Nevin Manimala

JMIR Form Res. 2022 Jun 13;6(6):e35194. doi: 10.2196/35194.

ABSTRACT

BACKGROUND: Chronic pain is associated with an elevated risk of suicidal ideation (SI).

OBJECTIVE: We aimed to examine if the presence or the search for Meaning in Life (MiL) are associated with less SI and explore whether MiL profiles emerge in our cohort. These profiles can be described as high presence-high search, high presence-low search, low presence-low search, and low presence-high search.

METHODS: In this observational study, we recruited 70 patients who were referred to the Multidisciplinary Pain Center of the Geneva University Hospitals and who answered positively to question 9 on the Beck Depression Inventory, 2nd Edition, investigating SI. Patients who agreed to participate in the study were further investigated; they participated in a structured diagnostic interview to screen for psychiatric diagnoses. During this interview, they completed the Meaning in Life Questionnaire and the semistructured Scale for Suicide Ideation (SSI) to assess the characteristics and severity of SI.

RESULTS: There was a statistically significant correlation between the presence of MiL subscale and the SSI. These 2 scales had a negative and statistically highly significant correlation (R=-.667; P<.001). The results also showed a negative and statistically highly significant correlation between the score of the search for MiL and the SSI (R=-.456; P<.001). The results thus pointed to the presence of MiL as a potential protective factor against the severity of SI, while the search for MiL is also a possible resiliency factor, although to a lesser extent. The profile low presence-low search grouped the vast majority (47%) of the patients; in these patients, the mean SSI score was 14.36 (SD 5.86), much higher compared with that of the other subgroups.

CONCLUSIONS: This study’s results point to MiL as a concept of interest regarding devising psychotherapeutic interventions for chronic pain patients in order to reduce the suicidal risk and more accurately determine patients’ suffering.

PMID:35699974 | DOI:10.2196/35194

Leuk Lymphoma. 2022 Jun 14:1-10. doi: 10.1080/10428194.2022.2087069. Online ahead of print.

ABSTRACT

Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients: 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6; p < 0.001 and HR = 4.23; p = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.

PMID:35699970 | DOI:10.1080/10428194.2022.2087069

JAMA Netw Open. 2022 Jun 1;5(6):e2216958. doi: 10.1001/jamanetworkopen.2022.16958.

ABSTRACT

IMPORTANCE: Breast cancer causes disproportionate disease burden among various racial and ethnic groups in the US. However, state-level temporal trends and racial and ethnic disparities and whether metabolic and lifestyle factors and screening access are associated with temporal changes remain largely unknown.

OBJECTIVES: To investigate temporal trends and racial and ethnic variations at the state level and ecological correlations between obesity, physical activity, and mammography screening and breast cancer incidence and mortality trends among women in the US.

DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted to analyze breast cancer incidence and mortality trends among women in the US from January 1, 1999, to December 31, 2017, whereas an ecological analysis was performed to assess the associations. Data were analyzed from March 1, 2021, to September 30, 2021. Population-based cancer registry data were obtained from US Cancer Statistics incidence and mortality data. Prevalence of obesity, physical activity, and mammography screening were obtained from the Behavioral Risk Factor Surveillance System.

EXPOSURES: Prevalence of obesity, physical activity, and mammography screening.

MAIN OUTCOMES AND MEASURES: Breast cancer incidence and mortality trends from 1999 to 2017 in the 50 US states and the District of Columbia.

RESULTS: A total of 4 136 123 breast cancer cases and 782 454 deaths were included in the analysis, with a significant reduction in incidence (average annual percent change [AAPC], -0.4% [95% CI, -0.6% to -0.2%)]) and mortality (AAPC, -1.7% [95% CI, -1.8% to -1.5%]) during the study period. A significant state-level variation in breast cancer incidence and mortality between White women and those of other races and ethnicities was observed. A significant positive correlation was found between obesity and breast cancer incidence (r = 0.316; P = .02) and mortality (r = 0.400; P = .004) and an inverse correlation was found between physical activity and incidence (r = -0.577; P < .001) in women 55 years or older and mammography screening and mortality trends (r = -0.644; P < .001) in women 40 years or older.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that racial and ethnic disparities exist at the state level with regard to breast cancer incidence and mortality among women in the US. Metabolic and lifestyle factors and screening access were associated with the observed trends and racial and ethnic disparities. Interventions targeting these factors may help reduce the incidence of breast cancer and related deaths.

PMID:35699957 | DOI:10.1001/jamanetworkopen.2022.16958

Ther Innov Regul Sci. 2022 Jun 14. doi: 10.1007/s43441-022-00420-1. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: DARE-19 (NCT04350593) was a randomized trial studying the effects of dapagliflozin, an SGLT2 inhibitor, in hospitalized patients with COVID-19 pneumonia and cardiometabolic risk factors. The conduct of DARE-19 offered the opportunity to define an innovative and clinically meaningful endpoint in a new disease that would best reflect the known profile of dapagliflozin, accompanied by the statistical challenges of analysis and interpretation of such a novel endpoint.

METHODS: Hierarchical composite endpoints (HCEs) are based on clinical outcomes which, unlike traditional composite endpoints incorporate ranking of components according to clinical importance. Design of an HCE requires the clinical considerations specific to the therapeutic area under study and the mechanism of action of the investigational treatment. Statistical aspects for the clinical endpoints include the proper definition of the estimand as suggested by ICH E9(R1) for the precise specification of the treatment effect measured by an HCE.

RESULTS: We describe the estimand of the DARE-19 trial, where an HCE was constructed to capture the treatment effect of dapagliflozin in hospitalized patients with COVID-19, and was analyzed using a win odds. Practical aspects of designing new studies based on an HCE are described. These include sample size, power, and minimal detectable effect calculations for an HCE based on the win odds analysis, as well as handling of missing data and the clinical interpretability of the win odds in relation to the estimand.

CONCLUSIONS: HCEs are flexible endpoints that can be adapted for use in different therapeutic areas, with win odds as the analysis method. DARE-19 is an example of a COVID-19 trial with an HCE as one of the primary endpoints for estimating a clinically interpretable treatment effect in the COVID-19 setting.

PMID:35699910 | DOI:10.1007/s43441-022-00420-1

Hepatol Int. 2022 Jun 14. doi: 10.1007/s12072-022-10357-0. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive.

METHODS: An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method.

RESULTS: Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016-1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032-8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients.

CONCLUSIONS: ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.

PMID:35699864 | DOI:10.1007/s12072-022-10357-0

Adv Exp Med Biol. 2022 Jun 15. doi: 10.1007/5584_2022_722. Online ahead of print.

ABSTRACT

The availability of virucidal compounds to reduce the impact of respiratory viruses is a relevant topic for public health, especially during the recent coronavirus disease (COVID-19) pandemic. Antimicrobial properties of Xibornol are known since the 1970s, but its activity on viruses is currently little explored. In this study, Xibornol activity at a fixed concentration of 0.03 mg/100 ml has been evaluated on five respiratory viruses (Human Adenovirus 5, Human Rhinovirus type 13, Human Coronavirus 229E, Human Parainfluenza Virus type 1, and Human Respiratory Syncytial Virus) through in vitro experiments based on adapted European standard UNI EN 14476-20019. The experiments were carried out under two different environmental conditions, one with the addition of fetal bovine serum to simulate an in vivo condition (dirty condition) and the other without the addition of any organic substances (clean condition). The viral abatement of Xibornol (expressed as Log₁₀ reduction – LR) was statistically significant under both clean and dirty environmental conditions. Namely, in clean condition, LR ranged from 2.67 to 3.84, while in the dirty one the abatement was slightly lower (from 1.75 to 3.03). Parainfluenza Virus and Human Adenovirus were most resistant compared to the other viruses. The obtained data confirmed Xibornol activity and its use as topic substance for viral inactivation to prevent upper respiratory tract disease.

PMID:35699841 | DOI:10.1007/5584_2022_722

Aging Clin Exp Res. 2022 Jun 14. doi: 10.1007/s40520-022-02155-3. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB).

METHODS: The t-FAB (ranging 0-12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18-96 years; education range = 4-23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test-retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores.

RESULTS: In HPs, t-FAB measures yielded high inter-rater/test-retest reliability (ICC = .78-.94), were internally related (p ≤ .005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤ .0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds < .001). Education predicted all t-FAB scores (p < .001), whereas age only the t-FAB-M score (p ≤ .004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (r_s = .43-.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC = .73-.76).

DISCUSSION: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice.

PMID:35699839 | DOI:10.1007/s40520-022-02155-3

Eur Spine J. 2022 Jun 14. doi: 10.1007/s00586-022-07223-w. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether the open or the minimally invasive transforaminal lumbar interbody fusion (O-TLIF, MI-TLIF) is the favored treatment, we provide first meta-analyses using prospective studies with at least two years follow-up only and present the clinical relevance of statistical results for the first time.

METHODS: After a systematic review of six databases, we conducted 10 meta-analyses of randomized controlled trials (RCTs) and 10 meta-analyses of eligible prospective studies (EPSs) to compare fusion rate, patient-reported outcome measures (back pain (B-VAS), leg pain, Oswestry Disability Index (ODI)), for the first time safety outcome measures as operative and postoperative complications per case, and the perioperative outcome measures estimated blood loss (EBL), operation time and length of hospital stay (LOS). The clinical relevance was assessed by overall effect sizes (OESs) of statistically significant meta-analytic results.

RESULTS: In our meta-analyses of RCTs, MI-TLIF is statistically significantly superior in ODI, EBL and LOS, with clinically meaningful OESs only in EBL and LOS. In meta-analyses of EPSs, MI-TLIF is statistically significantly superior in B-VAS, postoperative complications per case, EBL and LOS, all with clinically meaningful OESs except for B-VAS. The meta-analyses of remaining outcome measures present statistically nonsignificant results. In a descriptive analysis of complications, postoperative wound infections predominate in O-TLIF and hardware malposition in MI-TLIF.

CONCLUSION: After at least two years, O-TLIF and MI-TLIF can be considered equally efficacious, which simplifies surgeons’ decision between both treatments, however, with the safety outcome measure postoperative complications per case and the perioperative outcome measures EBL and LOS in favor of MI-TLIF. LEVEL OF EVIDENCE I: Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias.

PMID:35699832 | DOI:10.1007/s00586-022-07223-w

J Clin Immunol. 2022 Jun 14. doi: 10.1007/s10875-022-01301-w. Online ahead of print.

ABSTRACT

PURPOSE: A recent phase II open-label study of the interleukin 1 (IL-1) receptor antagonist (IL-1Ra) anakinra in treating IVIG-resistant Kawasaki disease (KD) patients reported promising results. Here, we aimed to characterize the immunological impact of IL-1 blockade in this unique study population.

METHODS: Patients’ and control sera and supernatants of cells (whole blood, neutrophils, coronary artery endothelial cells) stimulated with recombinant IL-1β were analyzed for single or multiple marker (n = 22) expression by ELISA or multiplexed bead array assay. Data were analyzed using unsupervised hierarchical clustering, multiple correlation, and multi-comparison statistics and were compared to retrospective analyses of KD transcriptomics.

RESULTS: Inflammation in IVIG-resistant KD (n = 16) is hallmarked by over-expression of innate immune mediators (particularly IL-6 > CXCL10 > S100A12 > IL-1Ra). Those as well as levels of immune or endothelial cell activation markers (sICAM-1, sVCAM-1) declined most significantly in course of anakinra treatment. Prior as well as following IL-1R blockade, over-expression of leucine-rich-α2-glycoprotein 1 (LRG1) associated best with remnant inflammatory activity and the necessity to escalate anakinra dosage and separated inflammatory KD patients from sJIA-MAS (n = 13) and MIS-C (n = 4). Protein as well as retrospective gene expression analyses indicated tight association of LRG1 with IL-1β signaling and neutrophilia, while particularly neutrophil stimulation with recombinant IL-1β resulted in concentration-dependent LRG1 release.

CONCLUSION: Our study identifies LRG1 as known trigger of endothelial activation and cardiac re-modeling to associate with IL-1β signaling in KD. Besides a potential patho-mechanistic implication of these findings, our data suggest blood leukocyte and neutrophil counts to best predict response to IL-1Ra treatment in IVIG-resistant KD.

PMID:35699824 | DOI:10.1007/s10875-022-01301-w

Lasers Med Sci. 2022 Jun 14. doi: 10.1007/s10103-022-03589-x. Online ahead of print.

ABSTRACT

This study aims to compare the results of both CO₂ laser and diode laser combined arytenoidectomy with posterior cordectomy in managing patients with bilateral vocal fold paralysis. A prospective study involved 80 bilateral vocal cord immobility patients in adduction. They are divided into two groups according to the laser used, whether CO₂ (with a wavelength of 10.6 µm) or diode (with a wavelength of 980 nm). We used mMRC (Modified Medical Research Council) dyspnea scale to assess dyspnea in our patients, while the voice was evaluated by both maximum phonation time and the voice handicap index. Quantitative variables were described using means and standard deviations, while categorical variables were described using frequencies and were compared using the chi-square test, Fisher exact test, and Monte Carlo test. There was a statistically non-significant difference between the studied groups regarding mMRC dyspnea scale and Voice Handicap Index preoperatively and postoperatively. There is a statistically significant difference between the two groups regarding maximum phonation time postoperatively (significantly higher in the CO₂ laser group) (p < 0.001). The CO₂ laser and diode laser could be used safely for the management of bilateral vocal cord paralysis. The CO₂ laser maintains better voice parameters and less postoperative pain, while the diode laser gives less operative time, lower cost, and simplicity of use.

PMID:35699806 | DOI:10.1007/s10103-022-03589-x