Category: Nevin Manimala

J Gen Intern Med. 2021 May 26. doi: 10.1007/s11606-021-06915-1. Online ahead of print.

ABSTRACT

BACKGROUND: Few studies have investigated the relationship between industry funding/conflicts of interest and authors’ positions in opinion pieces on drug safety. Harmful effects of varenicline, a treatment for smoking cessation, have been highly contested.

OBJECTIVE: To examine the association between pharmaceutical industry funding/authors’ financial conflicts of interest and position on varenicline in opinion articles, especially in relation to the minimization of harms; to assess whether opinion pieces on drug safety issues written by authors with conflicts of interest are more frequently cited in the news or social media.

DESIGN: Cross-sectional analysis.

PARTICIPANTS: English language opinion pieces and narrative reviews about varenicline published between May 2006 and February 2019.

MAIN MEASURES: Odds ratios and 95% confidence intervals; the Mann-Whitney two-sample statistic was used to test for differences in Altmetric scores, a measure of media attention.

KEY RESULTS: Of the 221 included articles, 30.3% (67) disclosed the funding source and 62.9% (139) disclosed authors’ conflicts of interest. Authors of opinion pieces on varenicline who reported financial ties to the pharmaceutical industry (as a conflict of interest or funding source) were more likely to minimise the cardiovascular and psychiatric risk of varenicline compared to those without conflicts of interest or industry funding (OR: 4.00; 95% CI: 1.32 to 12.16 for cardiovascular risk; OR: 8.51; 95% CI: 3.79 to 19.11 for psychiatric risk). These associations persisted in sensitivity analyses. No statistically significant difference in Altmetric score was found between articles with (mean 15.83, median 3) and without (mean 11.90, median 1) conflicts of interest, indicating similar media attention (p-value=0.11).

CONCLUSIONS: We found that authors with financial ties to drug companies were more likely to publish opinion pieces that minimised harms of varenicline. These results raise questions about journals’ editorial policies to accept reviews of treatments from authors with financial relationships with manufacturers.

PMID:34037923 | DOI:10.1007/s11606-021-06915-1

Can J Public Health. 2021 May 26. doi: 10.17269/s41997-021-00527-2. Online ahead of print.

ABSTRACT

OBJECTIVES: Poor housing conditions and household crowding have been identified as important health concerns for Indigenous populations in many countries but have not been explored in relation to adverse birth outcomes in these populations. We investigated housing conditions and adverse birth outcomes in a nationally representative sample of Indigenous people in Canada.

METHODS: Data were from a cohort of births between May 2004 and May 2006 created by linking birth and infant death registration data with the 2006 Canadian census. Log-binomial regression was used to examine associations between housing variables (persons per room and needed household repairs) and three adverse birth outcomes: preterm birth (PTB), small-for-gestational-age (SGA) birth, and infant mortality. Separate regression models were run for First Nations, Métis and Inuit mothers, with adjustment for parity and parental socio-economic variables.

RESULTS: Need for major household repairs was associated with a slightly increased risk of PTB among First Nations and Métis mothers (adjusted RRs 1.12 and 1.13, respectively; 95% CI 0.94-1.34 and 0.89-1.44, respectively) and a moderately increased risk of infant death in all three groups (aRR = 1.69, 95% CI 1.00-2.85). Household crowding was also associated with a slightly elevated risk of PTB in all three groups (aRR = 1.10, 95% CI 0.95-1.29) and with an increased risk of infant mortality among First Nations (aRR = 1.57, 95% CI 0.97-2.53).

CONCLUSION: This study highlights the need to improve understanding of links between housing conditions and perinatal health outcomes in Indigenous populations, including examining cause-specific infant mortality in relation to housing characteristics.

PMID:34037966 | DOI:10.17269/s41997-021-00527-2

Bull Math Biol. 2021 May 26;83(7):80. doi: 10.1007/s11538-021-00912-5.

ABSTRACT

Mechanical and mechanochemical models of pattern formation in biological tissues have been used to study a variety of biomedical systems, particularly in developmental biology, and describe the physical interactions between cells and their local surroundings. These models in their original form consist of a balance equation for the cell density, a balance equation for the density of the extracellular matrix (ECM), and a force-balance equation describing the mechanical equilibrium of the cell-ECM system. Under the assumption that the cell-ECM system can be regarded as an isotropic linear viscoelastic material, the force-balance equation is often defined using the Kelvin-Voigt model of linear viscoelasticity to represent the stress-strain relation of the ECM. However, due to the multifaceted bio-physical nature of the ECM constituents, there are rheological aspects that cannot be effectively captured by this model and, therefore, depending on the pattern formation process and the type of biological tissue considered, other constitutive models of linear viscoelasticity may be better suited. In this paper, we systematically assess the pattern formation potential of different stress-strain constitutive equations for the ECM within a mechanical model of pattern formation in biological tissues. The results obtained through linear stability analysis and the dispersion relations derived therefrom support the idea that fluid-like constitutive models, such as the Maxwell model and the Jeffrey model, have a pattern formation potential much higher than solid-like models, such as the Kelvin-Voigt model and the standard linear solid model. This is confirmed by the results of numerical simulations, which demonstrate that, all else being equal, spatial patterns emerge in the case where the Maxwell model is used to represent the stress-strain relation of the ECM, while no patterns are observed when the Kelvin-Voigt model is employed. Our findings suggest that further empirical work is required to acquire detailed quantitative information on the mechanical properties of components of the ECM in different biological tissues in order to furnish mechanical and mechanochemical models of pattern formation with stress-strain constitutive equations for the ECM that provide a more faithful representation of the underlying tissue rheology.

PMID:34037880 | DOI:10.1007/s11538-021-00912-5

Int J Clin Oncol. 2021 May 26. doi: 10.1007/s10147-021-01935-7. Online ahead of print.

ABSTRACT

BACKGROUND: Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols.

METHODS: Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate.

RESULTS: Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1-6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively.

CONCLUSION: This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.

PMID:34037884 | DOI:10.1007/s10147-021-01935-7

Int J Cardiovasc Imaging. 2021 May 26. doi: 10.1007/s10554-021-02289-x. Online ahead of print.

ABSTRACT

External Counterpulsation (ECP) is one of the therapeutic options in patients with refractory angina inadequately controlled by medical, interventional, or surgical therapy. The 2D Speckle Tracking Echocardiography (2D-STE) method is considered superior in assessing clinical improvement. We would like to evaluate any improvement of myocardial intrinsic function using 2D-STE in patients underwent standard ECP protocol (35 sessions). We conducted a double-blind randomized controlled trial. Patients with refractory angina who could not be revascularized conventionally were randomized into two groups: (1) the ECP group (300 mmHg) and (2) the Sham/control group (75 mmHg). ECP standard therapy was given for 35 sessions (1 h/day/session). The 2D-STE data, including longitudinal strain and post systolic index (PSI) were obtained before and after therapy. 43 subjects were analyzed, with 22 subjects in ECP group and 21 control subjects (Sham group). A homogenous baseline strain was found either globally (12.42 ± 4.55 vs 12.00 ± 4.92 [- %]; P = 0.774) or segmentally/regionally (12.63 (0.01-25.16) vs 12.43 (0.01-27.20) [- %]; P = 0.570). There was no statistically significant improvement between groups in the left ventricle longitudinal strain globally (P = 0.535) and segmentally/regionally (P = 0.434). PSI parameters showed improvement in the ECP group (P = 0.049), and segments with PSI ≥ 20% seemed to improve longitudinal strains in the ECP group after therapy (P = 0.042). In conclusion, 35 ECP therapy sessions did not improve either global or segmental/regional left ventricular mechanical function in patients with refractory angina. However, the mechanical function of myocardial segments with PSS tends to improve after ECP therapy.

PMID:34037889 | DOI:10.1007/s10554-021-02289-x

J Math Biol. 2021 May 26;82(7):64. doi: 10.1007/s00285-021-01613-2.

ABSTRACT

We analyze ecological systems that are influenced by random environmental fluctuations. We first provide general conditions which ensure that the species coexist and the system converges to a unique invariant probability measure (stationary distribution). Since it is usually impossible to characterize this invariant probability measure analytically, we develop a powerful method for numerically approximating invariant probability measures. This allows us to shed light upon how the various parameters of the ecosystem impact the stationary distribution. We analyze different types of environmental fluctuations. At first we study ecosystems modeled by stochastic differential equations. In the second setting we look at piecewise deterministic Markov processes. These are processes where one follows a system of differential equations for a random time, after which the environmental state changes, and one follows a different set of differential equations-this procedure then gets repeated indefinitely. Finally, we look at stochastic differential equations with switching, which take into account both the white noise fluctuations and the random environmental switches. As applications of our theoretical and numerical analysis, we look at competitive Lotka-Volterra, Beddington-DeAngelis predator-prey, and rock-paper-scissors dynamics. We highlight new biological insights by analyzing the stationary distributions of the ecosystems and by seeing how various types of environmental fluctuations influence the long term fate of populations.

PMID:34037835 | DOI:10.1007/s00285-021-01613-2

Eur J Orthop Surg Traumatol. 2021 May 26. doi: 10.1007/s00590-021-03010-3. Online ahead of print.

ABSTRACT

PURPOSE: Back pain may both decrease patient satisfaction after TKA and confound outcome assessment in satisfied patients. Our primary objective was to determine whether preoperative back pain is associated with differences in postoperative patient-reported outcome measures (PROMs).

METHODS: We retrospectively reviewed 234 primary TKA patients who completed PROMs preoperatively and 12 weeks postoperatively, which included a back pain questionnaire, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and the Forgotten Joint Score-12 (FJS-12). Cohorts were defined based on the severity of preoperative back pain (none, mild, moderate and severe) and compared. Demographics were compared using ANOVA and Chi-square analysis. Univariate ANCOVA analysis was utilized to compare PROMs while accounting for significant demographic differences.

RESULTS: Both preoperative KOOS JR scores (none: 47.90, mild: 47.61, moderate: 44.61 and severe: 38.70; p = 0.013) and 12-week postoperative KOOS JR scores (none: 61.24, mild: 64.94, moderate: 57.48 and severe: 57.01; p = 0.012) had a statistically significant inverse relationship with regard to the intensity of preoperative back pain. Although FJS-12 scores at the 12-week postoperative period trended lower with increasing levels of preoperative back pain (p = 0.362), it did not reach statistical significance. Patients who reported severe back pain preoperatively achieved the largest delta improvement from baseline compared to those with lesser pain intensity (p = 0.003). Patients who had a 2-grade improvement in their back pain achieved significantly higher KOOS JR scores 12 weeks postoperatively compared to patients with either 1-grade or no improvement (63.53 vs. 55.98; p = 0.042). Both preoperative (47.99 vs. 41.11; p = 0.003) and 12-week postoperative (64.06 vs. 55.73; p < 0.001) KOOS JR scores were statistically higher for those who reported mild or no back pain pre-and postoperatively than those who reported moderate or severe back pain pre-and postoperatively.

CONCLUSION: Knee pain and back pain both exert negative effects on outcome instruments designed to measure pain and function. Although mean improvement from pre- to postoperative KOOS JR scores for patients with severe pre-existing back pain was higher than their counterparts, this statistical difference is likely not clinically significant. This implies that all patients may experience similar benefits from TKA despite the presence or absence of back pain. Attempts to measure TKA outcomes using PROMs should seek to control for lumbago and other sources of body pain. Level of Evidence IIIRetrospective Cohort Study.

PMID:34037858 | DOI:10.1007/s00590-021-03010-3

Eur Radiol. 2021 May 26. doi: 10.1007/s00330-021-07948-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the ability of CT radiomic features extracted from peritumoral parenchyma of 2 mm and 5 mm distinguishing invasive adenocarcinoma (IAC) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA).

METHODS: For this retrospective study, 121 lung adenocarcinomas appearing as ground-glass nodules on thin-section CT were evaluated. Quantitative radiomic features were extracted from the peritumoral parenchymal region of 2 mm and 5 mm on CT imaging, and the radiomic models of External2 and External5 were constructed. The ROC curves were used to evaluate the performance of different models. Differences between the AUCs were evaluated using DeLong’s method.

RESULTS: The radiomic scores of IAC were statistically higher than those of MIA/AIS in both the External2 and External5 models. The AUCs of the External2 and External5 models were 0.882, 0.778 in the training cohort and 0.888, 0.804 in the validation cohort, respectively. The AUC of the External2 model was not statistically different from the External5 model both in the training cohort (p = 0.116) and validation cohort (p = 0.423).

CONCLUSIONS: The radiomic features extracted from the peritumoral region of 2 mm and 5 mm at thin-section CT showed good predictive values to differentiate the IAC from AIS/MIA. The radiomic features from the peritumoral region of 5 mm provide no additional benefit in distinguishing IAC from MIA/AIS than that of the 2 mm region.

KEY POINTS: • The radiomic models from various peritumoral lung parenchyma were developed and validated to predict invasiveness of adenocarcinoma. • The peritumoral parenchyma of lung adenocarcinoma may contain useful information. • Radiomics from peritumoral lung parenchyma of 5 mm provides no added efficiency of the prediction for invasiveness of lung adenocarcinoma.

PMID:34037830 | DOI:10.1007/s00330-021-07948-0

Transl Behav Med. 2021 May 26:ibab028. doi: 10.1093/tbm/ibab028. Online ahead of print.

ABSTRACT

Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as ≥ 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.

PMID:34037786 | DOI:10.1093/tbm/ibab028

J Trop Pediatr. 2021 May 17;67(2):fmab044. doi: 10.1093/tropej/fmab044.

ABSTRACT

BACKGROUND: Structural congenital heart defects (CHD) take a huge toll of congenital defects in children in India. Limited information is available regarding modifiable risk factors for its causation. This study was planned with an aim to determine the prevalence of congenital rubella infection in Indian infants with structural CHD’s.

METHODOLOGY: This cross-sectional, observational study was conducted at a tertiary care hospital in Northern India over 1 year period (1 July 2016 to 30 June 2017). Infants <6 months with structural CHD were enrolled after taking informed consent from their mothers. Blood samples were collected from mother-child binomials and tested for rubella IgM and IgG antibodies.

RESULTS: A total of 80 infants (M : F = 56 : 24), having mean age 69.4 (±56.5) days; were enrolled. In these infants, prevalence of congenital rubella infection (either infant’s IgM rubella positive or infant’s IgG rubella titers higher than mother’s) was 8.75% (7/80). A total of 12.5% of studied mothers were seronegative for rubella IgG antibodies. Statistically significant association was found between the occurrence of congenital rubella and cataract (p = 0.0039), splenomegaly (p = 0.007) and microcephaly (p = 0.0084) in infants having structural CHD.

CONCLUSIONS: Congenital rubella syndrome still remains an important modifiable cause for structural CHD in India. Sincere efforts for rubella elimination via further strengthening current vaccination strategy would help in decreasing burden of structural CHD in India.

PMID:34037788 | DOI:10.1093/tropej/fmab044