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Results for “Observational Study”

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PubMed1991

Hypoxaemia during anaesthesia--an observer study.

We have investigated 296 inpatients in a single-blind observer study to determine the incidence, degree and duration of hypoxaemia during anaesthesia. The clinical recognition of hypoxaemia, period of time until recognition and risk factors were studied. Oxygen saturation (Spo2) was monitored continuously with a pulse oximeter (Ohmeda, model 3700). One or more episodes of mild hypoxaemia (Spo2 86-90%) were recorded in 53% of patients. Severe hypoxaemia with Spo2 values less than 81% were recorded in 20% of patients. The mild hypoxaemic episodes lasted up to 34.6 min (mean 2.3 min) and 70% were not detected by the anaesthetist. In the remaining 30% of episodes, the anaesthetist diagnosed the complication with a mean time delay of 70 s. After intervention a mean time delay of 57 s was recorded until Spo2 exceeded 90%. Utilizing a stepwise multiple logistic regression analysis, we found that risk factors associated with a greater incidence of hypoxaemia were patient age (P less than 0.005) and anaesthetic technique (P less than 0.00001). We conclude that hypoxaemic episodes in our operating rooms are common during anaesthesia and suggest preoxygenation in all patients in addition to administration of supplementary oxygen during arousal from anaesthesia and during transfer to the recovery room.

Adolescent↗

PubMedDate not supplied

Supplemental immunoglobulin (ivIgG) treatment in 163 patients with sepsis and septic shock--an observational study as a prerequisite for placebo-controlled clinical trials.

In a multicenter observational study of 163 medical and surgical patients with a total of 173 episodes of sepsis or septic shock (Elebute sepsis score: 19.0 +/- 0.5), the effects of supplemental i.v. immunoglobulin (i.v. IG) treatment (unmodified polyvalent IgG pH 4.25, n = 123; for Pseudomonas sepsis, n = 50, Pseudomonas IgG) on multiple organ failure (MOF) were investigated by means of APACHE II score changes (pretreatment: 23.7 +/- 0.6). In 44% of the cases ("responders"), a prompt improvement in APACHE II score (defined as decrease greater than or equal to 4) was evident from day 0 to day 4 after onset of therapy, thus being in close time relationship to the i.v. IG administration. This improvement, associated with a better prognosis (mortality 24% vs. 55%), was found in all subgroups, most importantly the following: polyvalent IgG vs. Pseudomonas IgG treatment; medical vs. surgical patients; moderate vs. severe MOF; and gram-positive vs. gram-negative septicemia. In a small-sized second comparative nonrandomized control group (n = 27, antibiotic treatment alone) of septic patients (Elebute: 14.7 +/- 1.0) with similar MOF severity (APACHE II: 23.6 +/- 1.4), the response rate (30%) was, though not statistically significant, lower by one-third. The optimal baseline score ranges for patient inclusion into future placebo-controlled randomized i.v. IG trials were found to be 20-35 for the APACHE II score and 12-27 for the Elebute score.

Adult↗

PubMedDate not supplied

Observational studies of children from diary to ethnogram. A century of progress.

A survey of methodology within observational study is attempted. Personalized baby biographies are seen to provide a foundation for more rigorous study including time and event sampling utilizing technological aids. The essence of ecology is included within an increasingly objective approach leading up to the possibility of utilization of the principles and practice of ethology. Naturalistic observation can be seen to be a necessary element within modern behavioral study.

Child↗

PubMed2026

Real-world emergence of nirsevimab resistance in breakthrough infections with respiratory syncytial virus-B: a multicentre observational study in France.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants. Nirsevimab, a long-acting monoclonal antibody targeting a conserved epitope on the prefusion F protein (site Φ), has shown high efficacy in clinical trials and early real-world studies. Although widespread resistance has not been reported, concerns remain about the emergence of escape variants, particularly among RSV-B viruses. During the 2024-25 RSV season in France, RSV-B predominated, providing a unique opportunity to examine breakthrough infections with RSV-B and resistance at a large scale. The study aimed to characterise RSV escape from nirsevimab using genotypic and phenotypic methods. METHODS: This POLYRES-2 project was a multicentre, national, observational study conducted in hospital settings (inpatients and outpatients) across France during the 2024-25 RSV season. We included infants aged 1 year or under with a RT-PCR-confirmed RSV infection in routine care, regardless of whether they had received nirsevimab. Infants were identified through hospital virology laboratory databases. Each participating centre was requested to include a balanced number of nirsevimab-exposed and non-exposed infected infants throughout the study period. Clinical data were retrieved from electronic medical records. We compared RSV susceptibility to nirsevimab in infants who received nirsevimab with that in nirsevimab-naive infants. Respiratory samples were sequenced for full-length RSV genomes. To ensure reliability, phylogenetic and mutational analyses were restricted to high-quality sequences with greater than or equal to 90% genome coverage and complete reads across the nirsevimab-binding site. Clinical RSV isolates were tested for neutralisation by nirsevimab. We analysed F candidate substitutions using a fusion inhibition assay. The primary outcomes were presence of resistance-associated substitutions (RASs) in the RSV F protein (site Φ) and phenotypic resistance to nirsevimab. FINDINGS: Among 1023 RSV-infected infants, 858 (83·9%) had full-length RSV genome sequences: 419 (48·8%) from nirsevimab-treated breakthrough infections (212 [50·6%] RSV-A, 207 [49·4%] RSV-B) and 439 (51·2%) from nirsevimab-naive infants (192 [43·7%] RSV-A, 247 [56·3%] RSV-B). RASs were identified in two of 195 RSV-A breakthrough infections (1·0%) and in 23 of 184 RSV-B breakthrough infections (12·5%). In RSV-A, the only RAS was F:K209E, conferring intermediate resistance. In RSV-B, resistance was more frequent and diverse than in RSV-A: 12 of 23 (52.2%) resistant viruses carried a substitution at residue 208 (F:N208D, F:N208I, F:N208K, F:N208S, or F:N208Y). Additional novel substitutions, including F:I64V/F:K65E, F:K68I, F:L204S, and F:P205S, also mediated resistance. Notably, a resistant RSV-B variant (F:N208S) was detected almost 1 year after prophylaxis. No resistant RSV was detected in nirsevimab-naive infants. INTERPRETATION: Resistance to nirsevimab in RSV-B can emerge in real-world settings, affecting around 12% of breakthrough infections and showing greater diversity than previously recognised, although the clinical impact remains constrained by available evidence. Detection of resistant variants long after prophylaxis highlights the need for extended genomic surveillance. Integration of clinical and virological data will be essential to sustain the long-term effectiveness of RSV monoclonal antibody programmes. FUNDING: This study was supported by a grant from the Agence Nationale de Recherche sur le Sida et les hépatites virales - Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Humans↗

PubMed1990

[High-dosage oral magnesium therapy in arrhythmias. Results of an observational study in 1.160 patients with arrhythmia].

In the treatment of cardiac arrhythmias of varying genesis, an "observational study" in 1,160 patients showed that a high-dose oral magnesium preparation (Magnesium-Diasporal N 300 Granulat) was effective. In 82% of the patients observed, a dose of at least 300 mg magnesium/day produced good to very good results. Adverse effects of the drug were observed in only 1.6% of the patients. For all groups, the "success parameters" improved significantly. High-rate arrhythmias showed a better response to magnesium treatment than did low-rate arrhythmias, with a close correlation being found with the heart rate at the start of treatment. High-dose oral magnesium had a positive effect on concomitant hypertension. At a dosage of 300 mg treatment should be continued for at least 6 weeks.

Adult↗

PubMed2026

Strengthening the Reporting of Observational Studies in Epidemiology Enhanced Prevalence and Incidence Criteria (STROBE EPIC): An Extension of the STROBE Statement.

Prevalence and incidence are fundamental metrics with numerous applications in epidemiology. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline lacks specific items for reporting studies of disease prevalence or incidence. To address this gap, the STROBE Enhanced Prevalence and Incidence Criteria (STROBE EPIC) extension was developed in accordance with established methods for reporting guideline development. The authors generated an initial list of reporting items, conducted a modified Delphi process, and convened a face-to-face consensus meeting to confirm the need for a STROBE extension and to generate an early version of the checklist. They conducted 2 further Delphi surveys, first extending from typhoid and other invasive salmonelloses to all infectious diseases, and then to noncommunicable diseases and injuries. Finally, experts piloted the checklist on relevant manuscripts to critically assess if it was clear, concise, complete, and free of errors. An executive group curated the checklist after every survey round. The STROBE EPIC checklist comprises 47 items in the domains of title (1 item), abstract (2 items), introduction (1 item), methods (25 items), results (6 items), discussion (7 items), and other information (5 items). STROBE EPIC items address reporting of study design, adjustment factors for underreporting and underdiagnosis, denominator population estimation, case ascertainment methods, factors producing artefactual changes to observed disease prevalence or incidence, limitations of incomplete surveillance coverage, generalizability of short-duration studies, and data availability. The authors anticipate that the STROBE EPIC extension will be used by researchers, authors, modelers, burden-of-disease researchers, peer reviewers, and journal editors to optimize the presentation of epidemiologic evidence to support diverse health policy decisions.

Humans↗

PubMed2026

TCGA-based identification of prognostic biomarkers and candidate traditional Chinese medicine compounds in papillary thyroid carcinoma: An observational study.

This study aimed to identify prognostic genes associated with papillary thyroid carcinoma (PTC) and explore candidate traditional Chinese medicine (TCM) compounds using integrated bioinformatics and molecular docking. In this observational study, PTC gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. Differentially expressed genes were screened using differential-expression sequencing (DESeq2), followed by protein-protein interaction network analysis to identify hub genes. Their expression, diagnostic value, immune relevance, prognostic significance, protein-level validation, and single-cell distribution were assessed using gene expression profiling interactive analysis, receiver operating characteristic analysis, immune infiltration analysis, Kaplan-Meier survival analysis, the human protein atlas, and single-cell RNA-sequencing data. Candidate TCM compounds were predicted using symptom mapping (SymMap) and the TCM Systems Pharmacology Database and Analysis Platform, and molecular docking was performed to evaluate potential ligand-target interactions. Five hub genes, colony-stimulating factor 2, apolipoprotein E, fibronectin 1 (FN1), collagen type I alpha 1 chain (COL1A1), and intercellular adhesion molecule 1, were identified and found to be significantly upregulated in PTC tissues, with diagnostic value in receiver operating characteristic analysis. Immune infiltration analysis showed associations with macrophages, dendritic cells, and T helper 1 cells, whereas single-cell analysis demonstrated heterogeneous expression across immune and stromal cell populations, including fibroblasts. Higher FN1 and COL1A1 expression was associated with poorer outcomes. Immunohistochemistry supported the expression patterns, while single-cell analysis provided exploratory cell-type-level context for the cellular distribution of selected genes. Ginseng and Smilax glabra were predicted as common candidate TCMs, and docking suggested favorable binding between their active compounds and selected hub targets. Colony-stimulating factor 2, apolipoprotein E, FN1, COL1A1, and intercellular adhesion molecule 1 may be biologically relevant hub genes in PTC, while FN1 and COL1A1 may have prognostic value. Predicted TCM compounds provide preliminary computational evidence for possible compound-target interactions, requiring experimental and clinical validation.

Female↗

PubMed2025

Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study.

BACKGROUND: Rising antimicrobial resistance of Helicobacter pylori is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in H pylori and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin. METHODS: In this retrospective phenotypic and genotypic observational study, we included 1011 H pylori whole-genome sequences and strains of known geographical origin from the H pylori Genome Project (HpGP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 HpGP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify 23S rRNA and gyrA variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, 23S rRNA 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, gyrA A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype-phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete HpGP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the HpGP genomes and 768 whole-genome sequences retrieved from the US National Center for Biotechnology Information Sequence Read Archive repository. Associations between resistance genotypes, H pylori subpopulations, and minimum inhibitory concentrations (MICs) were tested. FINDINGS: Clarithromycin-resistant and levofloxacin-resistant HpGP strains were estimated with a sensitivity and specificity of 100%, with all confidence intervals ranging from 96% to 100%. The combined analysis (n=1779) found the highest prevalence of clarithromycin resistance in the western Pacific region (173 [51·2%] of 338 in southeast Asia and 75 [29·8%] of 252 in eastern Asia), north African region (seven [38·9%] of 18), and western Asian region (12 [31·6%] of 38), whereas the highest prevalence of levofloxacin resistance was found in south Asia (14 [51·85%] of 27), Central America (48 [38·7%] of 124), eastern Europe (four [36·4%] of 11), and southern Africa (three [33·3%] of nine). Similarly, 23S rRNA and gyrA genotypes are variable across H pylori subpopulations. MIC values changed depending on the specific mutation in 23S rRNA (mean clarithromycin MIC 24·61 mg/L [95% CI 12·27-36·96] for 2143A→G and 142·25 mg/L [95% CI 77·88-206·61] for 2142A→G) and gyrA (mean levofloxacin MIC 9·66 mg/L [95% CI 6·75-12·56] for mutations on codon 91, and 27·97 mg/L [95% CI 25·82-30·11] for mutations on codon 87). INTERPRETATION: Mutations in specific genes are reliable indicators to clarithromycin and levofloxacin resistance in H pylori, making them useful markers for the development of diagnostic assays and molecular monitoring. Our results suggest that using clarithromycin and levofloxacin empirically, without previous susceptibility testing, is unsuitable in all geographical regions covered by this study. FUNDING: Intramural Research Program of the US National Cancer Institute, the European Research Council, and the Spanish Ministry of Science and Innovation.

Helicobacter pylori↗

PubMed2025

WHO global gonococcal antimicrobial surveillance programmes, 2019-22: a retrospective observational study.

BACKGROUND: Gonorrhoea and gonococcal antimicrobial resistance (AMR) remain global public health concerns, and enhanced quality-assured global surveillance of gonococcal AMR is imperative to inform management guidelines and public health policies. We aimed to describe the results of surveillance of gonococcal AMR conducted globally by WHO and discuss the actions needed to retain our ability to treat gonorrhoea. METHODS: In this retrospective observational study, we present gonococcal AMR data reported to WHO by 77 countries between Jan 1, 2019, and Dec 31, 2022. Gonococcal isolates were tested for minimum inhibitory concentrations of one to four key antimicrobials (ceftriaxone, cefixime, azithromycin, and ciprofloxacin) in each country. We used breakpoints for resistance and decreased susceptibility to antimicrobials from the European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory and Standards Institute. FINDINGS: 29 (39%) of 75 participating countries reported at least one isolate with resistance or decreased susceptibility to ceftriaxone, 28 (50%) of 56 reported resistance or decreased susceptibility to cefixime, 58 (88%) of 66 reported resistance to azithromycin, and 74 (99%) of 75 reported resistance to ciprofloxacin. Globally, azithromycin resistance is increasing, as is resistance or decreased susceptibility to ceftriaxone and cefixime, especially in the WHO Western Pacific region. Resistance to ciprofloxacin remained very high globally. Since 2017-18, the numbers of reporting countries, examined isolates, and resistant isolates have increased. However, surveillance levels remain inadequate in central America and the Caribbean, eastern Europe, and the WHO African, Eastern Mediterranean, and South-East Asia regions. INTERPRETATION: Global AMR surveillance conducted by WHO is expanding and, in selected countries, improving through standardisation and quality assurance, as well as implementation of extragenital sampling, test of cure, and whole-genome sequencing. This approach provides evidence-based data for management guidelines and public health policies. Improvements in prevention, early diagnosis, treatment of patients and their contacts, surveillance (of infection rates, AMR, treatment failures, and antimicrobial use), and antimicrobial stewardship are essential. WHO supports this work through several global action plans on AMR, new global gonorrhoea treatment recommendations, surveillance, and research. FUNDING: None.

Neisseria gonorrhoeae↗

PubMed2025

Estimating the association of antimicrobial resistance genes with minimum inhibitory concentration in Escherichia coli: an observational study.

BACKGROUND: Surveillance and prediction of antibiotic resistance in Escherichia coli relies on curated databases of genes and mutations. We aimed to quantify the effect of acquiring specific genetic elements on minimum inhibitory concentrations (MICs) for particular antibiotic-species combinations, addressing the current scarcity of such data in existing databases. METHODS: For this observational study, we evaluated a collection of E coli isolates with linked whole-genome sequencing and MIC data, originating from human urinary or bloodstream infections obtained from the Oxford University Hospitals National Health Service Foundation Trust in Oxfordshire, UK. We used multivariable interval regression models to estimate the change in MIC (with 95% CIs) for specific antibiotics associated with the acquisition of antibiotic resistance genes and associated mutations in the National Center for Biotechnology Information AMRFinder database, with and without an adjustment for population structure. We then tested the ability of these models to predict MIC and binary resistance or susceptibility using leave-one-out cross-validation. FINDINGS: We evaluated 2875 E coli isolates obtained during 2013-2018 and 2020. Although most ARGs and resistance mutations (89 [80%] of 111) were associated with an increased MIC, a much smaller number (27 [24%] of 111) was found to be putatively independently resistance-conferring (ie, associated with an MIC above the European Committee on Antimicrobial Susceptibility Testing breakpoint) when acquired in isolation. We found evidence of differential effects of acquired ARGs and resistance mutations between different generations of cephalosporin antibiotics and showed that sub-breakpoint variation in MIC can be linked to genetic mechanisms of resistance. 20 697 (83·3%; range 52·9-97·7 across all antibiotics) of 24 858 MICs were correctly exactly predicted and 23 677 (95·2%; 87·3-97·7) of 24 858 MICs were predicted to within one doubling dilution. INTERPRETATION: Quantitative estimates of the independent effect of the acquisition of ARGs on MIC add to the interpretability and utility of existing databases. Compared with approaches using machine learning models, the use of these estimates yields similar or better performance in the prediction of antibiotic resistance phenotype with more readily interpretable results. The methods outlined here could be readily applied to other antibiotic-pathogen combinations. FUNDING: The National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC).

Escherichia coli↗

PubMed2025

Rapid pan-microbial metagenomics for pathogen detection and personalised therapy in the intensive care unit: a single-centre prospective observational study.

BACKGROUND: Most clinical metagenomic studies do not provide rapid results, detect pathogens from all microbial kingdoms, or measure clinical impacts. We aimed to evaluate the feasibility, performance, and clinical impacts of a rapid pan-microbial respiratory metagenomic service for patients admitted to intensive care units (ICUs). METHODS: This was a single-centre observational study of a rapid metagenomics service that tests respiratory samples from ICU patients at Guy's and St Thomas' hospitals, London, UK, between Dec 5, 2023, and April 12, 2024. Testing used a previously published pan-microbial metagenomics workflow, which simultaneously detects bacteria, fungi, and DNA and RNA viruses; provides same-day preliminary results after 2 h; and provides final results after 24 h. Patients were included if they were aged 18 years or older, admitted to the ICU, had confirmed respiratory failure requiring supplemental oxygen or advanced airway support, and had at least one of the following: (1) clinical suspicion of lower respiratory tract infection based on clinical, biochemical, or radiological findings, (2) sepsis of unknown origin, and (3) concern from an intensive care physician regarding inflammatory pathology. Patients with a suspected or confirmed containment level three organism were excluded. The outcome was performance characteristics of the metagenomic test compared with routine diagnostic testing, detection of additional pathogens by metagenomics, change in antimicrobial prescribing within 24 h of testing, and initiation of immunomodulation. FINDINGS: We processed 114 samples (1-5 per day) from 74 patients (39 [53%] female and 35 [47%] male). 107 (94%) of 114 samples passed quality control, of which 101 (94%) provided same-day preliminary results. Bacteria were detected in 45 (43%) of 104 tested specimens, fungal organisms in 17 (16%) of 104 tested specimens, and viruses in 28 (34%) of 83 tested specimens. Sensitivity in lower respiratory tract samples after 24 h was 97% (95% CI 87-100) for bacteria, 89% (65-99) for fungi, and 89% (71-98) for viruses, with only one false positive for bacteria. Metagenomics identified 42 pathogens not detected by other tests in 32 (30%) of 107 samples. Antimicrobial therapy was changed after metagenomic results from 30 (28%) of 107 samples: 22 (21%) were de-escalated and eight (7%) were escalated. Metagenomics contributed to the initiation of immunomodulation in 15 (20%) of 74 patients for a range of inflammatory conditions. Pathogens with clinical significance to local infection control or national public health were found in ten (14%) of 74 patients, including three invasive Group A streptococci, two parvovirus B19, and one each of HIV-1, measles virus, Mycobacterium tuberculosis, Neisseria meningitidis, and Mycoplasma pneumoniae. INTERPRETATION: Respiratory metagenomics for ICU patients showed good performance and turnaround time, and diverse clinical and public health benefits. This ability to inform both personalised patient therapy and infectious disease surveillance needs evaluation in multicentre studies. FUNDING: None.

Humans↗

PubMed2026

Widespread circulation of Alongshan virus in Austria and serological evidence for infection in humans: a nationwide molecular and serological observational study.

BACKGROUND: Alongshan virus, a segmented RNA virus in the Jingmenvirus group of flaviviruses, was first identified in 2017 in China in patients with tick-borne encephalitis-like illness. Alongshan virus has since been detected in ticks and mammals in several European countries. In this study, we aimed to characterise the temporal and geographical distribution of Alongshan virus in Austria through nationwide tick surveillance combined with serological and molecular screening in individuals with suspected tick-borne encephalitis or tick exposure. METHODS: In this nationwide molecular and serological observational study, we conducted a PCR-based screening of ticks collected across Austria in 2024, using flagging, animal hosts, and citizen submissions. We also collated genomic data from stored nucleic acid extracts from ticks collected in Austria in 2005 and 2013 in previous surveillance studies and stored extracts of paired tick-human samples collected between 2015 and 2018. Alongshan virus-positive tick samples were subjected to whole-genome sequencing and phylogenetic analysis. In addition to tick samples, blood samples from Austrian patients with reported tick bite or suspected tick-borne encephalitis, submitted to the National Reference Center for Human Arbovirus Infections, Austria, were screened for Alongshan virus infection and subjected to serological and molecular testing. FINDINGS: 2952 ticks were collected between Feb 1, 2024, and Dec 6, 2024, from 29 (83%) of 35 NUTS-3 regions in Austria; the median detection rate for Alongshan virus was 1·2% (IQR 0·4-3·5). In addition, 1816 archived tick samples were analysed, with three testing positive for Alongshan virus. For the virus-positive samples, phylogenetic analysis showed that sequences from Austria grouped within the European clade, with Austrian sequences from the same region showing high sequence similarity. 1361 human serum samples collected between March 1, 2023, and May 16, 2025, were assessed for anti-Alongshan virus IgG antibodies. Two individuals had high antibody titres against Alongshan virus proteins VP1a and VP2. INTERPRETATION: Our study shows detection of Alongshan virus in archived tick samples dating back to 2005, representing the earliest documented occurrence of the virus to date and suggesting that Alongshan virus has been circulating in Austria for at least two decades. The detection of Alongshan virus-specific antibody titres in two individuals suggests past infection and previously unrecognised exposure. These results highlight the need for continued molecular surveillance of tick populations and serological monitoring in humans to define the epidemiology and public health relevance of Alongshan virus in Europe. FUNDING: One Health surveillance and Vector monitoring for cross-border pathogens (OH SURVector) and UNITED4Surveillance.

Adolescent↗

PubMed2026

Microbiological analysis and whole-genome sequencing of Neisseria gonorrhoeae from the microbiological failures in the international, zoliflodacin, phase 3, clinical trial for treatment of uncomplicated urogenital gonorrhoea: a retrospective, genomic, observational study.

BACKGROUND: Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1). METHODS: In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019-March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L). FINDINGS: All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013-23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10-43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39-77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs. INTERPRETATION: In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests reinfections and not treatment failures. In addition, 59% of the zoliflodacin microbiological failures, all in anogenital sites, had no obvious microbiological explanation based on the low zoliflodacin MICs, previous pharmacodynamic studies, and no evidence of resistance selection after zoliflodacin therapy. A reinfection as the cause for these microbiological failures could not be excluded. We recommend that WGS is implemented in future randomised controlled trials for gonorrhoea treatment to further evaluate possible microbiological failures, exclude reinfections (to avoid underestimating the cure rates), and characterise antimicrobial resistance determinants. FUNDING: GARDP through grants from Germany BMFTR (03KA1831), UK DHSC as part of GAMRIF, Japan MHLW, the Netherlands' Ministry of Health, Welfare and Sport and Directorate-General for International Cooperation, the Federal Office of Public Health of Switzerland, the Canton of Geneva, Switzerland, and Örebro University Hospital, Sweden.

Humans↗

PubMed1992

An observational study of the affective concomitants of mastery in infants.

The hypothesis that attempts at motor mastery were accompanied by positive affective responses was tested in an observational study of 9-11-month old infants in a daycare setting. Five infants were observed as they attempted three age-appropriate motor tasks--pulling to stand, standing with support, and taking steps with support. Positive affective responses included smiling, babbling, and laughing. The five infants were observed for a total of 82 hours. The proportion of positive affective behaviors associated with practicing new motor tasks was compared to the proportion associated with well-practiced tasks. The hypothesis that more positive affective behaviors would be associated with attempts at mastering the new motor tasks was confirmed. There was no diminution in the association between the new motor tasks and positive affect as the infants continued to practice and master the three motor tasks. The results are discussed in terms of individual differences in mastery motivation and the often suggested continuity between early mastery motivation and later competencies.

Child↗

PubMedDate not supplied

[Elimination of fat emulsions of various concentrations from the blood. Observational study in the intravenous administration of Lipovenös 10% and 20% in premature infants with very low birth weight].

Within the scope of an observation study 40 premature low birth weight infants requiring parenteral nutrition received either 10% or 20% lipid emulsions (Lipovenös) for 7 days. The 10% lipid emulsion differs from the 20% lipid emulsion in the higher phospholipid/triglyceride-ratio (0.06 resp. 0.12). Lipid infusion was commenced at 0.5 g triglyceride/kg/24 hours and increased steadily to 2 g triglyceride/kg/24 hours. The aim of the study was to compare the effects of the two intravenously administered lipid emulsions on serum clearance. The serum concentrations of triglyceride and cholesterol did not change significantly during the infusion with 20% Lipovenös. Significant increases in the triglyceride and cholesterol content were observed only in the serum of the patients who were given the 10% Lipovenös. The reduced lipid serum clearance is attributable to the higher content of phospholipids in the 10% lipid emulsion. With regard to the risk of high cholesterol concentrations and an abnormal LPX serum accumulation, administration of 20% lipid emulsion is preferable to 10% lipid emulsion, also during the neonatal period.

Cholesterol↗

PubMed2025

Clinical utility of comprehensive genomic profiling test for colorectal cancer: a single institution prospective observational study.

PURPOSE: Next-generation sequencing (NGS) has revolutionized cancer treatment by enabling comprehensive cancer genomic profiling (CGP) to guide genotype-directed therapies. While several prospective trials have demonstrated varying outcomes with CGP in patients with advanced solid tumors, its clinical utility in colorectal cancer (CRC) remains to be evaluated. METHODS: We conducted a prospective observational study of CGP in our hospital between September 2019 and March 2024. Overall survival (OS) of the patients who received CGP-based therapy and those did not was compared, and genomic variables associated with OS were evaluated. RESULTS: A total of 100 patients with CRC underwent CGP using four platforms. The median patient age was 67 years, and most had a good performance status. The most frequent genomic alterations were TP53 (82%), APC (82%), and KRAS (55%). Actionable mutations such as ERBB2 amplification and BRAF V600E were identified in some patients, and 9% received CGP-based therapy, including immune checkpoint inhibitors for tumor mutational burden-high or microsatellite instability-high tumors. Patients receiving CGP-based therapy had longer OS from expert panel discussion (16.0 vs. 10.8 months) compared to those who did not. Alterations in TP53, SMAD4, and NF1 were associated with worse OS. Interestingly, PTEN mutations were linked to improved survival. TP53 alterations were more common in left-sided CRC. CONCLUSION: Although some patients with CRC received CGP-guided therapy, a statistically significant survival benefit was not observed. However, TP53 and SMAD4 mutations were identified as negative prognostic markers, indicating their potential as targets for future drug development.

Humans↗

PubMed1990

Hypoxemia in the postanesthesia care unit: an observer study.

To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes.

Adolescent↗

PubMed1990

Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.

The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.

Adult↗