Category: Nevin Manimala

Int J Mycobacteriol. 2021 Jul-Sep;10(3):243-254. doi: 10.4103/ijmy.ijmy_108_21.

ABSTRACT

BACKGROUND: Host genetic background plays an important role in susceptibility to intracellular infectious pathogens like Mycobacterium tuberculosis (Mtb). Cellular immune response activation is vital for protection to these pathogens. Interferon-gamma (IFN-γ) plays a crucial role in this activation and preventing the intracellular growth of Mtb. A mutation in the IFN-γ gene, therefore, may lead to increased susceptibility to tuberculosis (TB) that may vary in different ethnic groups and its consequence also varies in pulmonary and extra-pulmonary TB (EPTB). Several IFN-γ gene polymorphisms are investigated for susceptibility to TB, but their associations are not always consistent as its impact may vary from one ethnicity to the other as well as with the type of TB. Hence, we performed a meta-analysis to overcome this problem. The present study involves comprehensive meta-analysis of + 874T/A polymorphism in the IFN-γ gene based on type of TB within five different ethnic groups to show its association with increased susceptibility to TB.

METHODS: Using PubMed and Google Scholar databases, a total of 50 case-control studies were retrieved having 8152 cases and 9755 controls in this meta-analysis. Thirty-eight studies of + 874T/A polymorphism of IFN-γ gene were correlated for Pooled odds ratios with 95% confidence intervals. The polymorphism was analyzed for six genetic models for five major ethnic groups accounting for heterogeneity among studies. Moreover, the sub-group analysis was based on the type of TB within each ethnic group. Trial sequential analysis was also performed for all the sub-groups to estimate the statistical consistency.

RESULTS: IFN-γ +874 T/A polymorphism analysis clearly confirmed the increased association of + 874AA genotype with increased TB risk. This polymorphism also showed significant association in East Asian, European, American, and African ethnic groups whereas no such association was found in Asians. Patients with pulmonary TB (PTB) confirmed the association in East Asians, Africans, and Americans, whereas patients with EPTB showed association in Asian and East Asian populations only.

CONCLUSIONS: This study reaffirms the association of IFN-γ+874 T/A polymorphism with TB risk. It specifically confirms that IFN-γ+874 T/A polymorphism increases the susceptibility of pulmonary infection in Africans and Americans, while the East Asian population is more susceptible to both, pulmonary and EPTB.

PMID:34494562 | DOI:10.4103/ijmy.ijmy_108_21

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2021 Aug;43(4):579-583. doi: 10.3881/j.issn.1000-503X.13076.

ABSTRACT

Objective To evaluate lateral pterygoid muscle(LPM)contraction in the patients with temporomandibular disorders(TMD)based on 3D-T2 weighted imaging(3D-T2WI).Multiplanar reconstruction(MPR)was employed to measure the length of LPM in the images taken in closed-and open-mouth positions. Methods Seventeen TMD patients [age of(29.82±10.70)years,males/females=8/9] and 13 normal volunteers [control,age of(23.54±3.31)years,males/females=6/7] received 3D-T2WI of the temporomandibular joints in closed-and open-mouth positions from November 2019 to April 2020 in Department of Radiology,Hainan Hospital of Chinese PLA General Hospital.According to the position of the discs,the subjects were classified into the following groups:TMD with disc displacement without reduction(TMD-DDwoR),TMD with disc displacement with reduction(TMD-DDwR),TMD without disc displacement(TMDwoDD),and normal control without disc displacement(NCwoDD).MPR was employed to measure the maximal length of the superior belly of LPM.One-way analysis of variance,receiver operating characteristic curve,and permutation test were employed for the statistical analyses. Results The contraction of LPM was significantly shorter in TMD-DDwoR group [(3.36±1.96)mm] than in TMDwoDD group [(7.90±3.95)mm],NCwoDD group [(8.77±3.13)mm](F=12.891,P=0.000),and TMD-DDwR group[(7.12±3.69)mm](χ²=5.314,P=0.031). Conclusion This study confirmed that the contraction of LPM decreased in patients with TMD-DDwoR,which provided imaging evidence for the study of disc displacement mechanism in TMD patients.

PMID:34494529 | DOI:10.3881/j.issn.1000-503X.13076

Prog Urol. 2021 Sep 4:S1166-7087(21)00251-7. doi: 10.1016/j.purol.2021.07.011. Online ahead of print.

ABSTRACT

CONTEXT: The PP Convergences criteria group together 10 of the most significant clinical criteria for sensitization in the context of chronic pelvic pain. They are the result of a consensus of experts and represent to date the only clinical evaluation guide to identify patients with pelvic perineal pain in whom a pelvic sensitization component can be evoked.

OBJECTIVE: This work concerns the psychometric validation of these criteria. The aim is to answer 3 questions: 1) is the instrument reliable (i.e., sensitive, specific and accurate)?; 2) can we define a screening score for pelvic-perineal pain by sensitization from the CPP criteria?; 3) can combinations of criteria be defined to predict pelvic-perineal sensitization from the CPP criteria?

METHODOLOGY AND SUBJECTS: In total, 308 patients with pelviperineal pain were recruited during their medical consultation.

PROCEDURE: Fifteen expert physicians were asked to judge the presence or absence of the 10 CPP criteria and to make a diagnosis of the presence or absence of pelviperineal sensitization in their patient.

RESULTS: ROC curve analysis indicated that a score of 5 was the closest to a perfect score with a sensitivity of 95% and a specificity of 87%. They also indicate that the CPP criteria have a very good sensitivity (97%) and specificity (91%) and present globally a good reproducibility on all the criteria (Kappa>0.6). Finally, the statistical analyses reveal that the most discriminating criterion for predicting sensitization is Q8 (pain persisting after sexual activity).

CONCLUSION: The CPP criteria represent a very good screening tool for pelvic sensitization. The score of 5 corresponds to the score at which the patient has sufficient clinical criteria to be classified as sensitized.

LEVEL OF EVIDENCE: 4.

PMID:34493442 | DOI:10.1016/j.purol.2021.07.011

Clin Lymphoma Myeloma Leuk. 2021 Aug 12:S2152-2650(21)00328-1. doi: 10.1016/j.clml.2021.08.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016.

METHODS: Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas.

RESULTS: During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma.

CONCLUSION: These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.

PMID:34493476 | DOI:10.1016/j.clml.2021.08.002

Eur Urol. 2021 Sep 4:S0302-2838(21)01933-3. doi: 10.1016/j.eururo.2021.08.001. Online ahead of print.

ABSTRACT

BACKGROUND: Predict Prostate is a freely available online personalised risk communication tool for men with nonmetastatic prostate cancer. Its accuracy has been assessed in multiple validation studies, but its clinical impact among patients has not hitherto been assessed.

OBJECTIVE: To assess the impact of the tool on patient decision-making and disease perception.

DESIGN, SETTING, AND PARTICIPANTS: A multicentre randomised controlled trial was performed across eight UK centres among newly diagnosed men considering either active surveillance or radical treatment. A total of 145 patients were included between 2018 and 2020, with median age 67 yr (interquartile range [IQR] 61-72) and prostate-specific antigen 6.8 ng/ml (IQR 5.1-8.8).

INTERVENTION: Participants were randomised to either standard of care (SOC) information or SOC and a structured presentation of the Predict Prostate tool.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Validated questionnaires were completed by assessing the impact of the tool on decisional conflict, uncertainty, anxiety, and perception of survival.

RESULTS AND LIMITATIONS: Mean Decisional Conflict Scale scores were 26% lower in the Predict Prostate group (mean = 16.1) than in the SOC group (mean = 21.7; p = 0.027). Scores on the “support”, “uncertainty”, and “value clarity” subscales all favoured Predict Prostate (all p < 0.05). There was no significant difference in anxiety scores or final treatment selection between the two groups. Patient perception of 15-yr prostate cancer-specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower and more accurate among men in the Predict Prostate group (p < 0.001). In total, 57% of men reported that the Predict Prostate estimates for PCSM were lower than expected, and 36% reported being less likely to select radical treatment. Over 90% of patients in the intervention group found it useful and 94% would recommend it to others.

CONCLUSIONS: Predict Prostate reduces decisional conflict and uncertainty, and shifts patient perception around prognosis to be more realistic. This randomised trial demonstrates that Predict Prostate can directly inform the complex decision-making process in prostate cancer and is felt to be useful by patients. Future larger trials are warranted to test its impact upon final treatment decisions.

PATIENT SUMMARY: In this national study, we assessed the impact of an individualised risk communication tool, called Predict Prostate, on patient decision-making after a diagnosis of localised prostate cancer. Men were randomly assigned to two groups, which received either standard counselling and information, or this in addition to a structured presentation of the Predict Prostate tool. Men who saw the tool were less conflicted and uncertain in their decision-making, and recommended the tool highly. Those who saw the tool had more realistic perception about their long-term survival and the potential impact of treatment upon this.

TAKE HOME MESSAGE: The use of an individualised risk communication tool, such as Predict Prostate, reduces patient decisional conflict and uncertainty when deciding about treatment for nonmetastatic prostate cancer. The tool leads to more realistic perceptions about survival outcomes and prognosis.

PMID:34493413 | DOI:10.1016/j.eururo.2021.08.001

Eur Urol. 2021 Sep 4:S0302-2838(21)01979-5. doi: 10.1016/j.eururo.2021.08.011. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor monotherapy in metastatic castration-resistant prostate cancer (mCRPC) has produced modest results. High-dose radiotherapy may be synergistic with checkpoint inhibitors.

OBJECTIVE: To evaluate the efficacy and safety of the PD-L1 inhibitor avelumab with stereotactic ablative body radiotherapy (SABR) in mCRPC.

DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to July 2019, this prospective phase 2 study enrolled 31 men with progressive mCRPC after at least one prior androgen receptor-directed therapy. Median follow-up was 18.0 mo.

INTERVENTION: Avelumab 10 mg/kg intravenously every 2 wk for 24 wk (12 cycles). A single fraction of SABR (20 Gy) was administered to one or two disease sites within 5 d before the first and second avelumab treatments.

OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the disease control rate (DCR), defined as a confirmed complete or partial response of any duration, or stable disease/non-complete response/non-progressive disease for ≥6 mo (Prostate Cancer Clinical Trials Working Group 3-modified Response Evaluation Criteria in Solid Tumours version 1.1). Secondary endpoints were the objective response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS), and safety. DCR and ORR were calculated using the Clopper-Pearson exact binomial method.

RESULTS AND LIMITATIONS: Thirty-one evaluable men were enrolled (median age 71 yr, 71% with ≥2 prior mCRPC therapy lines, 81% with >5 total metastases). The DCR was 48% (15/31; 95% confidence interval [CI] 30-67%) and ORR was 31% (five of 16; 95% CI 11-59%). The ORR in nonirradiated lesions was 33% (four of 12; 95% CI 10-65%). Median rPFS was 8.4 mo (95% CI 4.5-not reached [NR]) and median OS was 14.1 mo (95% CI 8.9-NR). Grade 3-4 treatment-related adverse events occurred in six patients (16%), with three (10%) requiring high-dose corticosteroid therapy. Plasma androgen receptor alterations were associated with lower DCR (22% vs 71%, p = 0.13; Fisher’s exact test). Limitations include the small sample size and the absence of a control arm.

CONCLUSIONS: Avelumab with SABR demonstrated encouraging activity and acceptable toxicity in treatment-refractory mCRPC. This combination warrants further investigation.

PATIENT SUMMARY: In this study of men with advanced and heavily pretreated prostate cancer, combining stereotactic radiotherapy with avelumab immunotherapy was safe and resulted in nearly half of patients experiencing cancer control for 6 months or longer. Stereotactic radiotherapy may potentially improve the effectiveness of immunotherapy in prostate cancer.

PMID:34493414 | DOI:10.1016/j.eururo.2021.08.011

Semin Arthritis Rheum. 2021 Aug 20:S0049-0172(21)00155-4. doi: 10.1016/j.semarthrit.2021.08.001. Online ahead of print.

ABSTRACT

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group’s vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD).

METHODS: Patient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments’ face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument.

RESULTS: Forty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions.

CONCLUSION: The OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group’s vote; DLco was not endorsed.

PMID:34493396 | DOI:10.1016/j.semarthrit.2021.08.001

Rev Colomb Psiquiatr. 2021 Sep 4:S0034-7450(21)00129-3. doi: 10.1016/j.rcp.2021.06.006. Online ahead of print.

ABSTRACT

This research aims to determine the relationship between the variables adaptation to the disease, resilience and dispositional optimism in women with breast cancer in Montería (Colombia). This study is a descriptive-correlational type, evaluating 116 participants. The instruments applied were the Font Quality of Life Questionnaire, to assess the Index of Adaptation to Disease, Wagnild and Young’s Resilience Scale (RS) and the Life Orientation Test-Revised (LOT-R). The statistical program SPSS 25.0 was used for the analysis of the data. A normality test was performed which led to the application of the Spearman correlation coefficient. Findings indicated the presence of adaptation in the participants and resilient and optimistic characteristics, however, there is no significant relationship between these variables and adaptation to the disease.

PMID:34493398 | DOI:10.1016/j.rcp.2021.06.006

Psychol Med. 2021 Sep 8:1-14. doi: 10.1017/S0033291721002853. Online ahead of print.

ABSTRACT

BACKGROUND: It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general population is needed.

METHODS: Studies on individuals with FEP defined as drug-naïve (0 days exposure to antipsychotics) were included to conduct a systematic review. A meta-analysis of proportions for the prevalence of MetS in antipsychotic-naïve patients was performed. Prevalence estimates and 95% CI were calculated using a random-effect model. Subgroup analyses and meta-regressions to identify sources and the amount of heterogeneity were also conducted.

RESULTS: The search yielded 4143 articles. After the removal of duplicates, 2473 abstracts and titles were screened. At the full-text stage, 112 were screened, 18 articles were included in a systematic review and 13 articles in the main statistical analysis. The prevalence of MetS in naïve (0 days) FEP is 13.2% (95% CI 8.7-19.0). Ethnicity accounted for 3% of the heterogeneity between studies, and diagnostic criteria used for MetS accounted for 7%. When compared with controls matched by sex and age, the odds ratio is 2.52 (95% CI 1.29-5.07; p = 0.007).

CONCLUSIONS: Our findings of increased rates of MetS in naïve FEP patients suggest that we are underestimating cardiovascular risk in this population, especially in those of non-Caucasian origin. Our findings support that altered metabolic parameters in FEPs are not exclusively due to antipsychotic treatments.

PMID:34493353 | DOI:10.1017/S0033291721002853

J Acad Nutr Diet. 2021 Sep 3:S2212-2672(21)01040-6. doi: 10.1016/j.jand.2021.07.014. Online ahead of print.

ABSTRACT

BACKGROUND: Front-of-package (FOP) nutrition labeling systems differ in how they rate food and beverage products. There is a need to examine the implications of these differences, including their focus on nutrients of public health concern.

OBJECTIVE: Our aim was to examine the impacts of 4 common FOP labels on consumers’ purchases of products that received conflicting ratings across FOP systems.

DESIGN: In an experimental marketplace, participants were randomized to complete a series of purchases under 1 of 5 FOP conditions: no label, “high in” nutrient labels, multiple traffic light, Health Star Rating, or a 5-color nutrition grade.

PARTICIPANTS/SETTING: A final sample of 3,584 Canadians (13 years and older) were recruited from shopping centers in March to May 2018.

MAIN OUTCOME MEASURES: Probability of purchasing was assessed for 5 product categories (100% fruit juice, plain milk, chocolate milk, cheese snacks, and diet beverages), which received conflicting ratings across the FOP conditions.

STATISTICAL ANALYSES: Separate generalized linear mixed models estimated the influence of FOP condition on 5 binary outcomes (1 = purchased, 0 = not purchased) corresponding to the product categories.

RESULTS: Few differences were observed among the full sample. Among participants who noticed the labels (n = 1,993), those in the Health Star Rating condition were 4.5 percentage points (95% CI -7.0 to -1.9) more likely to purchase 100% fruit juice (compared to multiple traffic light) and 3.3 (95% CI 0.4 to 6.2) and 3.0 percentage points (95% CI 0.1 to 6.1) more likely to purchase cheese snacks (compared to no label and “high in”). “High in” labels produced fewer purchases of chocolate milk than no label.

CONCLUSIONS: Despite some similarities, existing FOP systems differ in the extent to which they promote or dissuade purchases of common product categories. Although the Health Star Rating might encourage purchases of products with certain positive nutritional attributes, “high in” and multiple traffic light systems might more effectively discourage purchases of products contributing nutrients of public health concern.

PMID:34493393 | DOI:10.1016/j.jand.2021.07.014