Nevin Manimala

JAMA Ophthalmol. 2023 Mar 23. doi: 10.1001/jamaophthalmol.2023.0302. Online ahead of print.

ABSTRACT

IMPORTANCE: The treatment of moderate to severe meibomian gland dysfunction (MGD) with oral doxycycline requires a 6-week course of treatment and has frequent adverse effects (AEs), which may be associated with poor compliance.

OBJECTIVE: To determine if the AEs of a 3-week course of oral azithromycin were equivalent to the AEs of a 6-week course of oral doxycycline.

DESIGN, SETTING, AND PARTICIPANTS: This double-masked randomized clinical trial was conducted at a referral center in Thailand from September 2018 to May 2022. Participants with moderate to severe MGD judged unresponsive to conservative management were included.

INTERVENTIONS: Patients were randomized 1:1 to receive oral azithromycin (1 g once per week for 3 weeks) or oral doxycycline (200 mg daily for 6 weeks).

MAIN OUTCOMES AND MEASURES: After initiating therapy, the study team assessed the total MGD score and Ocular Surface Disease Index (OSDI) score at the initial visit, at 6 weeks, and at 8 weeks, and assessed AEs at 6 weeks and 8 weeks. The prespecified equivalence margins for MGD score and OSDI score were set at ±2 and ±9, respectively.

RESULTS: A total of 137 eyes from 137 patients were randomized into groups, 68 eyes in the azithromycin group and 69 eyes in the doxycycline group (female, 66.4%; mean age, 62.0 [SD, 15.1] years). The adjusted mean difference of total MGD scores between groups at week 6 and week 8 were -0.33 (95% CI, -1.70 to 1.03; P for equivalence = .01) and 0.13 (95% CI, -1.59 to 1.84; P for equivalence = .02), respectively. The adjusted mean difference of OSDI between groups score at week 6 and week 8 was -1.20 (95% CI, -5.31 to 2.91; P for equivalence < .001) and -1.59 (95% CI, -5.73 to 2.55; P for equivalence < .001), respectively. In addition, patients treated with azithromycin had fewer gastrointestinal AEs (4.4% vs 15.9%; risk difference, 11.5%; 95% CI 1.6%-21.4%; P = .03).

CONCLUSIONS AND RELEVANCE: These data support an equivalency of effects of azithromycin as compared with doxycycline for MGD score and OSDI score at both follow-up times. The study did not show more gastrointestinal AEs in the azithromycin group. The reduced dosing and potentially fewer gastrointestinal AEs associated with azithromycin support its use as an alternative to doxycycline for at least 6 weeks.

TRIAL REGISTRATION: ThaiClinicalTrials.org Identifier: TCTR20180810001.

PMID:36951835 | DOI:10.1001/jamaophthalmol.2023.0302

J Urol. 2023 Mar 9:101097JU0000000000003396. doi: 10.1097/JU.0000000000003396. Online ahead of print.

ABSTRACT

PURPOSE: Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes.

MATERIALS AND METHODS: Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression.

RESULTS: Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome (family history of hereditary cancer syndrome). Family history of prostate cancer alone was not associated with biopsy progression, whereas family history of hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history of hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence.

CONCLUSIONS: An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

PMID:36951811 | DOI:10.1097/JU.0000000000003396

Euro Surveill. 2023 Mar;28(12). doi: 10.2807/1560-7917.ES.2023.28.12.2200408.

ABSTRACT

BackgroundThe exact epidemiology of tick-borne encephalitis virus (TBEV) infections is unknown because many TBEV infections have an influenza-like or asymptomatic course. Surveillance data are based on patients with any (predominantly neurological) symptoms that prompted diagnostic testing. Infection- and vaccine-induced antibodies against TBEV can be distinguished using an NS1 IgG ELISA.AimIn a seroprevalence study we aimed to investigate TBEV antibody prevalence, incidences, manifestation indices and potential protection rates in a highly endemic district in south-western Germany.MethodsWe analysed 2,220 samples from healthy blood donors collected between May and September 2021. The reported number of TBEV infections was provided on a sub-district level by the local public health authorities. Blood samples were first screened using a TBEV IgG ELISA. In a second step, all positive samples were further analysed with a recently established NS1 IgG ELISA. The presence of specific antibodies against TBEV (excluding cross-reacting antibodies against other flaviviruses) was confirmed by testing screening-positive samples with a microneutralisation assay.ResultsOf 2,220 included samples, 1,257 (57%) tested positive by TBEV IgG ELISA and 125 tested positive for infection-induced TBEV NS1 antibodies, resulting in a TBEV NS1 IgG seroprevalence at 5.6% in our population. The yearly incidence based on the NS1 ELISA findings resulted in 283 cases per 100,000 inhabitants.ConclusionUsing the TBEV NS1 IgG assay, we confirmed a manifestation index of ca 2% and a high incidence of predominantly silent TBEV infections (> 250/100,000/year), which exceeds the incidence of notified cases (4.7/100,000/year) considerably.

PMID:36951789 | DOI:10.2807/1560-7917.ES.2023.28.12.2200408

J Org Chem. 2023 Mar 23. doi: 10.1021/acs.joc.2c02771. Online ahead of print.

ABSTRACT

Within the scope of developing a new route to an active pharmaceutical ingredient intermediate, we had need of a fluorinated indazole. Although an established route was in place, it was undesirable due to safety and selectivity concerns. A concise and improved route was developed to form the desired indazole, which takes advantage of an electronically directed metalation/formylation sequence followed by condensation with methyl hydrazine to form a hydrazone and culminates in a copper-catalyzed intramolecular Ullmann cyclization. The Ullmann reaction was plagued with difficulties ranging from poor reactivity to thermal hazard concerns, but use of high-throughput screening, statistical modeling, and an unusual isolation method for fine chemicals, safe and optimal conditions were found that produce high-purity isolated material in excellent yields at a laboratory scale.

PMID:36951763 | DOI:10.1021/acs.joc.2c02771

Coron Artery Dis. 2023 Mar 1. doi: 10.1097/MCA.0000000000001227. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to determine whether a high level of high-sensitivity troponin T (hsTnT) predicts a positive treadmill test in patients with suspected stable ischemic heart disease (SIHD).

METHODS: In all, 366 patients with suspected SIHD were included in the study. We measured the serum hsTnT levels before the treadmill test. The treadmill test was performed according to the Bruce protocol.

RESULTS: Of the 366 patients, 97 had positive treadmill tests. The hsTnT levels were significantly higher in the positive group than in the negative group. In the binary logistic regression analysis, hsTnT, pretest probability, metabolic equivalents (METs), target heart rate (THR) percentage, and Duke treadmill score (DTS) were independent predictors of a positive treadmill test [hsTnT odds ratio (OR): 2.178, P < 0.001; pretest probability OR: 1.036, P = 0.007; METs OR: 0.755, P = 0.008; THR OR: 0.773, P < 0.001; DTS OR: 2.661, P = 0.012]. In the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) value of the model with the combined parameters of hsTnT, pretest probability, METs, THR, and DTS was statistically significant in predicting a positive treadmill test [combined model AUC: 0.945 (0.922-0.968), P < 0.001].

CONCLUSIONS: In sum, high pretest hsTnT levels predicted a positive treadmill test in patients with suspected SIHD. Analysis of the hsTnT levels before the treadmill test can increase the sensitivity and specificity of the treadmill test. The methods for measuring hsTnT levels are cheap and easily accessible and can be used before the treadmill test in patients with suspected SIHD.

PMID:36951749 | DOI:10.1097/MCA.0000000000001227

J Exp Psychol Gen. 2023 Mar 23. doi: 10.1037/xge0001372. Online ahead of print.

ABSTRACT

The Appraisal-Tendency Framework outlines that discrete emotions of similar valence behave differently, based on each emotion’s specific appraisal profile. In the domain of pricing decisions, a seminal paper by Lerner and colleagues report incidental, negative emotions of disgust and sadness to show a divergent effect on spending decisions based on the perceived ownership of a commodity. Specifically, disgust-reduced spending while sadness increased spending on a new product. However, these researchers theorized, but did not statistically test the effects of emotion-induced motivational goals for sadness (“change circumstances”) and disgust (“expel and avoid”) as the drivers behind their divergent effects on spending. This study (N = 403) sought to replicate these primary findings in close adherence to the original protocol with better measurement properties in a different geographical location. It further extended the examination by empirically testing the distinct mediating processes for sadness and disgust by utilizing measures identified from a pilot study (N = 169) based on the original protocol. We found support for the effect of sadness (vs. disgust and neutral) in inducing higher choice prices through the motivational goal of changing circumstances, but the expected pattern of results for disgust was not replicated. Additionally, we examined the role of arousal in this context as a factor driving the effect of these emotions on spending. Our research offers new insights regarding the well-known “misery-is not miserly” effect for practitioners while also providing impetus for future research on the endowment effect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:36951743 | DOI:10.1037/xge0001372

Haematologica. 2023 Mar 23. doi: 10.3324/haematol.2022.281876. Online ahead of print.

ABSTRACT

Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, GVHD and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 conventional situations: i) upfront Allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) Allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GVHD, extensive chronic GVHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late Allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (HR: 4.08, 95% CI [1.41-11.83], p=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR: 1.04, 95% CI [1.02-1.06], p.

PMID:36951165 | DOI:10.3324/haematol.2022.281876

Immunotherapy. 2023 Mar 23. doi: 10.2217/imt-2022-0145. Online ahead of print.

ABSTRACT

Aim: Comprehensively characterize the cardiotoxicity of CD19-directed chimeric antigen receptor T-cell (CAR-T) products. Materials & methods: Data between 2017 and 2021 in the US FDA’s Adverse Event Reporting System database were utilized. Disproportionality was measured using reporting odds ratio and information component. Hierarchical clustering analysis was performed to explore the relationships among cardiac events. Results: Tisagenlecleucel exhibited the highest percentage of death (53.24%) and life-threatening (13.39%) outcomes. Axicabtagene ciloleucel and tisagenlecleucel were equal in the number of positive signals (n = 15), while the former had excessive reporting of several cardiac events versus the latter, such as atrial fibrillation, cardiomyopathy, cardiorenal syndrome and sinus bradycardia. Conclusion: Several cardiac risks should be considered for CAR-T treatment and these events might vary in frequency and severity following different CAR-T agents.

PMID:36951157 | DOI:10.2217/imt-2022-0145

Musculoskeletal Care. 2023 Mar 23. doi: 10.1002/msc.1762. Online ahead of print.

ABSTRACT

OBJECTIVES: The primary aim was to investigate the effect of prefabricated foot orthoses on pain and function in people with chronic nonspecific low back pain (LBP). Secondary aims were to report on the recruitment rate, adherence to and safety of these interventions, and the relationship between physical activity and pain and function.

DESIGN: A two-arm parallel group (intervention vs. control) randomised (1:1) controlled trial.

SUBJECTS: Forty-one participants with chronic nonspecific LBP.

INTERVENTION: Twenty participants were randomised to the intervention group (prefabricated foot orthotic and The Back Book) and 21 to the control group (The Back Book). The primary outcomes for this study were change in pain and function from baseline to 12 weeks.

RESULTS: No statistically significant difference in pain was found between the intervention and control group (adjusted mean difference -0.84, 95% CI: -2.09 to 0.41, p = 0.18) at the 12-week follow-up. No statistically significant difference in function was found between the intervention and control group (adjusted mean difference -1.47, 95% CI: -5.51 to 2.57, p = 0.47) at the 12-week follow-up.

CONCLUSION: This study found no evidence of a significant beneficial effect of prefabricated foot orthoses for chronic nonspecific LBP. This study demonstrated that the rate of recruitment, intervention adherence and safety, and participant retention is acceptable and supportive of conducting a larger randomised controlled trial. Australian and New Zealand Clinical Trials Registry (ACTRN12618001298202).

PMID:36951154 | DOI:10.1002/msc.1762

J Prosthodont. 2023 Mar 23. doi: 10.1111/jopr.13680. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the distribution of marginal excess cement in vented and non-vented crowns and evaluate the effect of clinical cleaning procedures on the reduction of excess cement.

MATERIALS AND METHODS: Forty models with implant analogs in the position of the right maxillary first molar were divided into 4 groups (n = 10/group, vented/non-vented crowns with or without cleaning procedures). The abutment finish lines were placed 1 mm below the artificial gingiva buccally, mesially, and distally and at the gingival level palatally. A standardized amount (20 mg) of resin cement was applied in a thin layer to the intaglio surface of zirconia vented and non-vented crowns. The excess cement was removed by a dental explorer in groups with cleaning procedures. The distribution (area and depth) of the marginal excess cement was measured at each quadrant (buccal, mesial, palatal and distal) for all study samples. The data were analyzed using descriptive and analytical statistics (ɑ = 0.05).

RESULTS: The area and depth of the excess cement in each quadrant in the vented group was significantly smaller than that in the non-vented group, both with and without cleaning (p < 0.001). Cleaning procedures significantly reduced the area of excess cement in both vented and non-vented groups (all, p < 0.001 except for p < 0.05 at the buccal aspect of the vented group). The depth of excess cement in the vented group was significantly decreased with cleaning in the buccal quadrant compared with that without cleaning (p < 0.01). However, the depth of excess cement of the non-vented group was significantly increased with cleaning in all quadrants compared with that without cleaning (all, p<0.001 except for p < 0.05 at the distal aspect).

CONCLUSIONS: Crown venting significantly reduced the area and depth of the marginal excess cement in vitro. Cleaning procedure with a dental explorer significantly reduced the area of marginal excess cement in vitro, however, the excess cement can be pushed deeper in the non-vented group. This article is protected by copyright. All rights reserved.

PMID:36951153 | DOI:10.1111/jopr.13680