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1.
Am J Transplant ; 24(4): 653-668, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37977229

RESUMO

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.


Assuntos
Transplante de Órgãos , Pneumocystis carinii , Pneumonia por Pneumocystis , Feminino , Humanos , Pessoa de Meia-Idade , Europa (Continente) , Glucocorticoides/uso terapêutico , Transplante de Órgãos/efeitos adversos , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/etiologia , Estudos Retrospectivos , Transplantados , Masculino , Idoso
2.
Am J Gastroenterol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38299616

RESUMO

INTRODUCTION: Absent contractility on high-resolution manometry (HRM) defines severe hypomotility but needs distinction from achalasia. We retrospectively identified achalasia within absent contractility using HRM provocative maneuvers, barium esophagography, and functional lumen imaging probe (FLIP). METHODS: Adult patients with absent contractility on HRM during the 4-year study period were eligible for inclusion. Inadequate studies, achalasia after therapy, or prior foregut surgery were exclusions. Upright integrated relaxation pressure (IRP) >12 mm Hg, panesophageal pressurization, and/or elevated IRP on multiple rapid swallows and rapid drink challenge (RDC) were considered abnormal. Esophageal barium retention and abnormal esophagogastric junction distensibility index (<2.0 mm 2 /mm Hg) on FLIP defined achalasia. Clinical, endoscopic, and motor characteristics of patients with achalasia were compared with absent contractility without obstruction. RESULTS: Of 164 patients, 20 (12.2%) had achalasia (17.9% of 112 patients with adjunctive testing), while 92 did not, and 52 did not undergo adjunctive tests. Achalasia was diagnosed regardless of IRP value, but the median supine IRP was higher (odds ratio 1.196, 95% confidence interval 1.041-1.375, P = 0.012). Patients with achalasia were more likely to present with dysphagia (80.0% vs 35.9%, P < 0.001), with obstructive features on HRM maneuvers (83.3% vs 48.9%, P = 0.039), but lower likelihood of GERD evidence (20.0% vs 47.3%, P = 0.027) or large hiatus hernia (15.0% vs 43.8%, P = 0.002). On multivariable analysis, dysphagia presentation ( P = 0.006) and pressurization on RDC ( P = 0.027) predicted achalasia, while reflux and presurgical evaluations and lack of RDC obstruction predicted absent contractility without obstruction. DISCUSSION: Despite HRM diagnosis of absent contractility, achalasia is identified in more than 1 in 10 patients regardless of IRP value.

3.
Am J Gastroenterol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297514

RESUMO

INTRODUCTION: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome. METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to antireflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from 2 centers (Europe and the United States) constituted the developmental cohort, while 2 separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics analysis determined performance of the Lyon score in predicting treatment response. RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an area under the curve (AUC) of 0.819 in predicting 50% symptom improvement ( P < 0.001) on receiver operating characteristics, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, P < 0.001), mean nocturnal baseline impedance (AUC 0.785, P < 0.001), and reflux episodes (AUC 0.764, P < 0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, P < 0.001) and Asian validation cohorts (AUC 0.637, P < 0.001) and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts. DISCUSSION: The novel Lyon score segregates reflux phenotypes and identifies likelihood of symptom response from antireflux therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39259571

RESUMO

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) can deliver extended parenteral treatment of fungal infections in an ambulatory setting, whilst minimizing treatment burden and cost. The extended dosing interval of rezafungin may potentiate the benefits of OPAT. METHODS: This retrospective cohort study includes all adult patients who received echinocandin therapy in a large OPAT programme between 2012 and 2022. Patient characteristics, treatment and outcomes were studied. Data were analysed to determine the effects of replacing daily dosing with weekly dosing of echinocandin. RESULTS: Across the study period, 11% (44/386) of all patients in our Health Service treated with ≥7 days of echinocandin were managed via OPAT. All were Candida and related 'yeast-like' species infections. Nakaseomyces glabrata (20/41; 49%) was the most common pathogen, fungaemia the most common presentation (17/41; 41%) and azole resistance the most frequent indication for echinocandin use (21/41; 51%).In total, 633 days of echinocandin were administered as OPAT. Thirteen patients (13/41; 32%) received concurrent parenteral antibacterials. Treatment success was achieved in 30/41 (73%) patients. If daily echinocandin dosing was replaced with weekly dosing, a potential 52% (633 to 326) reduction in the total number of treatments (for any therapy) delivered by the OPAT team is possible. The ongoing need for daily antibacterial administration mitigated the benefit in some of this cohort. CONCLUSIONS: Echinocandin therapy can be safely delivered via OPAT with outcomes equivalent to bed-based care. The extended dosing interval of rezafungin will allow for a substantial reduction in the number of treatments required across the patient cohort.

5.
J Clin Gastroenterol ; 58(1): 24-30, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729406

RESUMO

BACKGROUND AND AIMS: Bariatric surgical options in obese patients include sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB), which may not be equivalent in risk of postoperative reflux symptoms. We evaluated risk and predictive factors for postbariatric surgery reflux symptoms. METHODS: Patients with obesity evaluated for bariatric surgery over a 15-month period were prospectively followed with validated symptom questionnaires (GERDQ, dominant symptom index: product of symptom frequency and intensity from 5-point Likert scores) administered before and after SG and RYGB. Esophageal testing included high-resolution manometry in all patients, and ambulatory reflux monitoring off therapy in those with abnormal GERDQ or prior reflux history. Univariate comparisons and multivariable analysis were performed to determine if preoperative factors predicted postoperative reflux symptoms. RESULTS: Sixty-four patients (median age 49.0 years, 84% female, median BMI 46.5 kg/m 2 ) fulfilled inclusion criteria and underwent follow-up assessment 4.4 years after bariatric surgery. Baseline GERDQ and dominant symptom index for heartburn were significantly higher in RYGB patients ( P ≤0.04). Despite this, median GERDQ increased by 2 (0.0 to 4.8) following SG and decreased by 0.5 (-1.0 to 5.0) following RYGB ( P =0.02). GERDQ became abnormal in 43.8% after SG and 18.8% after RYGB ( P =0.058); abnormal GERDQ improved in 12.5% and 37.5%, respectively ( P =0.041). In a model that included age, gender, BMI, acid exposure time, and type of surgery, multivariable analysis identified SG as an independent predictor of postoperative heartburn (odds ratio 16.61, P =0.024). CONCLUSIONS: Despite preferential RYGB when preoperative GERD was identified, SG independently predicted worsening heartburn symptoms after bariatric surgery.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Azia/diagnóstico , Azia/etiologia , Triagem , Estudos Retrospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Obesidade/cirurgia , Gastrectomia/efeitos adversos , Resultado do Tratamento
6.
J Pediatr Gastroenterol Nutr ; 79(3): 541-549, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39010786

RESUMO

OBJECTIVES: Ineffective esophageal motility (IEM) on high-resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. METHODS: Clinical and manometric characteristics of children undergoing esophageal HRM during 2021-2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. RESULTS: Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p = 0.002), but other adjunctive testing was similar. Among 101 patients with follow-up, symptomatic cohorts declined in both groups in relation to the initial presentation (p > 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p ≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow-up in IEM (64.0% vs. 39.1%, p = 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p = 0.017). CONCLUSIONS: IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes.


Assuntos
Transtornos da Motilidade Esofágica , Manometria , Humanos , Feminino , Masculino , Adolescente , Estados Unidos/epidemiologia , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/fisiopatologia , Transtornos da Motilidade Esofágica/terapia , Transtornos da Motilidade Esofágica/epidemiologia , Manometria/métodos , Criança , Prevalência , Estudos Retrospectivos , Pré-Escolar , Esôfago/fisiopatologia , Gastroenterologia/métodos
7.
Curr Gastroenterol Rep ; 26(4): 115-123, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38324172

RESUMO

PURPOSE OF REVIEW: Artificial intelligence (AI) is a broad term that pertains to a computer's ability to mimic and sometimes surpass human intelligence in interpretation of large datasets. The adoption of AI in gastrointestinal motility has been slower compared to other areas such as polyp detection and interpretation of histopathology. RECENT FINDINGS: Within esophageal physiologic testing, AI can automate interpretation of image-based tests, especially high resolution manometry (HRM) and functional luminal imaging probe (FLIP) studies. Basic tasks such as identification of landmarks, determining adequacy of the HRM study and identification from achalasia from non-achalasia patterns are achieved with good accuracy. However, existing AI systems compare AI interpretation to expert analysis rather than to clinical outcome from management based on AI diagnosis. The use of AI methods is much less advanced within the field of ambulatory reflux monitoring, where challenges exist in assimilation of data from multiple impedance and pH channels. There remains potential for replication of the AI successes within esophageal physiologic testing to HRM of the anorectum, and to innovative and novel methods of evaluating gastric electrical activity and motor function. The use of AI has tremendous potential to improve detection of dysmotility within the esophagus using esophageal physiologic testing, as well as in other regions of the gastrointestinal tract. Eventually, integration of patient presentation, demographics and alternate test results to individual motility test interpretation will improve diagnostic precision and prognostication using AI tools.


Assuntos
Acalasia Esofágica , Transtornos da Motilidade Esofágica , Humanos , Inteligência Artificial , Transtornos da Motilidade Esofágica/diagnóstico , Acalasia Esofágica/diagnóstico , Manometria/métodos
8.
Dig Dis Sci ; 69(5): 1714-1721, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38528208

RESUMO

BACKGROUND: The post-reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate to neutralize residual distal esophageal mucosal acidification. AIMS: To determine if reduced saliva production and esophageal body hypomotility would compromise PSPW-induced pH recovery in the distal esophagus. METHODS: In this multicenter retrospective cross-sectional study, patients with confirmed Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified. Patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period. Acid exposure time, numbers of reflux episodes and PSPW, pH recovery with PSPW, and HRM metrics were extracted. Univariate comparisons and multivariable analysis were performed to determine predictors of pH recovery with PSPW. RESULTS: Among Sjogren's syndrome (n = 34), scleroderma/MCTD (n = 14), and comparison patients with reflux symptoms (n = 96), the scleroderma/MCTD group had significantly higher AET, higher prevalence of hypomotility, lower detected reflux episodes, and very low numbers of PSPW (p ≤ 0.004 compared to other groups). There was no difference in pH-impedance metrics between Sjogren's syndrome, and comparison patients (p ≥ 0.481). Proportions with complete pH recovery with PSPW was lower in Sjogren's patients compared to comparison reflux patients (p = 0.009), predominantly in subsets with hypomotility (p < 0.001). On multivariable analysis, diagnosis of Sjogren's syndrome, scleroderma/MCTD or neither (p = 0.014) and esophageal hypomotility (p = 0.024) independently predicted lack of complete pH recovery with PSPW, while higher total reflux episodes trended (p = 0.051). CONCLUSIONS: Saliva production and motor function are both important in PSPW related pH recovery.


Assuntos
Monitoramento do pH Esofágico , Esôfago , Refluxo Gastroesofágico , Peristaltismo , Saliva , Síndrome de Sjogren , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/diagnóstico , Estudos Transversais , Peristaltismo/fisiologia , Síndrome de Sjogren/fisiopatologia , Síndrome de Sjogren/metabolismo , Saliva/metabolismo , Idoso , Esôfago/fisiopatologia , Esôfago/metabolismo , Manometria , Deglutição/fisiologia , Concentração de Íons de Hidrogênio , Adulto , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/metabolismo
9.
Intern Med J ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39387620

RESUMO

BACKGROUND: Multidisciplinary endocarditis team (MDET) management is supported by current evidence and recommended in international society guidelines. The extent to which this recommendation has been implemented in Australian centres and the attitudes, barriers and facilitators of this model are unclear. AIM: To describe current infective endocarditis (IE) models of care in Australian specialist referral centres and evaluate facilitators, barriers and attitudes towards MDET implementation. METHODS: Aims were addressed using two online surveys. Survey 1 audited IE models of care and was distributed to infectious disease physicians at specialist referral centres. Survey 2 assessed barriers, facilitators and attitudes towards MDETs and was distributed via societal email listings. RESULTS: From 56 identified cardiac surgery centres, survey 1 received 47 responses (84%). A total of 28% (13/47) of participating institutions had an existing MDET. A total of 85% (11/13) of MDETs were in public hospitals and 85% (11/13) were in high IE volume centres. Survey 2 had 109 respondents from seven specialties. Attitudes towards MDET implementation were generally favourable. Identified barriers to MDET implementation included a lack of funding, resources, expertise, time and collaboration. Facilitators included strong leadership, engagement from key stakeholders and tangible benefits. CONCLUSIONS: Even though it is recommended in international guidelines, the MDET model is used by less than one-third of Australian specialist referral centres. Stakeholders in IE care have generally favourable attitudes towards MDET implementation but cite a lack of resources, funding, collaboration and time as barriers to this. Dedication of financial and administrative support and leadership from key stakeholders are required to increase MDET utilisation.

10.
Clin Gastroenterol Hepatol ; 21(7): 1761-1770.e1, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36270615

RESUMO

BACKGROUND & AIMS: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. CLINICALTRIALS: gov ID: NCT04813029.


Assuntos
Refluxo Gastroesofágico , Hérnia Hiatal , Adulto , Humanos , Perna (Membro)/patologia , Refluxo Gastroesofágico/patologia , Junção Esofagogástrica/patologia , Esfíncter Esofágico Inferior , Manometria/métodos
11.
Am J Gastroenterol ; 118(12): 2148-2156, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37335154

RESUMO

INTRODUCTION: Sleeve gastrectomy (SG) results in persistent or de novo reflux more often than Roux-en-Y gastric bypass (RYGB). We investigated pressurization patterns in the proximal stomach on high-resolution manometry (HRM) to determine associations with reflux after SG. METHODS: Patients undergoing HRM and ambulatory pH-impedance monitoring after SG and RYGB over a 2-year period (2019-2020) were included. For each included patient, 2 symptomatic control patients with HRM and pH-impedance monitoring for reflux symptoms were identified within the same time frame; 15 asymptomatic healthy controls with HRM studies were also studied. Concurrent myotomy and preoperative diagnosis of obstructive motor disorders were exclusions. Conventional HRM metrics, esophagogastric junction (EGJ) pressures, contractile integral (EGJ-CI), acid exposure time (AET), and reflux episode numbers were extracted. Intragastric pressure was sampled at baseline, during swallows, and with straight leg raise maneuver, and compared with intraesophageal pressure and reflux burden. RESULTS: Patient cohorts included 36 SG patients, 23 RYGB patients, 113 symptomatic controls, and 15 asymptomatic controls. While both SG and RYGB patients pressurized the stomach during swallows and straight leg raise, SG patients had higher AET (median 6.0% vs 0.2%), reflux episode numbers (median 63.0 vs 37.5), and baseline intragastric pressure (median 17.3 mm Hg vs 13.1 mm Hg) ( P < 0.001). SG patients also had lower trans-EGJ pressure gradients when reflux episodes were >80 or AET was >6.0% ( P = 0.018 and 0.08, respectively, compared with no pathologic reflux). On multivariable analysis, SG status and low EGJ-CI independently associated with AET and reflux episode numbers ( P ≤ 0.04). DISCUSSION: Impaired EGJ barrier function and proximal gastric pressurization after SG are associated with gastroesophageal reflux, especially during strain maneuvers.


Assuntos
Esofagite Péptica , Derivação Gástrica , Refluxo Gastroesofágico , Obesidade Mórbida , Humanos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etiologia , Junção Esofagogástrica/patologia , Gastrectomia/métodos , Manometria/métodos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos
12.
Am J Gastroenterol ; 118(11): 2071-2074, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37307572

RESUMO

INTRODUCTION: Hiatus hernia is characterized by axial separation between the lower esophageal sphincter and the crural diaphragm, and higher reflux burden. Impact on reflux is unclear if such separation is intermittent rather than persistent. METHODS: Reflux burden off antisecretory therapy was compared between no hernia (n = 357), intermittent hernia (n = 42), and persistent hernia (n = 155) after review of consecutive high-resolution manometry and reflux monitoring studies. RESULTS: Proportions with pathologic acid exposure was similar between intermittent and persistent hernia (45.2% vs 46.5%, respectively), and both were significantly different from no hernia (28.7%, P ≤ 0.002). DISCUSSION: Intermittent hiatus hernias are clinically relevant in gastroesophageal reflux pathophysiology.


Assuntos
Refluxo Gastroesofágico , Hérnia Hiatal , Humanos , Hérnia Hiatal/complicações , Refluxo Gastroesofágico/complicações , Diafragma/patologia , Esfíncter Esofágico Inferior , Manometria
13.
J Antimicrob Chemother ; 78(3): 599-612, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36691839

RESUMO

BACKGROUND: Beta-lactam antibiotics are the mainstay of therapy for most bacterial causes of infective endocarditis (IE). Traditionally considered as agents with a broad therapeutic index, there is increasing recognition that standard doses may be subtherapeutic or toxic in critically ill patients. Optimizing therapy for efficacy requires a defined pharmacokinetic (PK)/pharmacodynamic (PD) target associated with clinical and microbiological cure. OBJECTIVES: To elucidate the factors that influence beta-lactam PK and PD variability in IE and to examine optimal PK/PD target parameters for therapy. METHODS: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical and laboratory in vivo animal or human studies examining PK and/or PD of beta-lactam antibiotics in IE were eligible. Ovid MEDLINE, Embase and Cochrane Central Registry were searched using defined terms. The Office of Health Assessment and Translation (OHAT) tool was used for assessing risk of bias. RESULTS: From 2677 abstracts, 62 articles were selected for review and synthesis, comprising: 45 animal studies investigating the broad categories of beta-lactam diffusion into vegetations, PK/PD determinants of outcome, mode of antibiotic delivery and synergistic impact of agents; and 17 human studies totalling 347 participants. Findings supported the importance of time-dependent killing for beta-lactams but heterogeneous data limited the determination of an optimal PK/PD target for IE treatment. CONCLUSION: Beta-lactam PK and PD in endocarditis are variable and specific to the particular antibiotic-organism combination. Time-dependent killing is important, consistent with non-endocarditis studies, but there is little agreement on optimal drug exposure. Clinical studies examining PK/PD targets in endocarditis are required to further inform drug selection and dosing.


Assuntos
Endocardite Bacteriana , beta-Lactamas , Animais , Humanos , beta-Lactamas/uso terapêutico , Antibacterianos/farmacologia , Endocardite Bacteriana/tratamento farmacológico , Monobactamas , Estado Terminal/terapia
14.
Gastroenterology ; 161(5): 1412-1422, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34270955

RESUMO

BACKGROUND AND AIMS: Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from "on PPI" pH impedance studies predicting need for escalation of therapy. METHODS: De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n = 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n = 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n = 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response. RESULTS: Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management. CONCLUSION: Combinations of abnormal "on PPI" pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.


Assuntos
Monitoramento de Medicamentos , Monitoramento do pH Esofágico , Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Esquema de Medicação , Impedância Elétrica , Europa (Continente) , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Azia/diagnóstico , Azia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
15.
Clin Gastroenterol Hepatol ; 20(3): e398-e406, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144149

RESUMO

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.


Assuntos
Acalasia Esofágica , Transtornos da Motilidade Esofágica , Adolescente , Adulto , Idoso , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/epidemiologia , Junção Esofagogástrica , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Adulto Jovem
16.
Expert Opin Emerg Drugs ; 27(1): 55-73, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35266839

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS) is a symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of diverse treatment strategies. This mechanistic heterogeneity suggests that available therapies will only prove effective in a subset of IBS sufferers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options. AREAS COVERED: Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function. EXPERT OPINION: While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.


Assuntos
Síndrome do Intestino Irritável , Constipação Intestinal/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/tratamento farmacológico
17.
J Clin Gastroenterol ; 56(10): 821-830, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084164

RESUMO

With the advent of high-resolution esophageal manometry, it is recognized that the antireflux barrier receives a contribution from both the lower esophageal sphincter (intrinsic sphincter) and the muscle of the crural diaphragm (extrinsic sphincter). Further, an increased intra-abdominal pressure is a major force responsible for an adaptive response of a competent sphincter or the disruption of the esophagogastric junction resulting in gastroesophageal reflux, especially in the presence of a hiatal hernia. This review describes how the pressure dynamics in the lower esophageal sphincter were discovered and measured over time and how this has influenced the development of antireflux surgery.


Assuntos
Refluxo Gastroesofágico , Hérnia Hiatal , Esfíncter Esofágico Inferior , Junção Esofagogástrica , Humanos , Manometria , Pressão
18.
Dig Dis Sci ; 67(6): 2347-2357, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34435269

RESUMO

BACKGROUND/AIMS: Inadequate bowel preparation leads to poor outcomes in colonoscopy. Prior investigations have demonstrated improved bowel preparation with pre-procedural educational videos. We aimed to determine whether an interactive, online educational video could improve bowel preparation scores in an outpatient population. METHODS: We performed a prospective, endoscopist-blinded, randomized controlled trial at our hospital-based outpatient endoscopy center. Eligible patients were randomized to two groups. Both groups received standard verbal and written instructions, while the intervention group also received access to an interactive, online video. The primary outcome was improvement in the bowel preparation scores graded using the Boston bowel prep score (BBPS). Secondary outcomes included adenoma detection rate, total number of polyps detected, patient satisfaction, pre-procedure anxiety, and complication rates. RESULTS: The difference in BBPS in the intervention group (8) compared to the control group (7.6) did not meet statistical significance in our primary outcome of improvement in BBPS (p = 0.076). However, on subgroup analysis, there was a statistically significant improvement in BBPS in the intervention group among African Americans (p = 0.007) and patients older than 65 (p = 0.026). Those in the intervention arm rated pre-procedural materials "very easy" to understand significantly more often than in the control arm (p = 0.018). CONCLUSIONS: Use of an interactive, online educational video for bowel preparation did not lead to improvement in overall BBPS. However, among patients at higher risk for inadequate bowel preparation, such as African Americans and elderly patients, there may be a benefit.


Assuntos
Adenoma , Treinamento por Simulação , Adenoma/diagnóstico , Idoso , Catárticos , Colonoscopia/métodos , Humanos , Estudos Prospectivos , Projetos de Pesquisa
19.
Intern Med J ; 52(12): 2172-2175, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36436197

RESUMO

Coronavirus disease 2019 (COVID-19) infection in patients with haematological neoplasms has been associated with increased mortality; however, many studies in this patient group were reported early in the pandemic. The authors evaluated outcomes of COVID-19 infection in patients with haematological conditions following widespread vaccination, newer viral variants and increasingly effective antiviral therapies. A 4% mortality rate was found and contemporary risk factors for hospitalisation including older age, nonvaccination or partial COVID-19 vaccination status and infection with non-Omicron strain were identified.


Assuntos
COVID-19 , Neoplasias Hematológicas , Hematologia , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Neoplasias Hematológicas/terapia
20.
Intern Med J ; 52(2): 214-222, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34490712

RESUMO

BACKGROUND: The COVID-19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence-based therapies to combat disease. In particular, the use of off-label therapies outside of a clinical trial setting has been controversial. AIM: To longitudinally study policies and prescribing practices pertaining to therapies for COVID-19 in Australian health services during 2020. METHODS: Prospective data were collected from participating Australian health services who may care for patients with COVID-19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID-19 policy at their service and use of therapies for COVID-19. RESULTS: Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39; 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID-19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID-19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. CONCLUSION: Our results reflect the reactive nature of prescribing of therapies for COVID-19 and highlight the importance of evidence-based guidelines to assist prescribers.


Assuntos
COVID-19 , Austrália/epidemiologia , Serviços de Saúde , Humanos , Pandemias , Políticas , Estudos Prospectivos , SARS-CoV-2 , Inquéritos e Questionários
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