Category: Nevin Manimala

Am Nat. 2022 Jan;199(1):108-125. doi: 10.1086/717178. Epub 2021 Nov 22.

ABSTRACT

AbstractEfforts to explain animal population cycles often invoke consumer-resource theory, which has shown that consumer-resource interactions alone can drive population cycles. Eco-evo theory instead argues that population cycles are partly driven by fluctuating selection for resistance in the resource, but support for eco-evo theory has come almost entirely from laboratory microcosms. Here we ask, Can eco-evo theory explain population cycles in the field? We compared the ability of eco-evo models and classical “eco-only” models to explain data on cycles in the insect Lymantria dispar, in which outbreaks of the insect are terminated by a fatal baculovirus. We carried out a statistical comparison of the ability of eco-only and eco-evo models to explain combined data from L. dispar outbreak cycles and baculovirus epizootics (epidemics in animals). Both models require high host variation in resistance to explain the epizootic data, but high host variation in the eco-evo model leads to consistently accurate predictions of outbreak cycles, whereas in the presence of high host variation the eco-only model can explain outbreak cycles only by invoking high levels of stochasticity, which leads to highly variable and often inaccurate predictions of outbreak cycles. Our work provides statistically robust evidence that eco-evo models can explain population cycles in the field.

PMID:34978965 | DOI:10.1086/717178

Dent Med Probl. 2021 Dec 31. doi: 10.17219/dmp/135652. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the SBS of pre-sintered and sintered zirconia to a selfadhesive resin cement after various treatment (air abrasion and the Nd:YAG laser irradiation at varying power levels -1 W, 2 W and 3 W).

MATERIAL AND METHODS: Ninety-nine zirconia specimens were prepared and divided into 3 groups: control (with no surface treatment); and pre-sintered and sintered groups with surface treatment. Surface treatment was applied before sintering in the pre-sintered group and after sintering in the sintered group. After following all protocols, a resin cement was layered on the zirconia surface. Shear bond strength was measured using a universal testing machine. The results were subjected to the statistical analysis. The surface topography and phase transformation of zirconia were evaluated using the atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses after surface treatment.

RESULTS: The laser irradiation (3 W, 1 W and 2 W) of the pre-sintered zirconia surface resulted in the highest SBS values (p < 0.001), while the lowest SBS values were obtained with airborne particle abrasion of the pre-sintered and sintered zirconia surfaces.

CONCLUSIONS: Laser irradiation increased the SBS of pre-sintered zirconia to a resin cement. Surface treatment with air abrasion had a lesser effect on the SBS values.

PMID:34978766 | DOI:10.17219/dmp/135652

Antimicrob Agents Chemother. 2022 Jan 3:AAC0182121. doi: 10.1128/AAC.01821-21. Online ahead of print.

ABSTRACT

The active metabolites of primaquine, in particular 5-hydroxyprimaquine, likely responsible for clearance of dormant hypnozoites, are produced through the hepatic CYP450 2D6 (CYP2D6) enzymatic pathway. With the inherent instability of 5-hydroxyprimaquine, a stable surrogate, 5,6 orthoquinone, can now be detected and measured in the urine as part of primaquine pharmacokinetic studies. This study performed CYP450 2D6 genotyping and primaquine pharmacokinetic testing, to include urine 5,6 orthoquinone, in 27 healthy adult Cambodians, as a preliminary step to prepare for future clinical studies assessing primaquine efficacy for Plasmodium vivax infections. The CYP2D6 *10 reduced activity allele was found in 57% of volunteers, and the CYP2D6 genotypes were dominated by *1/*10 (33%) and *10/*10 (30%). Predicted phenotypes were evenly split between Normal Metabolizer (NM) and Intermediate Metabolizer (IM) except one volunteer with a gene duplication and unclear phenotype, classifying as either IM or NM. Median plasma PQ area under the curve (AUC) was lower in the NM group (460 hr*ng/mL) compared to the IM group (561 hr*ng/mL), although not statistically significant. Similar to what has been found in the US study, no 5,6 orthoquinone was detected in the plasma. The urine creatinine-corrected 5,6 orthoquinone AUC in the NM group was almost three times higher than in the IM group, with peak measurements (T_max) at 4 hours. Although there is variation among individuals, future studies examining the relationship between the levels of urine 5,6 orthoquinone and primaquine radical cure efficacy could result in a metabolism biomarker predictive of radical cure.

PMID:34978892 | DOI:10.1128/AAC.01821-21

Trop Med Int Health. 2022 Jan 3. doi: 10.1111/tmi.13716. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the effect of adaptations to a person-centred care with short oral regimens on retention in care for rifampicin-resistant TB (RR-TB) in Kandahar province, Afghanistan.

METHODS: The study included people with RR-TB registered in the programme between 01 October 2016 and 18 April 2021. From 19 November 2019 the programme implemented a trial investigating the safety and effectiveness of short oral RR-TB regimens. During the trial, person-centred care was adapted. We included data from people living with RR-TB treated in the period before and after the care model was adapted and applied Kaplan-Meier statistics to compare rates of retention in care.

RESULTS: Of 236 patients registered in the RR-TB programme, 146 (61.9%) were registered before and 90 (38.1%) after the model of care was adapted. Before adaptations enhancing person-centred care, pre-treatment attrition was 23.3% (n=34/146), while under the adapted care model it was 5.6% (n=5/90). Attrition on treatment was 22.3% (n=25/112) before adaptations, while during the study period none of the participants were lost to follow-up on treatment and 3.3% died (n=3/90).

CONCLUSIONS: As person-centred care delivery and treatment regimens were adapted to better fit specific contextual challenges and the needs of the target population, retention in care improved among people with RR-TB in Kandahar, Afghanistan.

PMID:34978748 | DOI:10.1111/tmi.13716

Neth Heart J. 2022 Jan 3. doi: 10.1007/s12471-021-01650-y. Online ahead of print.

ABSTRACT

In the Netherlands, the coronavirus disease 2019 (COVID‑19) pandemic has resulted in excess mortality nationwide. Chronic heart disease patients are at risk for a complicated COVID‑19 course. The current study investigates all-cause mortality among cardiac implantable electronic device (CIED) patients during the first peak of the pandemic and compares the data to the statistics for the corresponding period in the two previous years. Data of adult CIED patients undergoing follow-up at the Leiden University Medical Centre were analysed. All-cause mortality between 1 March and 31 May 2020 was evaluated and compared to the data for the same period in 2019 and 2018. At the beginning of the first peak of the pandemic, 3,171 CIED patients (median age 70 years; 68% male; 41% ischaemic aetiology) were alive. Baseline characteristics of the 2019 (n = 3,216) and 2018 (n = 3,169) cohorts were comparable. All-cause mortality during the peak of the pandemic was 1.4% compared to 1.6% and 1.4% in the same period in 2019 and 2018, respectively (p = 0.84). During the first peak of the COVID‑19 pandemic, there was no substantial excess mortality among CIED patients in the Leiden area, despite the fact that this is group at high risk for a complicated course of a COVID‑19 infection. Strict adherence to the preventive measures may have prevented substantial excess mortality in these vulnerable patients.

PMID:34978678 | DOI:10.1007/s12471-021-01650-y

Artif Organs. 2022 Jan 3. doi: 10.1111/aor.14165. Online ahead of print.

ABSTRACT

BACKGROUND: A relation between left ventricular assist device inflow cannula malposition and pump thrombus has been reported. This study aimed to investigate if the pump position, derived from chest X-rays in HeartMate 3 (HM3) patients, correlates with neurological dysfunction (ND), ischemic stroke (IS), hemorrhagic stroke (HS) and survival.

METHODS: This analysis was performed on routinely acquired X-rays of 42 patients implanted with a HM3 between 2014 and 2017. Device position was quantified in patients with and without ND from frontal and lateral X-rays characterizing the inflow cannula (IC) and pump in relation to spine, diaphragm or horizontal line. The primary end-point was freedom from stroke and survival one-year after HM3 implantation stratified by pump position.

RESULTS: The analysis of X-rays, 33.5 (41.0) days postoperative, revealed a significant smaller IC angle of HM3 patients with ND vs. no ND (0.1±14.0° vs. 12.9±10.1°, p=0.005). Additionally, the IC angle in the frontal view, IS: 4.1 (20.9)° vs. no IS: 13.8 (7.5)°, p=0.004 was significantly smaller for HM3 patients with IS. Using ROC derived cut-off, IC angle <10° provided 75% sensitivity and 100% specificity (C-statistic=0.85) for predicting IS. Stratified by IC angle, freedom from IS at 12 months was 100% (>10°) and 60% (<10°) respectively (p=0.002). No significant differences were found in any end-point between patients with and without HS. One-year survival was significantly higher in patients with IC angle >10° vs. <10° (100% vs. 71.8%, p=0.012).

CONCLUSIONS: Inflow cannula malposition derived from standard chest X-rays serves as a risk factor for neurological dysfunction, ischemic stroke and worse survival in HM3 patients.

PMID:34978722 | DOI:10.1111/aor.14165

Int J Cardiovasc Imaging. 2022 Jan 3. doi: 10.1007/s10554-021-02518-3. Online ahead of print.

ABSTRACT

Percutaneous Transvenous Mitral Commissurotomy (PTMC) is the first line treatment for rheumatic mitral stenosis (MS). We sought to evaluate (1) changes in 2-dimensional (2D) echocardiographic and strain values and (2) differences in these values for patients in atrial fibrillation (AF) and sinus rhythm (SR) pre, immediately and 6 months post PTMC. Retrospective study of 136 patients who underwent PTMC between 2011 and 2021. We analyzed their 2D echocardiogram, Global Longitudinal Strain (GLS), Left Atrial Reservoir Strain (LAr-S) and Right Ventricle Free Wall Strain (RVFW-S) pre, immediately and 6 months post PTMC. At 6 months, mitral valve area increases from 0.94 ± 0.23 cm² to 1.50 ± 0.42 cm². Ejection fraction (EF) did not change post PTMC (pre; 55.56 ± 6.62%, immediate; 56.68 ± 7.83%, 6 months; 56.28 ± 7.00%, p = 0.218). Even though EF is preserved, GLS is lower pre-procedure; – 11.52 ± 3.74% with significant improvement at 6 months; – 15.16 ± 4.28% (p < 0.001). Tricuspid annular plane systolic excursion (TAPSE) improved at 6 months from 1.95 ± 0.43 to 2.11 ± 0.49 (p = 0.004). RVFW-S increases at 6 months from – 17.37 ± 6.03% to – 19.75 ± 7.19% (p = 0.011). LAr-S improved from 11.23 ± 6.83% pre PTMC to 16.80 ± 8.82% at 6 months (p < 0.001) post PTMC. Pre-procedure patients with AF have lower strain values (More LV, RV and LA dysfunction) with statistically significant difference for LAr-S (p < 0.001), GLS (p < 0.001) and RVFW-S (p < 0.001) than patients in SR. Patients with severe rheumatic MS have subclinical left and right ventricle dysfunction despite preserved EF and relatively normal TAPSE with significant improvement seen at 6 months post PTMC. AF patients have lower baseline strain values than SR patients.

PMID:34978670 | DOI:10.1007/s10554-021-02518-3

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00833-6. Online ahead of print.

ABSTRACT

BACKGROUND: The poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types.

METHODS: Histopathology data from esophageal biopsies obtained 1979-2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference.

RESULTS: In total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2-0.5 for inflammatory changes, and 0.8-2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7-1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8-1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0-4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6-15.5), 12.0 (10.0-14.2) and 30.2 (20.5-42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated.

CONCLUSIONS: For the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC.

PMID:34978667 | DOI:10.1007/s10654-021-00833-6

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00815-8. Online ahead of print.

ABSTRACT

Lifetime risk measures the cumulative risk for developing a disease over one’s lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.

PMID:34978669 | DOI:10.1007/s10654-021-00815-8

Eur J Epidemiol. 2022 Jan 3. doi: 10.1007/s10654-021-00826-5. Online ahead of print.

ABSTRACT

BACKGROUND: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake.

METHODS: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank.

RESULTS: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = – 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = – 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant.

CONCLUSIONS: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

PMID:34978666 | DOI:10.1007/s10654-021-00826-5