Changes In Clinical Treatment Research Articles

Rapid inference of antibiotic resistance and susceptibility for Klebsiella pneumoniae by clinical shotgun metagenomic sequencing

ObjectivesThe study aimed to develop a genotypic antimicrobial resistance testing method for Klebsiella pneumoniae using metagenomic sequencing data. MethodsWe utilized Lasso regression on assembled genomes to identify genetic resistance determinants for six antibiotics (Gentamicin, Tobramycin, Imipenem, Meropenem, Ceftazidime, Trimethoprim/Sulfamethoxazole). The genetic features were weighted, grouped into clusters to establish classifier models. Origin species of detected antibiotic resistant gene (ARG) was determined by novel strategy integrating “possible species,” “gene copy number calculation” and “species-specific kmers.” The performance of the method was evaluated on retrospective case studies. ResultsOur study employed machine learning on 3928 K. pneumoniae isolates, yielding stable models with AUCs > 0.9 for various antibiotics. GenseqAMR, a read-based software, exhibited high accuracy (AUC 0.926–0.956) for short-read datasets. The integration of a species-specific kmer strategy significantly improved ARG-species attribution to an average accuracy of 96.67%. In a retrospective study of 191 K. pneumoniae-positive clinical specimens (0.68–93.39% genome coverage), GenseqAMR predicted 84.23% of AST results on average. It demonstrated 88.76–96.26% accuracy for resistance prediction, offering genotypic AST results with a shorter turnaround time (mean ± SD: 18.34 ± 0.87 hours) than traditional culture-based AST (60.15 ± 21.58 hours). Furthermore, a retrospective clinical case study involving 63 cases showed that GenseqAMR could lead to changes in clinical treatment for 24 (38.10%) cases, with 95.83% (23/24) of these changes deemed beneficial. ConclusionsIn conclusion, GenseqAMR is a promising tool for quick and accurate AMR prediction in Klebsiella pneumoniae, with the potential to improve patient outcomes through timely adjustments in antibiotic treatment.

Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration.

OBJECTIVEMaturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.RESEARCH DESIGN AND METHODSWe evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines.RESULTSOf 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006).CONCLUSIONSBy comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.

Monogenic Diabetes in the Progress for Diabetes Genetics in Youth (ProDiGY) Collaboration

Monogenic diabetes, including maturity-onset diabetes of the young (MODY), is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis can result in a change in clinical treatment and impacts prediction of complications and familial risk. Clinical algorithms can select individuals for genetic testing; however, up to half of youth with MODY do not meet clinical criteria. Other barriers also limit access to genetic testing. To assess the prevalence of MODY in youth with a clinical diagnosis of type 2 diabetes, we evaluated whole-exome sequence data from ProDiGY, a collaboration of the TODAY, SEARCH for Diabetes in Youth, and T2D-GENES studies. Focusing on 14 genes previously identified as causal for MODY (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1) we considered patients to have MODY if they carried one or more variants classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. We found 77 of 3650 patients carried an LP/P variant in HNF4A (14 individuals), GCK (22), HNF1A (32), PDX1 (4), INS (3), and PAX4 (2). Compared to those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 0.3 vs. 13.6 ± 0.1, P=0.01) and lower fasting C-peptide levels (3.0 ± 0.2 vs. 4.5 ± 0.1, P=0.0001), although for both measures, the range of values overlapped between the two groups. Youth with MODY were less likely to have hypertension (6.9% vs. 18.2%, P=0.03) and less likely to be on insulin (32.0% vs. 51.1%, P=0.001). Parental history of diabetes was not significantly different. MODY was found in all race/ethnic groups. Using a comprehensive set of MODY genes, we identified MODY in 2% of youth with clinically diagnosed type 2 diabetes; in 88% (n=68) the specific diagnosis would direct management. While these individuals differed significantly on several clinical characteristics, no criterion reliably separated the two groups. Further study is needed to find ideal criteria to select individuals for genetic testing. Disclosure J. Todd: None. J.W. Kleinberger: None. S. Srinivasan: None. S.E. Tollefsen: None. L.L. Levitsky: Consultant; Self; Eli Lilly and Company. L.E.L. Katz: None. J.B. Tryggestad: None. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. G. Imperatore: None. J.M. Lawrence: None. C. Pihoker: None. J. Divers: None. J. Flannick: None. D. Dabelea: None. J.C. Florez: Consultant; Self; Intarcia Therapeutics, Inc.. Consultant; Spouse/Partner; Santen. T.I. Pollin: Research Support; Self; Regeneron Pharmaceuticals, Inc..

Appropriate use of echocardiography and relation to clinical decision making in both inpatients and outpatients in a developing country.

Use of echocardiography (echo) has exponentially increased in recent decades. Concerned about this scientific society developed appropriate use criteria (AUC). Clinical management still suffers geographical variations, and no objective data are available about echo AUC in developing countries. We aimed to evaluate (1) the appropriateness of referrals and (2) their relation to changes in clinical decision management. Prospective analysis of referrals from January to December 2014. Appropriateness and endpoints analyzed in different time points from medical archives. (1) change in the diagnosis, (2) indication for another method to complete the diagnosis, (3) change in clinical treatment, (4) indication for a treatment intervention, or (5) no change in management. Descriptive statistical analysis, Fisher's or chi-square tests, and Cox regression used as appropriate (significance if P<.05). One thousand one hundred referrals were analyzed (55.5±16.1years, 44.6% male). 80.5% of referrals were appropriate (A), 11.2% "Rarely Appropriate" (RA), and 8.3% "May Be Appropriate" (MBA). Proportion of (A) did not differ between modalities (TTE-80.5% vs TEE-87.7% vs STR-81.2%, P=.67). (A) referrals were more related to clinical decision than (RA)+(MBA) (38.9% [A] vs 15% [RA]+[MBA], P<.001). The most frequent clinical indications of (RA) and (MBA) TTE were reevaluation of ventricular function without clinical change (AUC 10 and 11) and search of infectious endocarditis when low clinical probability (53). In a developing country, appropriateness of echo was similar to the United States and Europe. However, a significant proportion of referrals were still (RA) or (MBA), with no effect in clinical management. Controlling referrals 10, 11, and 53 can optimize echo use in developing countries.

Evaluation of treatment changes following electronic consultation to a pharmacist-run urine drug testing service in a veterans healthcare system.

In 2013, the North Florida/South Georgia Veterans Healthcare System established a pharmacist-run urine drug testing (UDT) electronic consultation (e-consult) service to assist providers with interpretation of this useful yet complex clinical tool. This pilot study aimed to classify clinical treatment changes implemented following e-consult to a pharmacist-run UDT service and analyze factors limiting pharmacist intervention postconsultation. One hundred forty-three e-consults were completed in the 2-year study period including interpretation of 190 UDT results classified as expected, unexpected, or not necessarily inappropriate based on prescription profile at time of urine immunoassay test. Preconsult evaluation revealed that in more than 70 percent of cases, no confirmatory testing was ordered on the sample in question by the requesting provider. Of the 28 percent of UDT results classified as unexpected, 32 percent identified the presence of an illicit substance. Completed e-consults provided either education-based (informative) or actionbased (decisive) recommendations. In 50 percent of the cases where unexpected substances were identified, pharmacy specialists recommended immediate action to be taken by the provider. Subsequent review indicates that timely documentation of postconsultation action by requesting provider was only present in 32 percent of this group. Continued efforts toward an improved understanding of UDT utility by providers, along with expedited placement of e-consult following urine collection, may allow for increased implementation of pharmacist interventions and lead to more optimal use of this clinical tool.

Inter- and intraobserver agreement in computed tomography enterography in inflammatory bowel disease.

AIMTo evaluate intra- and interobserver agreement in imaging features in inflammatory bowel disease and comparison with fecal calprotectin (FC) levels.METHODSOur institutional computed tomography enterography (CTE) database was retrospectively queried to identify patients who underwent CTE from January 2014 to June 2015. Patient inclusion criteria were confirmed inflammatory bowel disease (IBD) and FC collected < 4 mo after CTE without any change in clinical treatment or surgical treatment during this interval. The exclusion criterion was poor image quality. Two blinded abdominal radiologists, with 12 and 3 years of experience analyzed the CTE regarding localization (small bowel, colonic, both, or no disease detected); type of IBD (inflammatory, stenosing, fistulizing, > 1 pattern, or normal); and signs of active disease (present or absent). In 42 of 44 patients evaluated, routine CTE reports were made by one of the readers who re-evaluated the CTEs ≥ 6 mo later, to determine the intraobserver agreement. FC was considered a sign of disease activity when it was higher than 250 μg/g.RESULTSForty-four patients with IBD (38 with Crohn’s disease and 6 with ulcerative colitis) were included. There was a moderate interobserver agreement regarding localization of IBD (κ = 0.540), type of disease (κ = 0.410) and the presence of active signs in CTE (κ = 0.419). There was almost perfect intraobserver agreement regarding localization, type and signs of active disease in IBD. The κ values were 0.902, 0.937 and 0.830, respectively. After a consensus between both radiologists regarding inflammatory activity in CTE, we found that 24 (85.7%) of 28 patients who were classified with active disease had elevated FC, and six (37.5%) of 16 patients without inflammatory activity in CTE had elevated FC (P = 0.003). The correlation between elevated FC and the presence of active disease in CTE was significant (κ = 0.495, P = 0.001).CONCLUSIONWe found almost perfect intraobserver and moderate interobserver agreement in the signs of active disease in CTE with concurrence of high FC levels.

Improved Diagnostic Testing and Malaria Treatment Practices in Zambia

Improving the accuracy of malaria diagnosis with rapid antigen-detection diagnostic tests (RDTs) has been proposed as an approach for reducing overtreatment of malaria in the current era of widespread implementation of artemisinin-based combination therapy in sub-Saharan Africa. To assess the association between use of microscopy and RDT and the prescription of antimalarials. Cross-sectional, cluster sample survey, carried out between March and May 2006, of all outpatients treated during 1 working day at government and mission health facilities in 4 sentinel districts in Zambia. Proportions of patients undergoing malaria diagnostic procedures and receiving antimalarial treatment. Seventeen percent of the 104 health facilities surveyed had functional microscopy, 63% had RDTs available, and 73% had 1 or more diagnostics available. Of patients with fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%) treated in health facilities with malaria diagnostics were tested and 44.6% had positive test results. Of patients with negative blood smear results, 58.4% (95% CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI, 16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did not have diagnostic tests done, 65.9% were also prescribed antimalarials. In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed to a large proportion of febrile patients with a positive diagnostic test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%-100.0%]), but also to some of those with a negative diagnostic test result (blood smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]). Despite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials. Provision of new tools to reduce inappropriate use of new expensive antimalarial treatments must be accompanied by a major change in clinical treatment of patients presenting with fever but lacking evidence of malaria infection.

Handling Difficult Family Situations: Practical Approaches

Some of the most challenging calls that attorneys advising health care providers receive involve situations in which care of a resident is not problematic, but relations with the resident’s family or responsible party have grown intolerable. Providers are accustomed to families with high expectations. Issues can arise from how family members express those expectations. Sometimes, particular family members bring to their interaction with long-term care providers, including both facilities and clinical staff, behaviors that can only be characterized as unthinking, hostile, or rude. This may stem from frustration with the services rendered or with the nature of the resident’s condition, but it can also result from longstanding, interpersonal issues between the resident and the family member(s) that are exacerbated by the resident’s institutionalization, and the facility staff become the target of these issues rather than the resident. This can include demands for changes in clinical treatment with which the staff would otherwise disagree. Fearful of complaints, either to superiors or regulatory agencies, or of litigation, staff may simply acquiesce to demands. Or they may find themselves in a seemingly endless number of exchanges from which closure or resolution can seem fruitless. It is important to recognize the legal constraints within which facilities operate and to which they are subject. Staff members need to e

Biomechanics of External Fixation of Distal Tibial Extra-Articular Fractures

To compare the mechanical stability of external fixation with and without spanning of the ankle joint with a foot plate in an in vitro model of extra-articular distal tibia fractures. A laboratory investigation was performed to evaluate the mechanical behavior of external fixation of extra-articular distal tibia fractures using a fixator with and without a foot plate. Ten fresh-frozen lower extremities (5 pairs) with a simulated OTA 43-A3.3 fracture were stabilized with an Ilizarov hybrid fixator with and without a foot plate. All mechanical testing was performed with a servohydraulic test frame (MTS Bionix 858, Minneapolis, MN). Deformation characteristics as a function of load were compared for an Ilizarov fixator with and without a foot plate under identical conditions of forefoot loading from 0 to 100 N. Relative interfragmentary motions (vertical and horizontal translations and rotation) were measured. There was significantly more vertical translation (2.57 +/- 0.97 mm vs. -0.83 +/- 0.64 mm) and angular displacement (4.49 +/- 0.45 degrees vs. -1.15 +/- 0.61 degrees ) of the distal fragment in the arrangement without a foot plate compared with the construct with a foot plate. The anterior translation of the distal fragment was similar with (1.12 +/- 0.98 mm) and without a foot plate (1.19 +/- 1.23 mm). This study supports the mechanical importance of spanning of the ankle with a foot plate in most cases of external fixation for unstable extra-articular and periarticular distal tibia fractures. Further studies are needed to validate these results before widespread changes in clinical treatment can be recommended.

HUNDREDTH VOLUME

The first journal was published just after the end of Queen Victoria's reign. Stability had ruled for forty years and from Britain obstetricians turned to Europe for intellectual and technical stimulation; American medicine followed rather than led. It was a brave group of doctors who in 1902 put up the money to start a journal in what was a small speciality in a small island. Now, with numbering not being precisely annual, we have reached the hundredth volume and it is time to take stock. The world is a more unstable place. European medicine has lost its lead and Americans fuel the fires. In Britain, the subject of Obstetrics and Gynaecology is under pressure from educationalists and politicians, from the altruists on one hand who tell us we are too technical and not human enough to the epidemiological purists on the other hand who berate us for not following the results of randomised controlled trials and of being too human. The British Journal of Obstetrics and Gynaecology has reflected all these changes and Sir John Peel traces them in his review of the history of the Journal (p. 2). We reproduce also what the contemporary British Medical Journal and the Lancet said about our first number (p. 9). The style of our Journal follows fashion like any other dynamic organisation. The first cover, which we have reproduced, is overcrowded in heavy Gothic style to get every possible fact on to the front page. It resembles the shop window of the village grocer. The current cover is startlingly simple and reflects the design ideas of the 1990s, looking more like an Italian racing motor car. Between the covers, the more anecdotal events of clinical practice have given way to objectively judged scientific material. We started the century with one man's account of a hundred cases of women with fibroids and end with randomised placebo controlled trials assessing pharmacological marvels. We reproduce two previous Journal articles, on ergometrine by Chassar Moir and C. S. Russell and ultrasound by Ian Donald; we consider these amongst the most important in the last ninety years, for each led to major changes in practice. To choose them we read widely in the previous ninety-nine volumes and selection was difficult, being dictated more by the pages available than the number of seminal articles. It was interesting, however, to note that events such as the early use of antibiotics for puerperal pyrexia or of gynaecological laparoscopy had their first publications in other journals and only after a couple of years was material available to the British Journal of Obstetrics and Gynaecology. Perhaps this reflects the more drawn out processing of articles in a monthly journal; the immediacy of the weekly journals influenced authors keen to see their innovations in print more promptly. The Journal editors have distanced their protegé from the wider social and political world; we searched in vain for comment on the foundation of the College of Obstetricians and Gynaecologists, the Second World War or the introduction of the National Health Service. Even the obituary columns were stopped and the Journal has kept to the science of Obstetrics and Gynaecology within its covers. For the future we hope that the British Journal of Obstetrics and Gynaecology will reflect the world of Obstetrics, its science, its work and the Royal College which guides and guards British Obstetrics. We will keep the scientific standards at the high levels to which previous editors have raised them and add other material slowly during the next years. The changes that we will reflect in Obstetrics and Gynaecology before the turn of the century are likely to be greater in the practice of the subject than any other that has occurred in the last ninety years. It is right therefore, that the Journal should have some reporting of these, rather than just the scientific measurement of Obstetrics and Gynaecology. As well as changes in clinical treatment, there will be much alteration in the management of obstetricians. Education, service commitments and work patterns will be altered so much in the next few years that the Journal should rightly keep its readers, in Britain and beyond, aware of some of these changes in which the Royal College is taking an active role. We look towards exciting days; the science of Obstetrics and Gynaecology has bloomed actively and will go on so doing, whilst the art of the subject will expand also. Both of these will take place inside the changes which society will provide. These are in two parts, the micro-environment of the hospitals and universities within which we work and the larger environment of the community we serve. All these variables need to be reflected in a balanced journal.

Enhanced detection of vesicoureteral reflux in infants and children with use of cyclic voiding cystourethrography.

Cyclic voiding cystourethrography (VCUG) was prospectively evaluated to determine its ability to demonstrate vesicoureteral reflux (VUR) in children whose VCUG results were initially negative. The authors also assessed the effect of change in the patient's position on the detection of VUR. Seventy-seven children younger than 3 years of age, with negative results from a VCUG study performed while they were supine, underwent a second cycle of bladder filling after they were placed prone (group 1). Sixty-five children who were also younger than 3 years of age and had negative results from an initial VCUG examination performed in the usual supine position underwent a second cycle of bladder filling, which was also performed with the patient supine (group 2). VUR occurred in three children (4%) in group 1 and in eight (12%) in group 2. Most children (68.8%) in the two groups combined had grade II reflux. Cyclic VCUG increased detection of VUR, which led to a change in clinical treatment. Prone positioning did not enhance detection of VUR to the same degree as did multiple studies performed with the patient supine.