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Nevin Manimala Statistics

Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia

JAMA Netw Open. 2023 Oct 2;6(10):e2338088. doi: 10.1001/jamanetworkopen.2023.38088.

ABSTRACT

IMPORTANCE: Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.

OBJECTIVE: To examine the association between adult ADHD and the risk of dementia.

DESIGN, SETTING, AND PARTICIPANTS: This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.

EXPOSURE: Adult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.

MAIN OUTCOME AND MEASURES: Cox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.

RESULTS: At the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.

PMID:37847497 | DOI:10.1001/jamanetworkopen.2023.38088

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A Spatiotemporal and Multisensory Approach to Designing Wearable Clinical ICU Alarms

J Med Syst. 2023 Oct 17;47(1):105. doi: 10.1007/s10916-023-01997-2.

ABSTRACT

In health care, auditory alarms are an important aspect of an informatics system that monitors patients and alerts clinicians attending to multiple concurrent tasks. However, the volume, design, and pervasiveness of existing Intensive Care Unit (ICU) alarms can make it difficult to quickly distinguish their meaning and importance. In this study, we evaluated the effectiveness of two design approaches not yet explored in a smartwatch-based alarm system designed for ICU use: (1) using audiovisual spatial colocalization and (2) adding haptic (i.e., touch) information. We compared the performance of 30 study participants using ICU smartwatch alarms containing auditory icons in two implementations of the audio modality: colocalized with the visual cue on the smartwatch’s low-quality speaker versus delivered from a higher quality speaker located two feet away from participants (like a stationary alarm bay situated near patients in the ICU). Additionally, we compared participant performance using alarms with two sensory modalities (visual and audio) against alarms with three sensory modalities (adding haptic cues). Participants were 10.1% (0.24s) faster at responding to alarms when auditory information was delivered from the smartwatch instead of the higher quality external speaker. Meanwhile, adding haptic information to alarms improved response times to alarms by 12.2% (0.23s) and response times on their primary task by 10.3% (0.08s). Participants rated learnability and ease of use higher for alarms with haptic information. These small but statistically significant improvements demonstrate that audiovisual colocalization and multisensory alarm design can improve user response times.

PMID:37847469 | DOI:10.1007/s10916-023-01997-2

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Evaluation of the international Ki67 working group cut point recommendations for early breast cancer: comparison with 21-gene assay results in a large integrated health care system

Breast Cancer Res Treat. 2023 Oct 17. doi: 10.1007/s10549-023-07118-4. Online ahead of print.

ABSTRACT

PURPOSE: The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay.

METHODS: We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics.

RESULTS: Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively.

CONCLUSION: The IKWG’s Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.

PMID:37847456 | DOI:10.1007/s10549-023-07118-4

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Prevalence of the virulence genes and their correlation with carbapenem resistance amongst the Pseudomonas aeruginosa strains isolated from a tertiary hospital in China

Antonie Van Leeuwenhoek. 2023 Oct 17. doi: 10.1007/s10482-023-01869-2. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is one of the top-listed pathogens in nosocomial infection. It is notorious for its complicated virulence system and rapid adaptability to drugs or antimicrobials. In this study, we aimed to evaluate the prevalence of sixteen virulence genes in four groups including type III secretion system, biofilm formation, extracellular toxin biosynthesis and enzymes amongst 209 clinical Pseudomonas aeruginosa strains. We investigated the different distribution patterns of virulence genotypes based on carbapenem-resistant phenotype or the carriage of carbapenemase genes. The detection rate of each virulence gene varied greatly. phzM and plcN were detected in all collected strains, while pilB and exoU were only carried by a small portion of isolates (6.7% and 16.3%). Additionally, the number of genotypes observed in each group of examined virulence genes ranged from 4 to 8. Only the distribution of genotypes of type III secretion system showed statistical difference between carbapenem-mediated or carbapenem-resistant and carbapenem-sensitive strains. The virulence genotype of Pseudomonas aeruginosa was possibly interrelated to its resistance mechanism. Further research suggested that one particular TTSS genotype exhibited higher ratio in carbapenemase-producing strains and exoS was less frequently detected in CRPA strains carrying carbapenemase gene. Generally, the significant genetic diversity of virulence genes amongst Pseudomonas aeruginosa strains was highlighted in this study. Specific TTSS genotypes were associated with carbapenem-resistance. In particular, certain incompatibility might exist between exoS and carbapenemase genes, which provided valuable information for further understanding the relationship between carbapenem resistance and virulence.

PMID:37847452 | DOI:10.1007/s10482-023-01869-2

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Nutritional status and its correlation to prognosis of nasopharyngeal carcinoma patients in different ages in China: a multicenter cohort study

Support Care Cancer. 2023 Oct 17;31(12):638. doi: 10.1007/s00520-023-08104-8.

ABSTRACT

Nasopharyngeal carcinoma (NPC) patients usually presented malnutrition under chemoradiotherapy (CRT)/radiotherapy (RT). Few studies stratified by age to investigate the association of nutritional status with overall survival (OS) in NPC patients. This study aimed to explore the nutritional parameters related prognosis of NPC patients in different age. The total 1365 NPC patients were classified into young (18~45), middle-aged (46~60), and old groups (> 60). PG-SGA scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and blood indicators (albumin, prealbumin, transferrin, C-reactive protein, hemoglobin, and total lymphocyte) were assessed. Cox regression analysis was performed to evaluate the association between risk factors of nutritional status and the overall survival in different age group of NPC patients. Kaplan-Meier (KM) survival analysis was used to estimate the effect of nutritional indexes on prognosis. The abnormal rate of albumin, prealbumin, hemoglobin, hand grip strength, and calf circumference increased with age. The malnutrition occurred in all age group and low calf circumference (HR, 4.427, 1.167-16.791) was an independent death risk in young adults. Distant metastasis (HR, 4.754, 2.737-8.260), low albumin (HR, 3.530, 1.708-7.296), hand grip strength (HR, 1.901, 1.160-3.115), and the nutritional intervention requirement (NRS-2002 ≥ 3) (HR, 2.802, 1.211-6.483) was significantly correlated with poor OS in NPC patients with middled age adults. Distant metastasis (HR, 2.546, 1.497-4.330), low albumin (HR, 1.824, 0.949-3.507), low hemoglobin (HR, 1.757, 1.015-3.044), low hand grip strength (HR, 1.771, 1.112-2.818), and low calf circumference (HR, 1.951, 1.074-3.545) were associated with increased risk of death in the elderly. KM analysis indicated that over 60 years, distant metastasis, low albumin, low hand grip strength, low calf circumference, and malnutritional risk (NRS-2002 ≥ 3) were correlated to prognosis of NPC patients. Low calf circumference could be a prognosis not only in elderly but also in young adults of NPC patients, whereas low albumin and distant metastasis were the prognostic factors in middle-aged and elderly patients. Patients aged over 60 years exhibited poorer OS compared with young and middle-aged adults.

PMID:37847417 | DOI:10.1007/s00520-023-08104-8

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Selective ionization of oxidized lipid species using different solvent additives in flow injection mass spectrometry

Anal Bioanal Chem. 2023 Oct 17. doi: 10.1007/s00216-023-04988-x. Online ahead of print.

ABSTRACT

Lipid oxidation in food products is a crucial problem that causes undesirable changes in the food’s flavor, texture, and nutritional value. It should be carefully monitored as it can lead to the formation of potentially toxic compounds and in that way reduce the shelf life of the product. Liquid chromatography coupled to mass spectrometry is a powerful tool to monitor the formation of oxidized lipids. However, the presence of lipid species in both their non-oxidized and oxidized forms at distinctly different concentrations can hinder the detection and identification of the less abundant oxidized species, due to coelution. In this study, a flow injection mass spectrometry approach was used to selectively ionize oxidized triacylglycerols versus their non-oxidized precursors. Three mobile phase additives were investigated (ammonium formate, sodium acetate, and sodium iodide) at three different concentrations, and ion source settings (i.e., sheath gas temperature, capillary voltage, and nozzle voltage) were optimized. A fractional factorial design was conducted to examine not only the direct effect of the operating parameters on the selectivity of ionization for the oxidized lipid species, but also to assess their combined effect. Overall, selective ionization of oxidized versus non-oxidized lipid species was favored by the use of sodium-containing solvent additives. The application of specific ion source settings resulted in an increased ionization selectivity, with sheath gas temperature and capillary voltage having the most significant influence. A selectivity factor as high as 120 could be reached by combining 0.1 mg/mL sodium-containing additives, with 250 °C sheath gas temperature and 5000 V capillary voltage. These findings will contribute to future studies on fast detection and relative quantification of low abundant oxidized triacylglycerols and their possible impact on human health.

PMID:37847408 | DOI:10.1007/s00216-023-04988-x

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Superior outcomes of total hip arthroplasty without prior lumbar arthrodesis: a systematic review and meta-analysis

Eur J Orthop Surg Traumatol. 2023 Oct 17. doi: 10.1007/s00590-023-03761-1. Online ahead of print.

ABSTRACT

PURPOSE: The number of patients undergoing total hip arthroplasty (THA) surgery after previous lumbar arthrodesis (LA) is rising. Literature suggests that LA may significantly impact pelvic biomechanics and potentially compromise the success of prosthetic hip replacement. This study aims to evaluate complication rates, dislocation rates, and revision rates in patients with prior LA undergoing THA surgery compared to those undergoing THA surgery without prior LA.

METHODS: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. The search for relevant studies was performed across five databases, including Pubmed, Scopus, Embase, Medline, and Cochrane. The selected articles were evaluated based on the Levels of Evidence (LoE) criteria. The Coleman Methodology Score (mCMS) was employed to analyze the retrospective studies. This systematic review and meta-analysis were registered in the International Prospective Register of Systematic Reviews (PROSPERO). For the outcomes that allowed for a meta-analysis performed using R software, a p < 0.05 was considered statistically significant.

RESULTS: The final analysis included seventeen studies comprising a total of 3,139,164 cases of THA. Among these cases, 3,081,137 underwent THA surgery alone, while 58,027 patients underwent THA with a previous LA. The study investigated various factors, including dislocation rates, revision rates, and complication, as well as the surgical approach and type of implant used, for both the THA-only group and the group of patients who underwent THA with prior LA. The analysis revealed a statistically significant difference (p < 0.05) for all variables studied, favoring the group of patients who underwent THA alone without prior LA.

CONCLUSIONS: This systematic review and meta-analysis demonstrated a statistically significant superiority in all analyzed outcomes for patients who underwent THA-only without prior LA. Specifically, patients with isolated THA implants experienced significantly lower incidences of THA dislocation, wound complications, periprosthetic joint infection, revision, and mechanical complications.

LEVEL OF EVIDENCE: Level IV.

PMID:37847406 | DOI:10.1007/s00590-023-03761-1

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Racial and ethnic minority participants in clinical trials of acute respiratory distress syndrome

Intensive Care Med. 2023 Oct 17. doi: 10.1007/s00134-023-07238-x. Online ahead of print.

ABSTRACT

PURPOSE: There is growing interest in improving the inclusiveness of racial and ethnic minority participants in trials of acute respiratory distress syndrome (ARDS). With our study we aimed to examine temporal trends of representation and mortality of racial and ethnic minority participants in randomized controlled trials of ARDS.

METHODS: We performed a secondary analysis of eight ARDS Network and PETAL Network therapeutic clinical trials, published between 2000 and 2019. We classified race/ethnicity into “White”, “Black”, “Hispanic”, or “Other” (including Asian, American Indian or Alaskan Native, Native Hawaiian, or other Pacific Islander participants).

RESULTS: Of 5375 participants with ARDS, 1634 (30.4%) were Black, Hispanic, or Other race participants. Representation of racial and ethnic minority participants in trials did not change significantly over time (p = 0.257). However, among participants with moderate to severe ARDS (i.e., partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 150), the difference in mortality between racial and ethnic minority participants and White participants decreased over time. In the five most recent trials, including 2923 participants with ARDS, there were no statistically significant differences in mortality between racial/ethnic groups, even after adjusting for potential confounders. In these five most recent trials, mortality was 31% for White, 31.9% for Black, 30.3% for Hispanic, and 37.1% for Other race participants (p = 0.633).

CONCLUSION: Representation of racial and ethnic minority participants in ARDS trials from North America, published between 2000 and 2019, did not change over time. Black and Hispanic participants with ARDS may have similar mortality as White participants within trials.

PMID:37847403 | DOI:10.1007/s00134-023-07238-x

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Metastatic castration-resistant prostate cancer-what are rational sequential treatment options?

Urologie. 2023 Oct 17. doi: 10.1007/s00120-023-02212-3. Online ahead of print.

ABSTRACT

BACKGROUND: In advanced prostate cancer, disease progression during ongoing androgen deprivation therapy (ADT) is referred to as castration-resistant prostate cancer (CRPC). Various therapeutic modalities are available for its treatment, including endocrine therapy, chemotherapy, poly (ADP-ribose) polymerase [PARP] inhibition, radionuclide therapy, and radioligand therapy.

OBJECTIVES: This review outlines practical aspects and considerations regarding treatment sequencing in mCRPC.

MATERIALS AND METHODS: The findings are based on existing prospective phase 3 studies that have demonstrated clinically relevant and statistically significant benefits in radiographically progression-free and/or overall survival.

RESULTS: Sequential therapy, aside from numerous patient-specific factors, depends on the treatment patients received in the hormone-sensitive prostate cancer (mHSPC) setting. Following pretreatment with ADT alone or ADT plus docetaxel in the mHSPC context, additional endocrine therapy is the standard approach. In the event of progression under combined endocrine therapy initiated in the mHSPC setting, docetaxel currently serves as the standard for the majority of patients. Patients who received triplet therapy as a pretreatment in the mHSPC scenario can be treated with radioligand therapy or second-line chemotherapy.

CONCLUSION: Various active and well-tolerated treatment options are available for patients with metastatic castration-resistant prostate cancer (mCRPC). The choice of therapy is primarily determined by previous treatments, but many other individual factors are also taken into consideration.

PMID:37847397 | DOI:10.1007/s00120-023-02212-3

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Phylogenetic and network analysis of Pediculus humanus in Nigeria reveal the presences of clade E body lice and novel haplotypes

Parasitol Res. 2023 Oct 17. doi: 10.1007/s00436-023-07999-w. Online ahead of print.

ABSTRACT

An investigation was conducted for the first time to determine the prevalence and genetic diversity of human lice, for the first time in Nigeria, using conventional PCR and sequencing methods. Three mitochondrial genes, cytochrome oxidase subunit 1 (cox1), cytochrome b (cytb), and 12S rRNA of Nigerian human lice, were amplified, sequenced, and analyzed. Overall, high prevalence (72.5%; 103/142) of lice infestation was recorded among the examined volunteers. Head lice infestation was more common 63 (61.2%) than body lice infestation 34 (33.0%). Co-infestation with both head and body lice was recorded in six humans (5.8%). The Nigerian human lice specimens were placed mostly into clade A with few in clade E, including body lice for the first time. Six, three, and eight haplotypes of Nigerian human lice were obtained for the cytb, cox1, and 12S rRNA genes, respectively. Additionally, one (E51), three (A31, A32, and E5), and six (A20, A21, A23, A24, A30, and E1) novel haplotypes were recorded for cox1, cytb, and 12S rRNA, respectively, from the Nigerian specimens which were corroborated by the ML phylogenetic trees and MJ network analyses. Genetic diversity indices indicate minimal variation in the parameters analyzed among the clades of the three genes. However, a statistically significant Snn test, negative Tajima’s D test for clade A (cox1 and 12S rRNA genes), and negative Fu and Li’s D test in clade A for cox1 gene indicate a geographical structure and the signature of population expansion of the Nigerian human lice. The findings from this study provide additional data on the human lice structure in Africa.

PMID:37847393 | DOI:10.1007/s00436-023-07999-w