth performance, body composition, and gene expression of hepatic nutrient metabolism in the largemouth bass (Micropterus salmoides). Six isonitrogenous (49.87%) diets with graded leucine levels (2.62, 3.07, 3.60, 3.87, 4.20, 4.71% of dry diet) were fed to triplicate groups with 20 juvenile fish (20.00 ± 0.13 g). The results revealed that the specific growth rate (SGR) and weight gain (WG) increased significantly with increasing dietary leucine levels, reached their maximal value in the Leu-4.20% groups, and then decreased slightly. Although the feed conversion ratio (FCR) showed decreasing trends, no significant difference was detected. Leucine supplementation significantly improved the content of body protein and total plasma protein (TP). Additionally, a higher expression level of target of rapamycin (TOR) and ribosomal protein S6 (S6) mRNA was observed in the Leu-3.87% and Leu-4.20% diets, whereas the GCN2 (general control nonderepressible2 kinase) and AFT4 (activating transcription factor 4) mRNA expression levels were suppressed. The lipid content of the body was not influenced by leucine levels, whereas the content of total triglyceride (TG) first decreased significantly with increasing dietary leucine levels from 2.62 to 3.87% and then increased with increasing leucine levels (4.20% to 4.71%). The total cholesterol (TC) and low-density lipoproteins (LDL) trended in a similar direction but did not achieve statistical significance (P > 0.05). The expression of insulin receptor substrate 1 (IRS-1) was significantly elevated by dietary leucine levels, while protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) expression was inconsistently upregulated. Furthermore, leucine supplementation decreased plasma glucose and hepatic glycogen contents, and the expression levels of glucokinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6pase) were significantly inhibited at 4.20% and 4.71% leucine diets. Analyses of the change in SGR and FCR using the quadratic regression model estimated that the optimum dietary leucine requirement of juvenile largemouth bass was 4.42% and 4.63% of the dry diet (8.86% and 9.28% of dietary protein), respectively.

PMID:36173585 | DOI:10.1007/s10695-022-01126-9