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1.
Sex Transm Infect ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937097

RESUMEN

BACKGROUND: A number of females with pelvic inflammatory disease will present to general surgical services with non-specific abdominal pain. Screening for sexually transmitted infections (STI) as an underlying cause is not routinely offered. We therefore established an STI screening programme for young females presenting to a same day emergency ambulatory surgical clinic as part of the diagnostic pathway. Data outlining the incidence and prevalence of STIs as the underlying cause of lower abdominal pain were collected. METHODS: We conducted an observational cohort study. Self-collected vulvovaginal swabs for chlamydia and gonorrhoea were offered as part of a standardised diagnostic pathway for all females meeting inclusion criteria presenting with abdominal pain. Positive results were referred to our local sexual health team for treatment and contact tracing. RESULTS: The cohort comprised 297 eligible patients; 259 participated, 20 patients declined testing and 18 samples were rejected as inadequate in the laboratory. 5.4% of swab results were positive (2 gonorrhoea and 12 chlamydia). All patients with positive swabs had presented with lower abdominal pain and of these only 21% had a documented sexual history. CONCLUSION: Undiagnosed STIs are prevalent, with significant fertility and public health risks. Young females seeking medical assessment for abdominal pain provide an opportunistic screening cohort with a likely subset of patients presenting with abdominal pain as a direct result of an STI. Our results demonstrate a high incidence of positive tests, suggesting further training of surgeons to include a sexual history in assessment of females with abdominal pain is vital.

2.
Nurs Adm Q ; 48(3): 248-252, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38848487

RESUMEN

Patient falls within the hospital setting continue to be a significant challenge globally with almost one million hospital falls occurring in the U.S. annually. Recent calculations showed that the average total cost of a hospitalized patient fall was $62,521. One evidenced-based tool that has been shown to be effective is a colorful laminated poster, Fall TIPS poster, that was designed to engage and involve the patient in their fall prevention. One academic medical center utilized this implementation showing a successful return on investment (ROI). This project used a pre-post implementation design. After a successful pilot using the poster on one unit, the implementation was spread to all Adult Acute Care units (n = 10) within the institution. The outcome measures were fall and fall with injury counts and rates. The process measure was the completion of the fall prevention poster measured via audits. The calculation of ROI was completed using a four-step framework. The outcome data of fall and fall with injury showed a decrease from the pre-intervention months with both the fall count and rate decreasing by 23% and the fall with injury count and rate decreasing by 40%. The overall ROI calculation estimated an ROI of $982,700. The successful results from this project support the evidence that shows this program and the use of the Fall TIPS poster helps reduce patient falls within the hospital and yields a favorable ROI.


Asunto(s)
Accidentes por Caídas , Accidentes por Caídas/prevención & control , Accidentes por Caídas/economía , Humanos , Proyectos Piloto , Administración de la Seguridad/métodos , Administración de la Seguridad/economía , Administración de la Seguridad/normas
3.
Cancer ; 129(7): 1041-1050, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36718624

RESUMEN

BACKGROUND: Senaparib is a novel, selective poly(ADP-ribose) polymerase-1/2 inhibitor with strong antitumor activity in preclinical studies. This first-in-human, phase 1, dose-escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors. METHODS: Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose-escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose-limiting toxicity occurred within 7 days, they received senaparib once daily in 3-week cycles. The primary end points were safety and tolerability. RESULTS: Thirty-nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose-limiting toxicities were observed in any cohort. Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06-1.67, and absorption saturation was 80-150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation-positive subgroup and 6.3% for the nonmutated subgroup. CONCLUSIONS: Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily. GOV ID: NCT03507543.


Asunto(s)
Antineoplásicos , Neoplasias , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Australia , Dosis Máxima Tolerada , Neoplasias/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico
4.
Br J Surg ; 110(11): 1535-1542, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37611141

RESUMEN

BACKGROUND: Surgical errors are acts or omissions resulting in negative consequences and/or increased operating time. This study describes surgeon-reported errors in laparoscopic cholecystectomy. METHODS: Intraoperative videos were uploaded and annotated on Touch SurgeryTM Enterprise. Participants evaluated videos for severity using a 10-point intraoperative cholecystitis grading score, and errors using Observational Clinical Human Reliability Assessment, which includes skill, consequence, and mechanism classifications. RESULTS: Nine videos were assessed by 8 participants (3 junior (specialist trainee (ST) 3-5), 2 senior trainees (ST6-8), and 3 consultants). Participants identified 550 errors. Positive relationships were seen between total operating time and error count (r2 = 0.284, P < 0.001), intraoperative grade score and error count (r2 = 0.578, P = 0.001), and intraoperative grade score and total operating time (r2 = 0.157, P < 0.001). Error counts differed significantly across intraoperative phases (H(6) = 47.06, P < 0.001), most frequently at dissection of the hepatocystic triangle (total 282; median 33.5 (i.q.r. 23.5-47.8, range 15-63)), ligation/division of cystic structures (total 124; median 13.5 (i.q.r. 12-19.3, range 10-26)), and gallbladder dissection (total 117; median 14.5 (i.q.r. 10.3-18.8, range 6-26)). There were no significant differences in error counts between juniors, seniors, and consultants (H(2) = 0.03, P = 0.987). Errors were classified differently. For dissection of the hepatocystic triangle, thermal injuries (50 in total) were frequently classified as executional, consequential errors; trainees classified thermal injuries as step done with excessive force, speed, depth, distance, time or rotation (29 out of 50), whereas consultants classified them as incorrect orientation (6 out of 50). For ligation/division of cystic structures, inappropriate clipping (60 errors in total), procedural errors were reported by junior trainees (6 out of 60), but not consultants. For gallbladder dissection, inappropriate dissection (20 errors in total) was reported in incorrect planes by consultants and seniors (6 out of 20), but not by juniors. Poor economy of movement (11 errors in total) was reported more by consultants (8 out of 11) than trainees (3 out of 11). CONCLUSION: This study suggests that surgical experience influences error interpretation, but the benefits for surgical training are currently unclear.


Asunto(s)
Colecistectomía Laparoscópica , Humanos , Colecistectomía Laparoscópica/métodos , Disección , Vesícula Biliar , Ligadura , Reproducibilidad de los Resultados
5.
Cancer Immunol Immunother ; 71(10): 2371-2379, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35165764

RESUMEN

BACKGROUND: The safety and anti-tumor activity of penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study. METHODS: Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of penpulimab. In the Phase Ia/Ib trial in Australia, patients received penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of penpulimab in patients with UGI cancers in these two trials were evaluated. RESULTS: A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received penpulimab with a median of 6 (1-64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date. CONCLUSIONS: Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted. TRIAL REGISTRATION: Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506).


Asunto(s)
Anticuerpos Monoclonales , Neoplasias Gastrointestinales , Inhibidores de Puntos de Control Inmunológico , Anticuerpos Monoclonales/efectos adversos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoglobulina G
6.
Molecules ; 26(23)2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-34885848

RESUMEN

Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function.


Asunto(s)
Fosfolipasas A2 Grupo II/metabolismo , Desarrollo de Medicamentos , Fosfolipasas A2 Grupo II/antagonistas & inhibidores , Fosfolipasas A2 Grupo II/farmacología , Humanos , Neoplasias/diagnóstico , Neoplasias/enzimología , Pronóstico
7.
Cancer Immunol Immunother ; 68(12): 1921-1934, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31637475

RESUMEN

Blockade of the PD-1/PD-L1 pathway with targeted monoclonal antibodies has demonstrated encouraging anti-tumour activity in multiple cancer types. We present the case of a patient with BRAF-negative stage IVC anaplastic thyroid cancer (ATC) treated with the anti-PD-1 monoclonal antibody, pembrolizumab, following radiographic progression on chemoradiation. Blood samples were collected prior to and at four time points during treatment with pembrolizumab. Mass cytometry was used to determine expression of relevant biomarkers by peripheral blood mononuclear cells. Faecal samples were collected at baseline and 4 weeks following treatment initiation; taxonomic profiling using 16S ribosomal RNA (rRNA) gene sequencing was performed. Following treatment, a marked expansion in CD20+ B cell, CD16+ CD56lo NK cell and CD45RO+ CCR7+ central memory CD4+ T-cell populations was observed in the peripheral blood. Proportions of cells expressing the co-receptors TIGIT, OX40 and CD86 also increased during treatment. A high abundance of bacteria of the order Bacteroidales, specifically from the Bacteroidaceae and Rikenellaceae families, was identified in the faecal microbiota. Moreover, the patient's microbiome was enriched in Clostridiales order members Ruminococcaceae, Veillonellaceae and Lachnospiraceae. Alpha diversity of the gut microbiome was significantly higher following initiation of checkpoint therapy as assessed by the Shannon and Simpson index. Our results suggest that treatment with pembrolizumab promotes expansion of T-, B- and NK cell populations in the peripheral blood at the time of tumour regression and have the potential to be implemented as predictive biomarkers in the context of checkpoint blockade therapy. Larger studies to confirm these findings are warranted.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Heces/microbiología , Células Asesinas Naturales/inmunología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Bacteroides , Humanos , Masculino , Microbiota , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , ARN Ribosómico 16S/análisis
9.
J Sleep Res ; 28(3): e12637, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-29171171

RESUMEN

Sleep restriction degrades cognitive and motor performance, which can adversely impact job performance and increase the risk of accidents. Military personnel are prone to operating under sleep restriction, and previous work suggests that military marksmanship may be negatively affected under such conditions. Results of these studies, however, are mixed and have often incorporated additional stressors (e.g. energy restriction) beyond sleep restriction. Moreover, few studies have investigated how the degree of difficulty of a marksmanship task impacts performance following sleep restriction. The purpose of the current experiment was to study the effects of sleep restriction on marksmanship while minimizing the potential influence of other forms of stress. A friend-foe discrimination challenge with greater or lesser degrees of complexity (high versus low load) was used as the primary marksmanship task. Active duty Soldiers were recruited, and allowed 2 h of sleep every 24 h over a 72-h testing period. Marksmanship tasks, cognitive assessment metrics and the NASA-Task Load Index were administered daily. Results indicated that reaction times to shoot foe targets and signal friendly targets slowed over time. In addition, the ability to correctly discriminate between friend and foe targets significantly decreased in the high-cognitive-load condition over time despite shot accuracy remaining stable. The NASA-Task Load Index revealed that, although marksmanship performance degraded, participants believed their performance did not change over time. These results further characterize the consequences of sleep restriction on marksmanship performance and the perception of performance, and reinforce the importance of adequate sleep among service members when feasible.


Asunto(s)
Cognición/fisiología , Tiempo de Reacción/fisiología , Privación de Sueño/psicología , Análisis y Desempeño de Tareas , Adulto , Toma de Decisiones , Humanos , Masculino , Personal Militar
10.
Gut ; 67(3): 562-573, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-27902444

RESUMEN

OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein-Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. CONCLUSIONS: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.


Asunto(s)
Carcinoma Hepatocelular/terapia , Hepacivirus/fisiología , Neoplasias Hepáticas/terapia , Viroterapia Oncolítica , Virus Oncolíticos/inmunología , Reoviridae/inmunología , Animales , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/terapia , Linfoma de Burkitt/virología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Medios de Cultivo Condicionados/farmacología , Hepacivirus/inmunología , Hepatocitos , Herpesvirus Humano 4 , Humanos , Inmunidad Innata , Interferón-alfa/metabolismo , Interferón beta/metabolismo , Interferones , Interleucinas/metabolismo , Leucocitos Mononucleares , Hígado/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/virología , Ratones , Ratones SCID , Células T Asesinas Naturales/inmunología , Replicación Viral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Invest New Drugs ; 36(5): 886-894, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29766337

RESUMEN

Background The MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF) also known as scatter factor, are associated with tumourigenesis and metastasis by promotion of scattering, proliferation, angiogenesis, motility and invasion. ASLAN-002 is a potent inhibitor of MET as well as related kinases. A phase I dose escalation study was conducted to determine the safety and pharmacokinetics of ASLAN-002 in patients with advanced cancer. Methods Patients with advanced or metastatic solid tumours, who had progressed on standard therapy or for whom standard therapy was not known, were administered ASLAN-002 orally. The starting dose was 100 mg once daily (QD) with subsequent cohorts to receive doses of 200 mg QD, 300 mg QD, 450 mg QD, 600 mg QD, 300 mg twice daily (BID), 450 mg BID, and 600 mg BID. Results Forty patients were included across 7 dose cohorts. Cohort 8 (600 mg BID) was not opened due to the lack of appreciable pharmacokinetic (PK) differences between 300 mg BID and 450 mg BID and higher incidences of grade 3 or 4 adverse events (AE) in Cohort 7 (450 mg BID). Fifteen patients (37.5%) experienced a grade 3 or 4 AE. The most commonly reported AEs were nausea (55%), fatigue (47.5%) and constipation (30%). One dose limiting toxicity (DLT) of atrial fibrillation was observed with 450 mg BID. Conclusions ASLAN-002 is well tolerated at 300 mg BID and is the recommended dose for future phase II studies (RP2D). Clinical Trials Registry Number: NCT01721148 .


Asunto(s)
Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/metabolismo , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Fatiga/inducido químicamente , Fatiga/metabolismo , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/metabolismo , Neoplasias/metabolismo
12.
Chemistry ; 24(68): 17986-17996, 2018 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-30222223

RESUMEN

The modular structure of metal-organic framework nanosheets (MONs) provides a convenient route to creating two-dimensional materials with readily tuneable surface properties. Here, the liquid exfoliation of two closely related layered metal-organic frameworks functionalised with either methoxy-propyl (1) or pentyl (2) pendent groups intended to bestow either hydrophilic or hydrophobic character to the resulting nanosheets is reported. Exfoliation of the two materials in a range of different solvents highlighted significant differences in their dispersion properties, as well as their molecular and nanoscopic structures. Exchange or loss of solvent was found to occur at the labile axial position of the paddle-wheel based MONs and DFT calculations indicated that intramolecular coordination by the oxygen of the methoxy-propyl pendant groups may take place. The nanoscopic dimensions of the MONs were further tuned by varying the exfoliation conditions and through "liquid cascade centrifugation". Aqueous suspensions of the nanosheets were used as sensors to detect aromatic heterocycles with clear differences in binding behaviour observed and quantified.

14.
BMC Psychiatry ; 18(1): 48, 2018 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-29452590

RESUMEN

BACKGROUND: Posttraumatic stress disorder (PTSD) can have long-term and far-reaching impacts on health and social and occupational functioning. This study examined factors associated with persistent PTSD among U.S. service members and veterans. METHODS: Using baseline and follow-up (2001-2013) questionnaire data collected approximately every 3 years from the Millennium Cohort Study, multivariable logistic regression was conducted to determine factors associated with persistent PTSD. Participants included those who screened positive for PTSD using the PTSD Checklist-Civilian Version at baseline (N = 2409). Participants were classified as having remitted or persistent PTSD based on screening negative or positive, respectively, at follow-up. RESULTS: Almost half of participants (N = 1132; 47%) met criteria for persistent PTSD at the first follow-up; of those, 804 (71%) also screened positive for PTSD at the second follow-up. Multiple factors were independently associated with persistent PTSD in an adjusted model at the first follow-up, including older age, deployment with high combat exposure, enlisted rank, initial PTSD severity, depression, history of physical assault, disabling injury/illness, and somatic symptoms. Among those with persistent PTSD at the first follow-up, additional factors of less sleep, separation from the military, and lack of social support were associated with persistent PTSD at the second follow-up. CONCLUSIONS: Combat experiences and PTSD severity were the most salient risk factors for persistent PTSD. Comorbid conditions, including injury/illness, somatic symptoms, and sleep problems, also played a significant role and should be addressed during treatment. The high percentage of participants with persistent PTSD supports the need for more comprehensive and accessible treatment, especially after separation from the military.


Asunto(s)
Campaña Afgana 2001- , Guerra de Irak 2003-2011 , Personal Militar/psicología , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicología , Veteranos/psicología , Adulto , Estudios de Cohortes , Trastornos de Combate/diagnóstico , Trastornos de Combate/epidemiología , Trastornos de Combate/psicología , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Estudios Prospectivos , Factores de Riesgo , Trastornos por Estrés Postraumático/epidemiología , Encuestas y Cuestionarios , Estados Unidos , Veteranos/estadística & datos numéricos
15.
J Gastroenterol Hepatol ; 30(4): 657-66, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25641691

RESUMEN

Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1 mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Colitis/inducido químicamente , Inmunosupresores/administración & dosificación , Melanoma/tratamiento farmacológico , Melanoma/secundario , Anticuerpos Monoclonales/uso terapéutico , Azatioprina/administración & dosificación , Inhibidores de la Calcineurina/administración & dosificación , Colitis/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Humanos , Infliximab/administración & dosificación , Ipilimumab , Metilprednisolona/administración & dosificación , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Grupo de Atención al Paciente , Prednisolona/administración & dosificación , Quimioterapia por Pulso
16.
Anticancer Res ; 44(5): 2095-2102, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677731

RESUMEN

BACKGROUND/AIM: Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT. PATIENTS AND METHODS: We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index. RESULTS: A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals. CONCLUSION: Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.


Asunto(s)
Neoplasias , Humanos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Australia/epidemiología , Adulto , Anciano de 80 o más Años , Ensayos Clínicos como Asunto
17.
Am J Infect Control ; 51(6): 710-713, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36002082

RESUMEN

The University of California, San Francisco (UCSF) Hospital Epidemiology and Infection Prevention and the Department of Nursing used lessons-learned during COVID-19 as a foundation to create a framework to be used as a guide for converting an inpatient unit to a pandemic-response unit. This article provides details of this framework and other lessons learned that can be applied to other pandemic pathogens.


Asunto(s)
COVID-19 , Humanos , Pandemias/prevención & control , Pacientes Internos , San Francisco/epidemiología
18.
JBI Evid Implement ; 21(4): 310-324, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37036334

RESUMEN

INTRODUCTION AND OBJECTIVE: Advance care planning (ACP) communication and documentation are often inadequate, leading to care that is inconsistent with patients' preferences and moral dilemmas for family members. Nurses are patient advocates optimally positioned to initiate ACP but many feel that they lack the training and skills to navigate these conversations. The objective of this project was to increase nurses' capacity to engage in ACP. METHODS: This project used the JBI audit and feedback method to implement evidence into practice. The JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit tools were used to incorporate ACP into nursing workflow. Eight audit criteria were created based on a JBI evidence summary. Compliance was measured by reviewing ACP notes from electronic health records and online survey responses. A baseline audit was followed by educational presentations and development of posted materials. Three follow-up audits examined sustainability. RESULTS: Compliance with the best practice recommendation for nurses to engage in ACP discussions increased from 55% to 80%. There was improvement from zero ACP notes at baseline (0% compliance) to 12 ACP notes in the final audit. Of these notes, 42% included all best practice elements and 92% included patients' treatment preferences. CONCLUSIONS: Development of an integrative nursing education plan for ACP empowers nurses to engage in vital conversations. Informing nurses of their scope of practice, defining terms and expectations, and encouraging them to attempt and document conversations will benefit patients. Future initiatives would benefit from incorporating practical opportunities without real-life implications and providing continued support to cohorts.


Asunto(s)
Planificación Anticipada de Atención , Cuidado de Transición , Humanos , Comunicación , Poder Psicológico
19.
JBI Evid Implement ; 21(4): 386-393, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37957810

RESUMEN

ABSTRACT: There are many theories, models, and frameworks that have been proposed in the field of implementation science. Despite this, many evidence implementation or practice improvement projects do not consider these theories, models, or frameworks in their improvement efforts. The JBI approach is one example of an implementation theory, model, or framework. This approach has been developed particularly with health care professionals in mind and is designed to clearly guide pragmatic evidence implementation efforts based on the best available evidence. In this paper, we discuss how the JBI approach to evidence implementation can interact with and support theory-informed, pragmatic evidence implementation projects.


Asunto(s)
Personal de Salud , Ciencia de la Implementación , Humanos
20.
J Surg Educ ; 80(7): 994-1004, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37164903

RESUMEN

OBJECTIVE: This study compares the intraoperative phase times in laparoscopic cholecystectomy performed by an attending surgeon and supervised residents over 10-years to assess operative times as a marker of performance and any impact of case severity on times. DESIGN: Laparoscopic cholecystectomy videos were uploaded to Touch Surgery™ Enterprise, a combined software and hardware solution for securely recording, storing, and analysing surgical videos, which provide analytics of intraoperative phase times. Case severity and visualisation of the critical view of safety (CVS) were manually assessed using modified 10-point intraoperative gallbladder scoring system (mG10) and CVS scores, respectively. Attending and residents' times were compared unmatched and matched by mG10. SETTING: Secondary analysis of anonymized laparoscopic cholecystectomy video, recorded as standard of care. PARTICIPANTS: Adult patients who underwent elective laparoscopic cholecystectomy a single UK hospital. Cases were performed by one attending and their residents. RESULTS: 159 (attending=96, resident=63) laparoscopic cholecystectomy videos and intraoperative phase times were reviewed on Touch Surgery™ Enterprise and analyzed. Attending cases were more challenging (p=0.037). Residents achieved higher CVS scores (p=0.034) and showed longer dissection of hepatocystic triangle (HCT) times (p=0.012) in more challenging cases. Residents' total operative time (p=0.001) and dissection of HCT (p=0.002) times exceeded the attending's in low-severity matched cases (mG10=1). Residents' total operative times (p<0.001), port insertion/gallbladder exposure (p=0.032), and dissection of HCT (p<0.001) exceeded the attending's in matched cases (mG10=2). Residents' total operative (p<0.001), dissection of HCT (p<0.001), and gallbladder dissection (p=0.010) times exceeded the attendings in unmatched cases. CONCLUSIONS: Residents' total operative and dissection of HCT times significantly exceeded the attending's unmatched cases and low-severity matched cases which could suggest training need, however, also reflects an expected assessment of competence, and validates time as a marker of performance.


Asunto(s)
Colecistectomía Laparoscópica , Internado y Residencia , Cirujanos , Adulto , Humanos , Colecistectomía Laparoscópica/educación , Disección
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