Category: Nevin Manimala

JAMA Netw Open. 2023 Jul 3;6(7):e2323112. doi: 10.1001/jamanetworkopen.2023.23112.

ABSTRACT

IMPORTANCE: It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.

OBJECTIVE: To assess the clinical characteristics and outcomes of patients with C acnes endocarditis.

DESIGN, SETTING, AND PARTICIPANTS: A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022.

MAIN OUTCOMES AND MEASURES: Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates.

RESULTS: A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%]).

CONCLUSIONS AND RELEVANCE: This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence.

PMID:37436747 | DOI:10.1001/jamanetworkopen.2023.23112

JAMA Netw Open. 2023 Jul 3;6(7):e2323115. doi: 10.1001/jamanetworkopen.2023.23115.

ABSTRACT

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors.

OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 years after their initial diagnosis (ie, long-term survivors of cancer). Statistical analysis was conducted from November 2022 to January 2023.

MAIN OUTCOMES AND MEASURES: Survival time ratios (TRs) were calculated using accelerated failure time models, and the primary outcome of interest examined was death from index cancer vs alternative (nonindex cancer) mortality across breast, prostate, colon, and rectal cancer cohorts. Secondary outcomes included subgroup mortality in cancer-specific risk groups, categorized based on prognostic factors, and proportion of deaths due to cancer-specific vs noncancer-specific causes. Independent variables included age, sex, race and ethnicity, income, residence, stage, grade, estrogen receptor status, progesterone receptor status, prostate-specific antigen level, and Gleason score. Follow-up ended in 2019.

RESULTS: The study included 627 702 patients (mean [SD] age, 61.1 [12.3] years; 434 848 women [69.3%]): 364 230 with breast cancer, 118 839 with prostate cancer, and 144 633 with colorectal cancer who survived 5 years or more from an initial diagnosis of early-stage cancer. Factors associated with shorter median cancer-specific survival included stage III disease for breast cancer (TR, 0.54; 95% CI, 0.53-0.55) and colorectal cancer (colon: TR, 0.60; 95% CI, 0.58-0.62; rectal: TR, 0.71; 95% CI, 0.69-0.74), as well as a Gleason score of 8 or higher for prostate cancer (TR, 0.61; 95% CI, 0.58-0.63). For all cancer cohorts, patients at low risk had at least a 3-fold higher noncancer-specific mortality compared with cancer-specific mortality at 10 years of diagnosis. Patients at high risk had a higher cumulative incidence of cancer-specific mortality than noncancer-specific mortality in all cancer cohorts except prostate.

CONCLUSIONS AND RELEVANCE: This study is the first to date to examine competing oncologic and nononcologic risks focusing on long-term adult survivors of cancer. Knowledge of the relative risks facing long-term survivors may help provide pragmatic guidance to patients and clinicians regarding the importance of ongoing primary and oncologic-focused care.

PMID:37436746 | DOI:10.1001/jamanetworkopen.2023.23115

JAMA Psychiatry. 2023 Jul 12. doi: 10.1001/jamapsychiatry.2023.2206. Online ahead of print.

ABSTRACT

IMPORTANCE: Few studies have estimated the lifetime incidence of mental health disorders and the association with socioeconomic functioning.

OBJECTIVE: To investigate whether the lifetime incidence of treated mental health disorders is substantially higher than previously reported and estimate associations with long-term socioeconomic difficulties.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based register linkage study includes a randomly selected sample of 1.5 million individuals from the population of Denmark from 1995 to 2018. Data were analyzed from May 2022 to March 2023.

MAIN OUTCOMES AND MEASURES: Lifetime incidence of any treated mental health disorder in the general population was estimated from birth to age 100 years taking into account the competing risk of all-cause death and associations with socioeconomic functioning. Register measures were (1) from hospitals, a diagnosis of any mental health disorder at an inpatient/outpatient hospital contact; (2) from hospitals and prescription statistics, any mental health disorder/psychotropic prescription, including a hospital-contact diagnosis, or any psychotropic medication prescribed by physicians, including general practitioners or private psychiatrists; and (3) socioeconomic functioning as indicated by highest educational achievement, employment, income, residential status, and marital status.

RESULTS: Among a sample of 462 864 individuals with any mental health disorder, the median (IQR) age was 36.6 years (21.0-53.6 years), 233 747 (50.5%) were male, and 229 117 (49.5%) were female. Of these, 112 641 were registered with a hospital-contact mental health disorder diagnosis and 422 080 with a prescription of psychotropic medication. The cumulative incidence of a hospital-contact mental health disorder diagnosis was 29.0% (95% CI, 28.8-29.1), 31.8% (95% CI, 31.6-32.0) for females, and 26.1% (95% CI, 25.9-26.3) for males. When also considering psychotropic prescriptions, the cumulative incidence of any mental health disorder/psychotropic prescription was 82.6% (95% CI, 82.4-82.6), 87.5% (95% CI, 87.4-87.7) for females, and 76.7% (95% CI, 76.5-76.8) for males. Socioeconomic difficulties were associated with mental health disorder/psychotropic prescriptions, including lower income (hazard ratio [HR], 1.55; 95% CI, 1.53-1.56), increased unemployment or disability benefit (HR, 2.50; 95% CI, 2.47-2.53), and a greater likelihood of living alone (HR, 1.78; 95% CI, 1.76-1.80) and being unmarried (HR, 2.02; 95% CI, 2.01-2.04) during long-term follow-up. These rates were confirmed in 4 sensitivity analyses with the lowest being 74.8% (95% CI, 74.7-75.0) (1) by using varying exclusion periods, (2) by excluding prescriptions of anxiolytics and quetiapine that may be used for off-label indications, (3) by defining any mental health disorder/psychotropic prescription as any hospital-contact mental health disorder diagnosis or any psychotropic medication prescribed at least 2 times, and (4) by excluding individuals with somatic diagnoses for which psychotropics may be prescribed off-label.

CONCLUSIONS AND RELEVANCE: This registry study of data from a large representative sample of the Danish population showed that the majority of individuals either received a diagnosis of a mental health disorder or were prescribed psychotropic medication during their lifetime, which was associated with subsequent socioeconomic difficulties. These findings may help change our understanding of normalcy and mental illness, reduce stigmatization, and further prompt rethinking the primary prevention of mental illness and future mental health clinical resources.

PMID:37436730 | DOI:10.1001/jamapsychiatry.2023.2206

JAMA Surg. 2023 Jul 12. doi: 10.1001/jamasurg.2023.2521. Online ahead of print.

ABSTRACT

IMPORTANCE: The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking.

OBJECTIVE: To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups.

EXPOSURE: Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery.

MAIN OUTCOME AND MEASURES: The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes.

RESULTS: Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group.

CONCLUSIONS AND RELEVANCE: Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

PMID:37436726 | DOI:10.1001/jamasurg.2023.2521

Percept Mot Skills. 2023 Jul 12:315125231189098. doi: 10.1177/00315125231189098. Online ahead of print.

ABSTRACT

In this study we investigated whether the accuracy of intraset repetitions in reserve (RIR) predictions changes over time. Nine trained men completed three bench press training sessions per week for 6 weeks (following a 1-week familiarization). The final set of each session was performed until momentary muscular failure, with participants verbally indicating their perceived 4RIR and 1RIR. RIR prediction errors were calculated as raw differences (RIRDIFF), with positive and negative values indicating directionality, and absolute RIRDIFF (absolute value of raw RIRDIFF) indicating error scores. We constructed mixed effect models with time (i.e., session) and proximity to failure as fixed effects, repetitions as a covariate, and random intercepts per participant to account for repeated measures, with statistical significance set at p ≤ .05. We observed a significant main effect for time on raw RIRDIFF (p < .001), with an estimated marginal slope of -.077 repetitions, indicating a slight decrease in raw RIRDIFF over time. Further, the estimated marginal slope of repetitions was -.404 repetitions, indicating a decrease in raw RIRDIFF as more repetitions were performed. There were no significant effects on absolute RIRDIFF. Thus, RIR rating accuracy did not significantly improve over time, though there was a greater tendency to underestimate RIR in later sessions and during higher repetition sets.

PMID:37436724 | DOI:10.1177/00315125231189098

J Natl Cancer Inst. 2023 Jul 12:djad137. doi: 10.1093/jnci/djad137. Online ahead of print.

ABSTRACT

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a four-criterion framework for assessing interactions which includes statistical, qualitative, biological, and practical approaches. Using ovarian cancer, we present the application of the framework as this is an important step in developing more accurate risk stratification models. Using data from nine case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions between 15 unequivocal risk/protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association between endometriosis, first degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.

PMID:37436712 | DOI:10.1093/jnci/djad137

J Periodontol. 2023 Jul 12. doi: 10.1002/JPER.23-0285. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate tooth-related factors that influence the reduction of pocket probing depths (PPD) after non-surgical periodontal therapy (NST).

MATERIALS AND METHODS: 746 patients with a total of 16825 teeth were included and retrospectively analyzed. PPD reduction after NST was correlated with the tooth-related factors; tooth type, number of roots, furcation involvement, vitality, mobility and type of restoration; using logistic multilevel regression for statistical analysis.

RESULTS: NST was able to reduce probing depth overall stratified probing depths (1.20±1.51mm p = <0.001). The reduction was significantly higher at teeth with higher probing depths at baseline. At pockets with PPD ≥ 6mm PPD remains high after NST. Tooth type, number of roots, furcation involvement, vitality, mobility and type of restoration are significantly and independently associated with the rate of pocket closure.

CONCLUSION: The tooth-related factors: tooth type, number of roots, furcation involvement, vitality, mobility and type of restoration had a significant and clinically relevant influence on phase I and II therapy. Considering these factors in advance may enhance the prediction of sites not responding adequately and the potential need for additional treatment, such as re-instrumentation or periodontal surgery, to ultimately achieve the therapy endpoints. This article is protected by copyright. All rights reserved.

PMID:37436696 | DOI:10.1002/JPER.23-0285

J Bone Miner Res. 2023 Jul 12. doi: 10.1002/jbmr.4880. Online ahead of print.

ABSTRACT

This study aims to evaluate the causal effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on bone mineral density (BMD), osteoporosis, and fracture risk using genetics. Two-sample Mendelian randomization (MR) analyses were performed utilizing two sets of genetic variants as instruments (six and two single-nucleotide polymorphisms [SNPs]) associated with SLC5A2 gene expression and glycated hemoglobin A1c levels. Summary statistics of BMD from the Genetic Factors for Osteoporosis (GEFOS) consortium (BMD for total body, n = 66,628; femoral neck, n = 32,735; lumbar spine, n = 28,498; forearm, n = 8,143) and osteoporosis (6,303 cases, 325,717 controls) and 13 types of fracture (≤ 17,690 cases, ≤ 328,382 controls) data from the FinnGen study were obtained. One-sample MR and genetic association analyses were conducted in UK Biobank using the individual-level data of heel BMD (n = 256,286) and incident osteoporosis (13,677 cases, 430,262 controls) and fracture (25,806 cases, 407,081 controls). Using six SNPs as the instrument, genetically proxied SGLT2 inhibition showed little evidence of association with BMD of total body, femoral neck, lumbar spine, and forearm (all P ≥ 0.077). Similar results were observed using two SNPs as instruments. Little evidence was found for the SGLT2 inhibition effect on osteoporosis (all P ≥ 0.112) or any 11 major types of fracture (all P ≥ 0.094), except for a nominal significance for fracture of lower leg (P = 0.049) and shoulder and upper arm (P = 0.029). One-sample MR and genetic association analysis showed that both the weighted genetic risk scores constructed from the six and two SNPs were not causally associated with heel BMD, osteoporosis, and fracture (all P ≥ 0.387). Therefore, this study does not support an effect of genetically proxied SGLT2 inhibition on fracture risk. This article is protected by copyright. All rights reserved.

PMID:37436694 | DOI:10.1002/jbmr.4880

J Periodontol. 2023 Jul 12. doi: 10.1002/JPER.23-0161. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence regarding the etiology behind bone loss around submerged, prosthetically non-loaded implants is still limited. The long-term stability and success of implants with early crestal bone loss (ECBL) especially when placed as two-stage implants, is uncertain. Hence, the aim of this retrospective study is to analyze the potential patient-level, tooth and implant related factors for ECBL around osseointegrated, submerged implants, prior to restoration as compared with healthy implants with no bone loss.

METHODS: Retrospective data was collected from patient electronic health records between 2015 and 2022. Control sites included healthy implants with no bone loss and test sites included implants with ECBL, both of which were submerged. Patient, tooth and implant level data was collected. ECBL was assessed using peri-apical radiographs obtained during implant placement and second-stage surgeries. Generalized estimating equation logistic regression models were used to account for multiple implants within patients.

RESULTS: The total number of implants included in the study was 200 from 120 patients. Lack of supportive periodontal therapy (SPT) was shown to have nearly five-times higher risk of developing ECBL and was statistically significant (p < 0.05). Guided bone regeneration (GBR) procedures prior to implant placement had a protective effect with an odds ratio of 0.29 (p < 0.05).

CONCLUSIONS: Lack of SPT was significantly associated with ECBL, while sites that received GBR procedures prior to implant placement were less likely to exhibit ECBL. Our results underscore the importance periodontal treatment and SPT for peri-implant health, even when the implants are submerged and unrestored. This article is protected by copyright. All rights reserved.

PMID:37436693 | DOI:10.1002/JPER.23-0161

Immunol Res. 2023 Jul 12. doi: 10.1007/s12026-023-09407-y. Online ahead of print.

ABSTRACT

An increasing number of breakthrough-COVID-19-vaccinated individuals are being reported across the world. Humoral immunity has a crucial role in combating infection. In this study, we aimed to assess the importance of anti-COVID-S1-IgA and anti-COVID-NP-IgA in confirmed COVID-19 after vaccination (breakthrough infection group). Blood samples were collected from the breakthrough infection group within one week of breakthrough infections (n = 34). A second sample was also collected after 4 to 8 weeks (n = 27). Blood samples of healthy individuals (n = 29) were collected 4-8 weeks after the completion of vaccination. Anti-COVID-S1-IgA and anti-COVID-NP-IgA were detected by ELISA. Statistical analysis was performed using IBM SPSS version 24. In this study, we found a higher positivity rate for anti-COVID-S1-IgA in the breakthrough infection group (70% vs. 28% in healthy individuals). Anti-COVID-NP-IgA was not found in the control group (11% in the breakthrough infection group vs. 0 in healthy individuals). In the breakthrough-infected group, the positivity rate of anti-COVID-NP-IgA decreased significantly (median titers 16.9 IU/ml decreased to 4.2 IU/ml) p = 0.001), while anti-COVID-S1-IgA increased over a period of 4-8 weeks (9.35-16.35 IU/ml). Importantly, IgA response to both COVID-19 NP and S1 antigens was not found in 13 patients at initial testing. The findings of this study show that serum IgA may have a role both in breakthrough infections and also in the prevention of severe infection. Sluggish anti-COVID-19-IgA antibody response may be responsible for the occurrence of COVID-19 infection in breakthrough infection. On the other hand, more sustained anti-COVID-19-S1-IgA over a longer period of time may have a role in preventing these patients from severe infections and hospitalization. However, a study on a larger sample size including patients with severe disease after vaccination is required to prove this hypothesis. To the best of our knowledge, this is the first study reporting the importance of serum IgA in breakthrough-infected patients from our region.

PMID:37436673 | DOI:10.1007/s12026-023-09407-y