Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic ...treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized.
This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics.
In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV
) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (
= 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV
were less for PEx with antibiotic changes than for those without changes (odds ratio OR, 0.89 95% confidence interval (CI), 0.80-0.98). The odds of returning to ⩾100% of baseline ppFEV
did not differ between PEx with versus without antibiotic changes (OR, 0.94 95% CI, 0.86-1.03). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 95% CI, 1.12-1.22).
In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.
To provide a detailed electroclinical description and expand the phenotype of PIGT-CDG, to perform genotype-phenotype correlation, and to investigate the onset and severity of the epilepsy associated ...with the different genetic subtypes of this rare disorder. Furthermore, to use computer-assisted facial gestalt analysis in PIGT-CDG and to the compare findings with other glycosylphosphatidylinositol (GPI) anchor deficiencies.
We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT.
All patients had hypotonia, severe developmental delay, and epilepsy. Epilepsy onset ranged from first day of life to two years of age. Severity of the seizure disorder varied from treatable seizures to severe neonatal onset epileptic encephalopathies. The facial gestalt of patients resembled that of previously published PIGT patients as they were closest to the center of the PIGT cluster in the clinical face phenotype space and were distinguishable from other gene-specific phenotypes.
We expand our knowledge of PIGT. Our cases reaffirm that the use of genetic testing is essential for diagnosis in this group of disorders. Finally, we show that computer-assisted facial gestalt analysis accurately assigned PIGT cases to the multiple congenital anomalies-hypotonia-seizures syndrome phenotypic series advocating the additional use of next-generation phenotyping technology.
Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid ...bolus to prevent cardiovascular collapse during intubation of critically ill adults.
We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure <65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777.
Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% 95% CI -7·1% to 9·7%; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure <65 mm Hg 11 7% in the bolus group vs ten 6% in the no-bolus group, new or increased vasopressor 32 19% vs 31 18%, cardiac arrest within 1 h seven 4% vs two 1%, death within 1 h of intubation two 1% vs one 1%). In-hospital mortality was not significantly different in the fluid bolus group (48 29%) compared with no fluid bolus (59 35%).
Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial.
US National Institutes of Health.
Background. We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in ...Lilongwe, Malawi. Methods. After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50:5:1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. Results. A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. Conclusions. Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect ∼90% of acute cases.
Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques ...that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals.
A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi.
Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant.
Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI.
Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.
Rivers of the Arctic will become ever more important for the global climate, since they carry a majority of continental dissolved organic carbon flux into the rapidly changing polar ocean. Aqueous ...organics comprise a wide array of functional groups, several of which are likely to impact coastal and open water biophysical properties. Light attenuation, interfacial films, aerosol formation, gas release and momentum exchange can all be cited. We performed Lagrangian kinetic modeling for the evolution of riverine organic chemistry as the molecules in question make their way from the highlands to Arctic outlets. Classes as diverse as the proteins, sugars, lipids, re-condensates, humics, bio-tracers and small volatiles are all included. Our reduced framework constitutes an idealized northward flow driving a major hydrological discharge rate and primarily representing the Russian Lena. Mountainous, high solute and tundra sources are all simulated, and they meet up at several points between soil and delta process reactors. Turnover rates are parameterized beginning with extrapolated coastal values imposed along a limited tributary network, with connections between different terrestrial sub-ecologies. Temporal variation of our total dissolved matter most closely resembles the observations when we focus on the restricted removal and low initial carbon loads, suggesting relatively slow transformation along the water course. Thus, channel combinations and mixing must play a dominant role. Nevertheless, microbial and photochemical losses help determine the final concentrations for most species. Chemical evolution is distinct for the various functionalities, with special contributions from pre- and post-reactivity in soil and delta waters. Several functions are combined linearly to represent the collective chromophoric dissolved matter, characterized here by its absorption. Tributaries carry the signature of lignin phenols to segregate tundra versus taiga sources, and special attention is paid to the early then marine behaviors of low molecular weight volatiles. Heteropolycondensates comprise the largest percentage of reactive carbon in our simulations due to recombination/accumulation, and they tend to be preeminent at the mouth. Outlet concentrations of individual structures such as amino acids and absorbers lie above threshold values for biophysical influence, on the monolayer and light attenuation. The extent of coastal spreading is examined through targeted regional box modeling, relying on salinity and color for calibration. In some cases, plumes reach the scale of peripheral arctic seas, and amplification is expected during upcoming decades. Conclusions are mapped from the Lena to other boreal discharges, and future research questions are outlined regarding the bonding type versus mass release as permafrost degrades. Dynamic aqueous organic coupling is recommended for polar system models, from headwaters to coastal diluent.
Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently ...identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection.
In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 "seeds" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social "contacts" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices.
Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds.
Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.
To explore acceptability of recruiting social contacts for HIV and sexually transmitted infection (STI) screening in Lilongwe, Malawi.
In this observational study, three groups of 'seed' patients ...were enrolled: 45 HIV-infected patients with STI, 45 HIV-uninfected patients with STI and 45 community controls, who were also tested for HIV as part of the study. Each seed was given five coupons and asked to recruit up to five social contacts to the STI clinic. Seeds were told the programme for contacts would include HIV testing, STI screening and general health promotion. Seeds were asked to return after 1 month to report on the contact recruitment process. Seeds received $2 for each successfully recruited contact.
Eighty-nine seeds (66%) returned for 1-month follow-up with no difference between the three seed groups (p=0.9). Returning seeds reported distributing most of their coupons (mean=4.1) and discussing each feature of the programme with most contacts-HIV testing (90%), STI screening (87%) and health promotion (91%). Seeds reported discussing their own HIV status with most contacts (52%), with a lower proportion of HIV-infected seeds discussing their HIV status (22%) than HIV-uninfected seeds (81%) or community seeds (64%) (p<0.001). Contact recruitment did not vary with socioeconomic status.
Most seeds distributed all coupons and reported describing all aspects of the programme to most contacts. Patients with STI are able to act as health promoters within their social networks and may be a critical link to increasing STI and HIV status awareness among high-risk groups.
There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify ...potential barriers and opportunities.
These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites.
Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved ≤ 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients).
The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease.
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