Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Neuroimaging and natural language processing-based classification of suicidal thoughts in major depressive disorder.

Suicide is a growing public health problem around the world. The most important risk factor for suicide is underlying psychiatric illness, especially depression. Detailed classification of suicide in patients with depression can greatly enhance personalized suicide control efforts. This study used unstructured psychiatric charts and brain magnetic resonance imaging (MRI) records from a psychiatric outpatient clinic to develop a machine learning-based suicidal thought classification model. The study included 152 patients with new depressive episodes for development and 58 patients from a geographically different hospital for validation. We developed an eXtreme Gradient Boosting (XGBoost)-based classification models according to the combined types of data: independent components-map weightings from brain T1-weighted MRI and topic probabilities from clinical notes. Specifically, we used 5 psychiatric symptom topics and 5 brain networks for models. Anxiety and somatic symptoms topics were significantly more common in the suicidal group, and there were group differences in the default mode and cortical midline networks. The clinical symptoms plus structural brain patterns model had the highest area under the receiver operating characteristic curve (0.794) versus the clinical notes only and brain MRI only models (0.748 and 0.738, respectively). The results were consistent across performance metrics and external validation. Our findings suggest that focusing on personalized neuroimaging and natural language processing variables improves evaluation of suicidal thoughts.

Coping with Non-COVID-19 Health Problems Through Communicative Action in Cyberspace.

This study investigated how the online health information behaviors of U.S. adults with illnesses unrelated to COVID-19 virus infection affected their coping with health problems and concerns during the COVID-19 pandemic. Guided by the cybercoping model (Kim & Lee, 2014), the study examined associations between these patients' online information behaviors (information seeking and information forwarding) and coping outcomes (health problems and affective states). The study further explored the mediating roles of health coping processes (problem-and emotion-focused) in the associations between these information behaviors and coping outcomes. Survey data from 687 participants were analyzed using structural equation modeling. The results highlighted the significance of information forwarding in enhancing both coping processes and outcomes, while information seeking enhanced problem-focused coping and health-problem coping outcomes alone. These associations were more pronounced among U.S. adults without chronic conditions than among those with chronic illnesses. These findings' implications, the study's limitations, and suggestions for future research were also addressed.

Revision for unsatisfactory outcomes of scalp micropigmentation.

BACKGROUND: Scalp micropigmentation (SMP) is becoming increasingly popular. Accordingly, complications of the procedure are on the rise. However, the results of improperly performed SMP are exceedingly challenging to rectify and ultimately lead to severe mental stress and feelings of inferiority in patients. AIMS: This retrospective study aimed to explore various aspects of unsatisfactory SMP outcomes and examine corrective measures available after the procedure. MATERIALS AND METHODS: A total of 120 patients who underwent corrective surgery or procedures due to unsatisfactory outcomes after SMP were enrolled in the study. Their photographs and medical charts were reviewed retrospectively. RESULTS: Out of 120 participants, 76 were women and 43 men. In total, 107 patients (89.2%) had been treated at a tattooing or cosmetic facility at a beauty salon performing permanent makeup, 12 (10.0%) at another clinic, and one (0.8%) at an oriental medicine clinic. Of 120 patients, hair transplant surgery was performed on 74 patients (61.7%). Twenty-five (20.8%) underwent both hair transplant surgery and complementary SMP. Sixteen (13.3%) patients received laser tattoo removal and underwent SMP anew. Five patients (4.2%) had a previous tattoo removed without additional treatment. Patients' subjective satisfaction scores averaged 4.5/5. The physician's objective satisfaction score was 4.6/5. CONCLUSION: In cases where SMP is inadequately performed, satisfactory results can be achieved through appropriate revisions, such as tattoo removal, repeated SMP, or hair transplant surgery to conceal the tattoo by highly experienced medical professionals. LEVEL OF EVIDENCE: IV.

Hair transplantation versus scalp micropigmentation: A retrospective study of treatment selection in persons with female pattern hair loss.

BACKGROUND: Hair transplant (HT) is the standard treatment for female pattern hair loss (FPHL), but scalp micropigmentation (SMP) is an alternative. Currently, there are no criteria to help choose between HT and SMP. METHODS: Forty female patients with FPHL who had successfully undergone HT and SMP, were reviewed to identify factors that might help decide between treatments. Hair density (HD) and hair caliber were measured at the part line and mid-occipital region by a Folliscope. The sensitivity and specificity of HT and SMP were determined by area under the curve (AUC) and receiver operating characteristic curve. RESULTS: Patients were divided into HT (n = 23) and SMP (n = 17) groups. The follicular unit density (FUD) (HT: 62.06 ± 4.8551/cm2; SMP: 66.59 ± 3.4971/cm2) and HD (HT: 96.16 ± 16.6954/cm2; SMP: 116.08 ± 17.0520/cm2) were significantly different (p < 0.01) between groups. The AUC for FUD was 77.6% with a cutoff value of 66.83 and 87.0% (1-0.412) sensitivity. The AUC for HD was 82.4% with a cutoff value of 96.17 and 69.6% (1-0.118) sensitivity. CONCLUSIONS: HD was the most important factor when deciding between HT surgery and SMP. SMP is recommended when the HD is ≥104.6 hairs/cm2 and HT surgery is strongly recommended when the HD is ≤96.17 hairs/cm2.

Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study.

Background and Objectives: GGC repeat expansions in the NOTCH2NLC gene are associated with a broad spectrum of progressive neurologic disorders, notably, neuronal intranuclear inclusion disease (NIID). We aimed to investigate the population-wide prevalence and clinical manifestations of NOTCH2NLC-related disorders in Koreans. Methods: We conducted a study using 2 different cohorts from the Korean population. Patients with available brain MRI scans from Seoul National University Hospital (SNUH) were thoroughly reviewed, and NIID-suspected patients presenting the zigzag edging signs underwent genetic evaluation for NOTCH2NLC repeats by Cas9-mediated nanopore sequencing. In addition, we analyzed whole-genome sequencing data from 3,887 individuals in the Korea Biobank cohort to estimate the distribution of the repeat counts in Koreans and to identify putative patients with expanded alleles and neurologic phenotypes. Results: In the SNUH cohort, among 90 adult-onset leukoencephalopathy patients with unknown etiologies, we found 20 patients with zigzag edging signs. Except for 2 diagnosed with fragile X-associated tremor/ataxia syndrome and 2 with unavailable samples, all 16 patients (17.8%) were diagnosed with NIID (repeat range: 87-217). By analyzing the Korea Biobank cohort, we estimated the distribution of repeat counts and threshold (>64) for Koreans, identifying 6 potential patients with NIID. Furthermore, long-read sequencing enabled the elucidation of transmission and epigenetic patterns of NOTCH2NLC repeats within a family affected by pediatric-onset NIID. Discussion: This study presents the population-wide distribution of NOTCH2NLC repeats and the estimated prevalence of NIID in Koreans, providing valuable insights into the association between repeat counts and disease manifestations in diverse neurologic disorders.

Recurrent Acute Coronary Syndrome in Young Man with Familial Hypercholesterolemia: Efficacy of Evolocumab Add-On Treatment Demonstrated via Serial Coronary Angiography.

In patients with acute coronary syndrome (ACS), lipid-lowering therapy plays an important role in the prevention of the recurrence of cardiovascular disease. Recent guidelines recommend the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with ACS if their low-density lipoprotein cholesterol (LDL-C) levels are not adequately controlled with statins and ezetimibe. Based on this, we report a case in which administering a PCSK9 inhibitor successfully lowered the patient's LDL-C level to the target level and managed the coronary artery disease (CAD) recurrence. A 39-year-old man who was taking statins presented to the hospital with chest pain and was diagnosed with unstable angina. He started taking maximum doses of statins and ezetimibe to lower his LDL-C. However, the patient's unstable angina recurred 1 year later, and a de novo lesion with plaque rupture was demonstrated via coronary angiography. The LDL-C failed to reach the target level despite maintaining the maximum dose of statin and ezetimibe. Accordingly, evolocumab was initiated in addition to rosuvastatin/ezetimibe 20/10 mg daily. Subsequently, coronary angiography was performed twice, and on follow-up, the patient remained free of CAD recurrence. This case highlights the efficacy of lipid-lowering therapy with evolocumab in high-risk patients with repeated ACS.

Explainable multimodal prediction of treatment-resistance in patients with depression leveraging brain morphometry and natural language processing.

Although 20 % of patients with depression receiving treatment do not achieve remission, predicting treatment-resistant depression (TRD) remains challenging. In this study, we aimed to develop an explainable multimodal prediction model for TRD using structured electronic medical record data, brain morphometry, and natural language processing. In total, 247 patients with a new depressive episode were included. TRD-predictive models were developed based on the combination of following parameters: selected tabular dataset features, independent components-map weightings from brain T1-weighted magnetic resonance imaging (MRI), and topic probabilities from clinical notes. All models applied the extreme gradient boosting (XGBoost) algorithm via five-fold cross-validation. The model using all data sources showed the highest area under the receiver operating characteristic of 0.794, followed by models that used combined brain MRI and structured data, brain MRI and clinical notes, clinical notes and structured data, brain MRI only, structured data only, and clinical notes only (0.770, 0.762, 0.728, 0.703, 0.684, and 0.569, respectively). Classifications of TRD were driven by several predictors, such as previous exposure to antidepressants and antihypertensive medications, sensorimotor network, default mode network, and somatic symptoms. Our findings suggest that a combination of clinical data with neuroimaging and natural language processing variables improves the prediction of TRD.

Diagnostic uplift through the implementation of short tandem repeat analysis using exome sequencing.

To date, approximately 50 short tandem repeat (STR) disorders have been identified; yet, clinical laboratories rarely conduct STR analysis on exomes. To assess its diagnostic value, we analyzed STRs in 6099 exomes from 2510 families with mostly suspected neurogenetic disorders. We employed ExpansionHunter and REViewer to detect pathogenic repeat expansions, confirming them using orthogonal methods. Genotype-phenotype correlations led to the diagnosis of thirteen individuals in seven previously undiagnosed families, identifying three autosomal dominant disorders: dentatorubral-pallidoluysian atrophy (n = 3), spinocerebellar ataxia type 7 (n = 2), and myotonic dystrophy type 1 (n = 2), resulting in a diagnostic gain of 0.28% (7/2510). Additionally, we found expanded ATXN1 alleles (≥39 repeats) with varying patterns of CAT interruptions in twelve individuals, accounting for approximately 0.19% in the Korean population. Our study underscores the importance of integrating STR analysis into exome sequencing pipeline, broadening the application of exome sequencing for STR assessments.

Double-chambered left ventricle with a thrombus in an asymptomatic patient: A case report.

BACKGROUND: Double-chambered left ventricle (DCLV) is an extremely rare congenital disease in which the left ventricle (LV) is divided by abnormal muscle tissue. Due to its rarity, there is a lack of data on the disease, including its diagnosis, treatment, and prognosis. Accordingly, we report a case in which DCLV was diagnosed and followed up. CASE SUMMARY: A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health check. He had no specific cardiac symptoms, comorbidities or relevant past medical history. Echocardiography revealed that the LV was divided into two by muscle fibers. There were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential diagnoses. After comprehensive analysis of the images, DCLV was diagnosed. As it seemed to be asymptomatic DCLV, we decided the patient was to be observed without administering any medication. However, follow-up echocardiography revealed a thrombus in the accessory chamber (AC). Anticoagulant medication was initiated, the thrombus resolved, and the patient is currently undergoing follow-up without any specific symptoms. CONCLUSION: Asymptomatic, uncomplicated DCLV was diagnosed through multimodal imaging; however, a thrombus in the AC occurred during the follow-up. The findings highlight that multimodal imaging is essential in diagnosing DCLV, and that anticoagulation is important in its management.

Post-Hair Transplantation Complication: Kinky or Severely Curly Hair.

OBJECTIVE: To investigate the etiology and preventive measures of posttransplant kinky or curly hair growth after female hairline correction surgery. BACKGROUND: Hair transplant surgery can be accompanied by various adverse effects, one of which is severely kinky or curly hair after surgery. Posttransplant kinky or curly hair is not well-understood for its cause or prevention. METHODS: The study was targeted at a total of 980 patients who were confirmed whether they developed kinky or curly hair after female hairline correction surgery. Incidence, surgical method, degree of curliness, predisposed location, characteristics, hair caliber (thin, medium, and thick), and left-right differences were examined. RESULTS: Among the total 980 patients, posttransplant curly hair (PTCH) was manifested in 38(3.9%) patients. None of the patients who underwent surgery at the present clinic developed posttransplant kinky hair; all 38 patients showed PTCH growth. In 36 cases, transplanted hair started to grow in curly patterns around 4 months after surgery. However, the remaining 2 cases showed no curly growth pattern when the transplanted hair was short at postoperative 4 months, but started to grow curly starting at 6 to 8 months after surgery as the hair growth direction was obstructed or compressed by the existing hair. CONCLUSION: Familiarity with the cause, prevention, and management of posttransplant kinky hair and PTCH will be of great help to hair surgeons.

Higher HbA1c Is Associated With Greater 2-Year Progression of White Matter Hyperintensities.

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (ß = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (ß = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (ß = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (ß = 5.00 × 10-4; P < 0.001) and parietal (ß = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.

Precise base editing without unintended indels in human cells and mouse primary myoblasts.

Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.

Identification of bacterial pathogens in brain abscesses by metagenomic approach using nanopore 16S amplicon sequencing.

Brain abscess is medically challenging. In this study, we applied nanopore sequencing for 16S rRNA analysis and investigated its efficacy and diagnostic value for patients with brain abscesses. Genomic DNA was extracted from the pus samples (n = 27) of brain abscess, and 16S rRNA genes were amplified by PCR. Sequencing libraries were generated using a rapid barcoding kit, and the generated reads were analyzed using the EPI2ME16S workflow. A conventional culture study was performed. More sensitive identification of pathogens was made by 16S sequencing, faster than the culture study. The proportion of anaerobic bacteria identified by 16S sequencing was higher (75%) than that obtained by culturing (32%). Polymicrobial infections were identified in 10 cases (40%) by 16S sequencing, while the culture study identified multiple bacteria in only 2 cases (8%). 16S sequencing was useful for identifying the composition of polymicrobial infections, including rare pathogens, and for the initial diagnosis of space-occupying lesions.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

INTRODUCTION: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes. It is unclear whether a combination of multimedia modalities can improve bowel preparation quality, adenoma detection rates and patient-reported measures in those undergoing colonoscopy assessment. METHODS: The DIGICLEAN trial is a prospective, parallel, multicentre, colonoscopist-blinded, randomised controlled trial. The trial will enrol 1294 participants aged 45 years and older who are indicated for a colonoscopy as an outpatient with a positive faecal occult blood test, iron deficiency anaemia or rectal bleeding. Participants will be randomised into the interventional arm, where bowel preparation instructions are delivered via a web-based application which uses scheduled short messaging service, regular patient survey assessment, email and videos; or the control arm, where routine standard written, verbal or emailed instructions are administered. The web-based application will assess patient-reported bloating, constipation and dietary adherence leading up to the colonoscopy. Depending on patient responses, additional aperients may be encouraged digitally in the interventional arm with same instructions made available in written format for the control arm. Patient-reported measures will be collected in both arms the day after the procedure using the validated Newcastle ENDOPREM questionnaire. In some sites, participants will undergo digital pre-anaesthetic screening as well. The co-primary endpoints are the adenoma detection rates and patient-reported measures taken after the colonoscopy. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Western Sydney Local Health District Human Research Ethics Committee (2022/ETH00059). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000747729.

Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway.

Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Talaromyces rugulosus ventriculitis diagnosed by nanopore amplicon sequencing, 2022.

Ventriculitis has serious complications and a high mortality rate, so it is important to early identification of the pathogen for appropriate treatment. We report case of ventriculitis caused by Talaromyces rugulosus, a rare pathogen, in South Korea. Affected patient was immunocompromised. Repeated cerebrospinal fluid culture tests were negative, but the pathogen was identified by fungal internal transcribed spacer amplicon nanopore sequencing. The pathogen was detected outside the endemic area of talaromycosis.

Do age-based discontinuation recommendations influence cervical cancer screening rates? Evidence from the United States' Behavioral Risk Factor Surveillance System, 2016 and 2018.

The United States Preventive Services Task Force (USPSTF) recommends that women with adequate prior screening and average cervical cancer risk discontinue routine cervical cancer screening after age 65. This study's objective was to estimate how the USPSTF recommendation affects Papanicolaou (Pap) test rates among women at age 66 in the United States. We used nationally representative 2016 and 2018 Behavioral Risk Factor Surveillance System data for women ages 56-76 (n = 226,031) and a regression discontinuity design to estimate changes in annual Pap test rates at age 66. Among women age 66-76, 22.5% reported receiving a Pap test within the past one year. At age 66, annual Pap rates declined by 5.9 percentage points (p.p.) (95% Confidence Interval [CI]: -7.7, -4.1) off a pre-66 rate of 39%. The change varied by race/ethnicity, education, and marital status. Pap rates did not change discretely for non-Hispanic Black women (0.8 p.p.; 95% CI: -5.4, 7.1) but did for women from other racial/ethnic groups. The decline was larger for women who graduated college (-9.0 p.p.; 95% CI: -12.0, -5.9) than for women without a college degree and for women who were never married (-9.4 p.p., 95% CI: -17.3, -1.5) than for women who were married/partnered or divorced/separated. The USPSTF recommendation to discontinue cervical cancer screening after age 65 leads to a sharp decline in Pap test rates at age 66 but disparately affects women based on race, education and marital status. Further study is needed to assess the consequences of these changes.

Gastric mucosal swab as an alternative to biopsy for Helicobacter pylori detection.

BACKGROUND AND AIMS: Gastric mucosal swab may be a more sensitive sampling method than a biopsy since Helicobacter pylori (H. pylori) resides within the mucus layer. We compared the diagnostic performance of the rapid urease test (RUT) and bacterial load of H. pylori between swabs and tissue biopsy. METHODS: Overall, 276 RUTs (138 swab-RUTs (S-RUT) and 138 tissue-RUTs (T-RUT)) were performed. To diagnose H. pylori infection, RUT, H. pylori PCR, and 16S ribosomal RNA gene sequencing of tissue and swab were used, and its infection was defined as at least two positives of the six test results. The diagnostic performances of RUTs and the H. pylori bacterial load using qPCR were compared between swab and biopsy. RESULTS: The positivity rates of S-RUT and T-RUT were 35.5% (49/138) and 25.4% (35/138), respectively. The sensitivity, specificity, and accuracy of S-RUT were 98.0%, 100.0%, and 99.2%, while those of T-RUT were 70.0%, 100%, and 89.1%, respectively. The sensitivity and accuracy were significantly higher for S-RUT than for T-RUT (p < 0.05). In the patients with atrophic gastritis and intestinal metaplasia, S-RUT showed significantly higher sensitivity than T-RUT. qPCR showed that the swab contained a significantly higher H. pylori bacterial load than tissue biopsy (22.92-fold and 31.61-fold in the antrum and body (p < 0.05), respectively). CONCLUSIONS: Gastric mucosal swabs showed higher RUT accuracy and H. pylori bacterial load than a tissue biopsy. This may be an alternative to a biopsy when diagnosing H. pylori infection during endoscopy is necessary. (ClinicalTrials.gov, NCT05349578).

Effectiveness and cost-effectiveness of palliative care in natural experiments: a systematic review.

CONTEXT: Investigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. 'Natural experiments' offer opportunities to generate credible causal treatment effect estimates from observational data. OBJECTIVES: We aimed first to review studies that employed 'natural experiments' to evaluate palliative care, and second to consider implications for expanding use of these methods. METHODS: We searched systematically seven databases to identify studies using 'natural experiments' to evaluate palliative care's effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis. RESULTS: We included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect. CONCLUSION: Among the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of 'natural experiments'. Such studies would improve the quality of the evidence base.