The case of Mary Mallon, an asymptomatic carrier who infected 51 people while working as a cook and laundress in New York in 1906-15, showed that Salmonella enterica serovar Typhi (S Typhi) is able ...to lurk in the gallbladder without overt clinical signs and spread enteric fever through person-to-person transmission.
Abstract Background Multidrug-resistant typhoid is a global health problem. Previous studies conducted in countries of Asia and Africa have identified a highly clonal, multidrug-resistant lineage of ...Salmonella enterica serovar Typhi ( S Typhi), known as H58. However, little is known about the emergence and geographical spread of the H58 clade. In this study, we have used whole-genome sequencing of a global collection of S Typhi to investigate this highly successful lineage. Methods We sequenced the whole-genome sequences of 1832 strains of S Typhi isolated between 1905 and 2013 (HiSeq platform, Illumina, San Diego, CA, USA). The isolates originated from 63 countries in six continents (Asia, Africa, North America, South America, Europe, and Oceania). The genomes of all 1832 S Typhi were mapped to the reference strain CT18 from Vietnam, and all single nucleotide changes were extracted and used to generate a maximum likelihood phylogeny of the whole collection. Transmission routes were also investigated with Bayesian analysis. The genomes were interrogated for the presence of plasmids and antimicrobial resistance genes. Long-read sequencing (PacBio platform, Pacific Biosciences, Menlo Park, CA, USA) was used to confirm the chromosomal location of resistance genes in representative isolates. Findings Phylogenetic reconstruction showed that the multidrug-resistant lineage H58 emerged approximately 30 years ago and has undergone clonal expansion resulting in a widespread global distribution, involving at least 20 countries across Asia, Africa, and Oceania. The analyses showed numerous transmission pathways by which S Typhi H58 is disseminating to many locations worldwide: our data provide evidence that a multidrug-resistant typhoid epidemic is moving across Eastern and Southern Africa. Comparative genomic analysis revealed that the H58 lineage has a distinct genetic profile. Furthermore, isolates from this lineage frequently carried a composite transposable element encoding multiple antimicrobial resistance determinants, which was found either in IncHI1 plasmids or integrated within the chromosome. Interpretation Our study highlights the urgent need for routine surveillance to detect epidemics and monitor fluctuations in the population structure of S Typhi. These data will facilitate public health measures, such as the effective use of antimicrobial agents and the introduction of vaccine programmes, and in doing so will help to address the significant burden of disease caused by typhoid. Funding VKW, DP, AJP, and GD were funded by the Wellcome Trust (098051). NAF was supported by a Wellcome Trust research fellowship (WT092152MA). NAF and this work were supported by a strategic award from the Wellcome Trust for the Malawi-Liverpool Wellcome Trust Clinical Research Programme (101113/Z/13/Z). KEH was supported by the National Health and Medical Research Council of Australia (fellowship 1061409) and the Victorian Life Sciences Computation Initiative (grant VR0082). SB is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/12/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the abstract.
Summary Background We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in ...children and adults. Methods We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com , number ISRCTN 53258327. Findings 844 patients with a median age of 16 (IQR 9–22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio HR of time to failure 0·86, 95% CI 0·40–1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68–4·68) in the chloramphenicol group and 3·90 days (3·58–4·27) in the gatifloxacin group (HR 1·06, 0·86–1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group. Interpretation Although no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events. Funding Wellcome Trust.
Background While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics ...in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. Objective The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. Study Design A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Results Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Conclusion Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function.
Empirical studies and surveillance projects increasingly assess and address potentially adverse psychological health outcomes from the stress of military operations, but no standards yet exist for ...common concept definitions, variable categories, and measures. This article reports the consensus recommendations of the federal interagency Operational Stress Working Group for common data elements to be used in future operational stress research and surveillance with the goal of improving comparability across studies. Operational stress encompasses more than just combat; it occurs everywhere service members and their families live and work. Posttraumatic stress is not the only adverse mental or behavioral health outcome of importance. The Operational Stress Working Group contends that a primary goal of operational stress research and surveillance is to promote prevention of adverse mental and behavioral outcomes, especially by recognizing the preclinical and subclinical states of distress and dysfunction that portend a risk for failure of role performance or future mental disorders. Recommendations for data elements are divided into 3 tiers: core, supplemental, and emerging, including variable domains and specific measures for assessing operational stressor exposures, stress outcomes, moderating factors, and mediating processes. Attention is drawn to the emerging construct of stress injury as a generic term for subclinical operational stress, and to emerging data elements addressing biological, psychological, and spiritual mediators of risk. Methodologies are needed for identifying preclinical and subclinical states of distress or dysfunction that are markers of risk for failure of role performance and future clinical mental disorders, so that targeted prevention interventions can be developed and evaluated.
Abstract Statement of problem Clinicians question when to evaluate for worn or loose implant-supported retainer screws to prevent possible clinical complications. Purpose The purpose of this study ...was to compare differences among initial and postdynamically loaded detorque values and identify physical structural changes of prosthetic retaining screws in a simulated implant-supported mandibular complete fixed prosthesis. Material and methods Nine groups and nonloaded controls comprising a 5-implant-supported, milled titanium framework were fabricated and assembled (screw torque 35 Ncm). Dynamic loading (20 to 220 N) was applied to simulate 2 years of oral function. After testing, screw detorque values were measured (ΔT, initial-detorque value). A scanning electron microscopic analysis of screw threads was used to assess physical changes. Data were analyzed by 2-way ANOVA to determine the influence of loading and implant position on ΔT (α=.05). Results ΔT values of loaded and nonloaded groups were compared separately at each implant position and showed a significant difference only for the implant in the central position ( P =.002). All positions were compared in terms of ΔT values separately for loaded and nonloaded conditions. A significantly higher ΔT was found in 1 cantilever area of the loaded group, whereas a significantly lower ΔT value was found in the central position in the nonloaded group. No statistically significant differences were found in physical changes between loading and nonloading or among implant positions. Conclusions When delivering a multiimplant supported prosthesis, the application of dynamic loading and the sequence in which implant screws are tightened could influence the subsequent detorque value of a screw; they have no effect on the physical appearance of screws after extended function.
Fatal consequences of freshwater pearl diving Phu, Nguyen Hoan, MD; Hoang Mai, Nguyen Thi, MD; Nghia, Ho Dang Trung, MD ...
Lancet,
01/2013, Volume:
381, Issue:
9861
Journal Article
Peer reviewed
Open access
Polymerase chain reaction (PCR) amplification targeting the 18s RNA gene was done retrospectively.1 The PCR amplicon was sequenced and confirmed to have 100% homology with the 18s RNA gene of ...Naegleria fowleri, which is the cause of primary amoebic meningoencephalitis. Within the central nervous system N fowleri amoebae cause an intense inflammatory reaction accompanied by necrosis and haemorrhage.3 Amoebic meningoencephalitis seems to be increasing in frequency with an expanding geographic footprint.4,5 Clinical and CSF findings are difficult to distinguish from bacterial meningitis.5 A history of freshwater exposure and symptoms such as the loss of the sense of smell should prompt consideration of the disease.4 The infection has a very high case-fatality rate and very few survivors have been documented.
We aimed to determine whether heart, stroke, and vascular disease (HSVD) prevalence and emergency primary evacuation (EPE), hospitalisation, and mortality differ by patient characteristics.
An ...Australian-wide incidence population based study, with prospective data collected form the 1 July 2019 to the 30 October 2020.
Indigenous Australians reported significantly higher prevalence of HSVD at 229.0 per-1000 as compared to 152.0 per-1000 non-Indigenous Australians: risk ratio 1.5 (95% CI 1.2-1.8). 583 remote patients received an EPE for HSVD, consisting of 388 (66.6%; 95% CI: 62.6-70.4) males and 195 (33.0%; 95% CI: 29.6-37.4) females. There were 289 (49.6%; 95% CI 45.4- 53.7) patients who identified as Indigenous, and 294 (50.4%; 95% CI 46.3- 54.6) as non-Indigenous. The mean Indigenous age during EPE was 48.0 (95% CI 45.9-50.1) years old, significantly lower than the non-Indigenous mean age of 55.6 (95% CI 53.8-57.4). Indigenous patients hospitalised for HSVD were younger, the majority younger than 65 years (n=21175; 73.7% 95% CI 73.2-74.2) as compared to non-Indigenous patients (n= 357654; 33.1% 95% CI 33.0-33.15). When adjusted for HSVD prevalence, remote Indigenous patients had a higher hospitalisation rate as compared to non-remote Indigenous patients (rate ratio: 1.6; 95% CI 1.3-2.0) and remote non-Indigenous patients (rate ratio: 1.2; 95% CI 1.0-1.5). More Indigenous patients died of HSVD before the age of 65 years (n=1875; 56.5% 95% CI 54.8-58.2) as compared to non-Indigenous patients (n= 16161; 10.6% 95% CI 10.45-10.8).
Indigenous Australians have a higher prevalence, and younger age during EPE, and hospitalisation for HSVD than non-Indigenous Australians.
This is a self/internally-funded study, with the lead organisation being the Royal Flying Doctor Service (RFDS) of Australia. For the duration of the study period, the RFDS provided in-kind support including one full-time equivalent (FTE) and resources (office space, computer, research software, and office equipment). There was no external funding source that had a role in study design or data analysis or interpretation.
Statement of problem Previous implant torque evaluation did not determine if the target value fell within a confidence interval for the population mean of the test groups, disallowing determination ...of wheter a specific type of wrench met a standardized goal value. Purpose The purpose of this study was to measure both the accuracy and precision of 2 different configurations (spring style and peak break) of as-received implant torque wrenches and compare the measured values to manufacturer-stated values. Material and methods Ten wrenches from 4 manufacturers, representing a variety of torque-limiting mechanisms and specificity of use (with either a specific brand or universally with any brand of implant product). Drivers were placed into the wrench, and tightening torque was applied to reach predetermined values using a NIST-calibrated digital torque wrench. Five replications of measurement were made for each wrench and averaged to provide a single value from that instrument. The target torque value for each wrench brand was compared to the 95% confidence interval for the true population mean of measured values to see if it fell within the measured range. Results Only 1 wrench brand (Nobel Biocare) demonstrated the target torque value falling within the 95% confidence interval for the true population mean. For others, the targeted torque value fell above the 95% confidence interval (Straumann and Imtec) or below (Salvin Torq). Conclusions Neither type of torque-limiting mechanism nor designation of a wrench to be used as a dedicated brand-only product or to be used as a universal product on many brands affected the ability of a wrench to deliver torque values where the true population mean included the target torque level.
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