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BACKGROUND: Little is known about the aetiologies and relevant allergens in paediatric patients with hand eczema (HE). OBJECTIVES: To characterize the aetiologies and determine the proportion of positive and currently relevant allergens in children/adolescents (age < 18 years) with HE referred for patch testing. METHODS: A retrospective analysis (2000-2016) of North American Contact Dermatitis Group data was performed. RESULTS: Of 1634 paediatric patients, 237 (14·5%) had involvement of the hands. Final physician diagnoses included allergic contact dermatitis (49·4%), atopic dermatitis (37·1%) and irritant contact dermatitis (16·9%). In multivariable logistic regression models, employment was the only association with increased odds of any HE or primary HE. Children with HE vs. those without HE had similar proportions of positive patch tests (56·1% vs. 61·7%; χ2 -test, P = 0·11). The five most common currently relevant allergens were nickel, methylisothiazolinone, propylene glycol, decyl glucoside and lanolin. In multivariable logistic regression models of the top 20 relevant allergens, HE was associated with significantly higher odds of currently relevant reactions to lanolin, quaternium-15, Compositae mix, thiuram mix, 2-mercaptobenzathiazole and colophony. The allergens with the highest mean significance-prevalence index number were methylisothiazolinone, carba mix, thiuram mix, nickel and methylchloroisothiazolinone/methylisothiazolinone. CONCLUSIONS: Children with HE who were referred for patch testing had a high proportion of positive patch tests, which was similar to the proportion found in children without HE. Children with HE had a distinct and fairly narrow profile of currently relevant allergens.
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Dermatite Alérgica de Contato , Eczema , Adolescente , Alérgenos/efeitos adversos , Criança , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Eczema/induzido quimicamente , Eczema/diagnóstico , Eczema/epidemiologia , Humanos , América do Norte/epidemiologia , Testes do Emplastro , Estudos RetrospectivosRESUMO
Laser vaporization of uranium in a pulsed supersonic expansion of nitrogen is used to produce complexes of the form U+(N2)n (n = 1-8). These ions are mass selected in a reflectron time-of-flight spectrometer and studied with visible and UV laser fixed-frequency photodissociation and with tunable infrared laser photodissociation spectroscopy. The dissociation patterns and spectroscopy of U+(N2)n indicate that N2 ligands are intact molecules and that there is no insertion chemistry resulting in UN+ or NUN+. Fixed frequency photodissociation at 532 and 355 nm indicate that the U+-N2 bond dissociation energy varies little with changing coordination. The photon energy and the number of ligands eliminated allow an estimate of the average U+-N2 dissociation energy of 12 kcal/mol. Infrared bands are observed for these complexes near the N-N stretch vibration via elimination of N2 molecules. These resonances are observed to be shifted about 130 cm-1 to the red from the free-N2 frequency for complexes with n = 3-8. Density functional theory indicates that U+ is most stable in the sextet state in these complexes and that N2 molecules bind in end-on configurations. The fully coordinated complex is predicted to be U+(N2)8, which has a cubic structure. The vibrational frequencies predicted by theory are consistently lower than those in the experiment, independent of the isomeric structure or spin state of the complexes. Despite its failure to reproduce the infrared spectra, theory provides an average U+-N2 dissociation energy of 11.8 ± 0.5 kcal/mol, in good agreement with the value from the experiments.
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BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement is one of the most common methods for establishing durable enteral access. Early PEG dislodgement occurs in < 5% of cases but typically prompts urgent surgical intervention to reestablish the gastrocutaneous tract and prevent intra-abdominal sepsis. To date, there is a single case report in the literature where successful endoscopic "rescue" of an early dislodged PEG tube negated the need for operative intervention. Here, we report our experience with a series of endoscopic PEG rescues for early dislodged PEG tubes. METHODS: A retrospective analysis of cases was reviewed from two institutions. Patients with early PEG dislodgements underwent PEG rescue using a gastroscope and standard Ponsky "Pull" PEG techniques through the original tract. RESULTS: Eleven patients were identified from the database and underwent PEG rescue after early PEG dislodgement. Mean operative time was 68 min, and there were no complications related to PEG rescue. PEG rescue permitted safe re-establishment of the gastrostomy tract while avoiding laparoscopic or open surgical intervention in hemodynamically stable patients. All patients tolerated the procedure well and were able to resume use of the PEG tubes shortly after intervention. CONCLUSION: Endoscopic rescue represents a feasible noninvasive option for PEG tube replacement following early inadvertent PEG tube dislodgement in appropriate clinical settings.
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Endoscopia , Gastrostomia , Intubação Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia , Estudos Retrospectivos , Estomas CirúrgicosRESUMO
PURPOSE: Evidence suggests that the distinctive relational qualities of peer support-compared to clinical-patient relationships-can be eroded in regulated healthcare environments. Measurement of fidelity in trials of peer support is lacking. This paper reports the development and testing of a fidelity index for one-to-one peer support in mental health services, designed to assess fidelity to principles that characterise the distinctiveness of peer support. METHODS: A draft index was developed using expert panels of service user researchers and people doing peer support, informed by an evidence-based, peer support principles framework. Two rounds of testing took place in 24 mental health services providing peer support in a range of settings. Fidelity was assessed through interviews with peer workers, their supervisors and people receiving peer support. Responses were tested for spread and internal consistency, independently double rated for inter-rater reliability, with feedback from interviewees and service user researchers used to refine the index. RESULTS: A fidelity index for one-to-one peer support in mental health services was produced with good psychometric properties. Fidelity is assessed in four principle-based domains; building trusting relationships based on shared lived experience; reciprocity and mutuality; leadership, choice and control; building strengths and making connections to community. CONCLUSIONS: The index offers potential to improve the evidence base for peer support in mental health services, enabling future trials to assess fidelity of interventions to peer support principles, and service providers a means of ensuring that peer support retains its distinctive qualities as it is introduced into mental health services.
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Transtornos Mentais , Serviços de Saúde Mental , Aconselhamento , Humanos , Transtornos Mentais/terapia , Grupo Associado , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The technical difficulty and steep learning curve of transanal total mesorectal excision (taTME) has limited widespread adoption. The single-port (SP) daVinci robot is designed to facilitate single-incision and natural-orifice transluminal endoscopic surgery (NOTES). This paper describes the first clinical experience of single-port robotic taTME (SP rTaTME). METHODS: This was a prospective study on consecutive patients with rectal cancer who underwent SP rTaTME proctosigmoidectomy with handsewn coloanal anastomosis in December 2018 and January 2019. The primary outcome was technical feasibility of the procedure. The secondary outcomes include blood loss, intraoperative complications, length of hospital stay, quality of the TME specimen, short- and long-term morbidity and mortality, as well as short-term oncologic follow -up. RESULTS: There were two patients, a 48-year-old male and a 38-year-old female. Both operations were completed successfully without complications or conversion. Estimated blood loss was 200 mL and 130 mL. In both cases the TME was completed transanally using the SP robot. In the first patient, the abdominal portion was completed through an abdominal single-incision; in the second patient the operation was entirely performed transanally as a pure NOTES procedure. In both cases, the final pathology report showed a complete TME with negative margins. Patients were discharged on postoperative day 3 and 4,respectively. There was no long-term morbidity or mortality. CONCLUSIONS: SP rTaTME is feasible and can be safely performed. It provides excellent optics and dexterity to work in a limited space. Future studies are required to further define the safety profile and the ultimate utility of the SP robot for taTME.
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Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Endoscópica Transanal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Neoplasias Retais/cirurgia , Reto/cirurgiaRESUMO
BACKGROUND: The new da Vinci Single-Port (SP) robot is a single-arm four-channel robotic system well suited for endoluminal surgery. We report our initial experience performing SP robotic transanal minimally invasive surgery (SP rTAMIS) for rectal neoplasms. METHODS: Under Institutional Review Board approval, two patients with rectal neoplasms were prospectively enrolled for elective SP rTAMIS. The primary endpoint was to report the safety and feasibility of successful procedure completion with the SP robot. Secondary endpoints included patient characteristics and perioperative metrics. RESULTS: Both patients underwent successful SP rTAMIS resection of rectal neoplasms without intraoperative complications or conversions. The lesions were 4.0 cm and 3.0 cm in size, located 6 cm and 7 cm cephalad to the anorectal ring. Excisions were full thickness with no piecemeal extractions or specimen fragmentation. Estimated blood loss was 0 mL and 30 mL. The mean excised area was 13.4 cm2 (22.7 cm2 and 9.0 cm2). The mean docking time was 5.25 min (range 2-8 min) and mean console time was 122.5 min (98 min and 147 min). Patients tolerated a liquid diet on postoperative day (POD) 0 and were discharged on POD 1 after tolerating a low residue diet and having bowel function. Pathology showed two adenomas with negative margins. There was no immediate or delayed morbidity or mortality. CONCLUSIONS: Our initial experience indicates that SP rTAMIS is a safe and feasible approach for local excision of rectal lesions. While SP rTAMIS is very promising, more experience with this approach is necessary to determine its widespread applicability.
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Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgia Endoscópica Transanal , Canal Anal/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Retais/cirurgia , RetoRESUMO
The vibrational spectra of H3 +Ar2,3 and D3 +Ar2,3 are investigated in the 2000 cm-1 to 4500 cm-1 region through a combination of mass-selected infrared laser photodissociation spectroscopy and computational work including the effects of anharmonicity. In the reduced symmetry of the di-argon complex, vibrational activity is detected in the regions of both the symmetric and antisymmetric hydrogen stretching modes of H3 +. The tri-argon complex restores the D3h symmetry of the H3 + ion, with a concomitant reduction in the vibrational activity that is limited to the region of the antisymmetric stretch. Throughout these spectra, additional bands are detected beyond those predicted with harmonic vibrational theory. Anharmonic theory is able to reproduce some of the additional bands, with varying degrees of success.
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BACKGROUND: The da Vinci Single-Port (SP) robot is a novel platform designed to facilitate single-incision robotic surgery (rSILS). The objective of this study was to describe our initial experience using this platform for SP robotic (SPr) right colectomy. METHODS: Under a Food and Drug Administration-regulated feasibility study and Institutional Review Board approval, a patient with cecal adenocarcinoma underwent an SPr right colectomy. The primary endpoint was the safety and feasibility of the first SPr right colectomy performed in the USA. Secondary endpoints included perioperative metrics, morbidity and mortality. RESULTS: An SPr Standard right colectomy was performed through a 4-cm single incision without the need for conversion or additional port placement. Estimated blood loss was 100 mL and there were no intraoperative complications. The robot was docked once with a docking time of 19 min. Total console time was 116 min and operative time was 219 min. The patient tolerated clear liquids on postoperative day (POD) 0 and a low-residue diet on POD 1. The patient had flatus and a bowel movement on POD 1. She was discharged home on POD 3. Final pathology showed pT3N0 cecal adenocarcinoma with negative margins and 0/24 lymph nodes positive for disease. CONCLUSIONS: Our initial experience demonstrates that an SPr right colectomy is feasible and can be safely completed. We completed an oncologic resection of a cecal adenocarcinoma without complications. The SP robot facilitates the utilization of robotic technology in a single-incision platform to perform colorectal procedures and offers promising benefits in the advancement of robotic surgery.
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Neoplasias do Ceco , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias do Ceco/cirurgia , Colectomia , Feminino , Humanos , Duração da CirurgiaRESUMO
BACKGROUND: The single-port daVinci robot is a new platform designed to facilitate single-incision surgeries. The objective of this study was to describe the first clinical experience in colorectal surgery using a novel single-port robotic system and report its feasibility and safety. METHODS: After Institutional Review Board approval was obtained and the study was registered with ClinicalTrials.gov, we performed single port robot-assisted left colectomy using the novel daVinci SP surgical system on two patients. The surgeries were completed through a single incision. The multichannel port accommodates a three-dimensional articulating camera and three double-jointed articulating instruments. The primary aim of this study was to report, for the first time in the USA, the technical feasibility of the procedure in the living human. The secondary aim was to report the outcomes including blood loss, number of incisions, number of dockings, docking time of the robot, incision length, operative time, console time, need for additional port and instrumentation, intraoperative complications, morbidity and mortality, time for tolerating diet, bowel function, and discharge. RESULTS: Both surgeries were completed without conversion through a single incision, 4.0 and 4.5 cm in size. Estimated blood loss was less than 60 ml in both cases. The robot was docked two and three times. Mean time to dock was 13 min (range 3-33 min). There were no intraoperative complications, no morbidity or death. Discharges occurred on postoperative days 2 and 3. CONCLUSIONS: Single-port robotic colectomy using the new robot is feasible and can be safely completed. The overall utility and functionality of the SP robot portends wide utilization and expansion of this technique. Careful development and analysis of the procedure outcomes, training, and cost will be necessary to properly advance the field.
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Colectomia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Duração da CirurgiaRESUMO
Manganese oxide cluster cations are produced by laser vaporization in a pulsed nozzle source and detected with time-of-flight mass spectrometry. The mass spectrum contains intense peaks for stoichiometries corresponding to (MnO) n+. Multiphoton photodissociation of these clusters yields smaller ions with the same stoichiometric ratio, either by sequential elimination of MnO units or by various fission processes with roughly equal efficiencies. Fragmentation of clusters containing excess oxygen also yields (MnO) n+ fragments. These apparently stable fragments are investigated further using density functional theory to determine their likely structures. The lowest energy structure for Mn2O2+ is found to be a planar ring, and those for Mn4O4+ and Mn6O6+ are cuboids. Mn3O3+ is predicted to have a six-membered ring structure and Mn5O5+ has a fused cube/ring configuration similar to the structure of the oxygen evolving center of Photosystem II. Open-shell, high-spin configurations on individual manganese atoms couple antiferromagnetically and ferromagnetically to produce low-spin and high-spin configurations on different sized clusters.
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AIM: Transanal transabdominal proctosigmoidectomy (TATA) with a coloanal anastomosis is an alternative to abdominoperineal excision of the rectum (APR) for low rectal cancer. Neorectal prolapse is an unusual complication following TATA. This study aimed to determine the incidence of neorectal prolapse after TATA for low rectal cancer. METHOD: This cohort study was conducted in a tertiary referral colorectal centre. From a prospectively maintained database including 1093 patients treated for rectal cancer between 1984 and 2016 we identified those who underwent sphincter-preserving surgery. Data regarding the incidence, management and outcomes of neorectal prolapse were analysed. RESULTS: A total of 409 patients were identified, of whom 185 underwent open surgery and 224 a minimally invasive surgical procedure (MIS). All received neoadjuvant chemoradiation. Neorectal prolapse occurred in 4.6% (n = 19) with an incidence of 2.2% in the open and 6.7% in the MIS group (P = 0.023), with no difference between MIS techniques. There was one recurrence of neorectal prolapse (5.9%). The incidence of neorectal prolapse was higher in women (9.5%) than men (2.5%) (P = 0.011). There were no differences in local recurrence rates between the neorectal prolapse group (5.3%) and our population without prolapse (3.4%) (P = 0.79). CONCLUSION: Neorectal prolapse is a rare occurrence following minimally invasive sphincter-saving surgical procedures performed for rectal cancer. It appears to be more frequent in patients who undergo MIS procedures and in women.
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Complicações Pós-Operatórias/epidemiologia , Proctocolectomia Restauradora/efeitos adversos , Neoplasias Retais/cirurgia , Prolapso Retal/epidemiologia , Cirurgia Endoscópica Transanal/efeitos adversos , Idoso , Canal Anal/cirurgia , Colo Sigmoide/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Proctocolectomia Restauradora/métodos , Estudos Prospectivos , Prolapso Retal/etiologia , Prolapso Retal/patologia , Cirurgia Endoscópica Transanal/métodosRESUMO
Approximately 10-15% of patients present with an advanced rectal cancer that extends beyond the conventional total mesorectal excision (TME) planes. In such cases extending the surgery to ensure resection with clear margins (R0 resection) is essential in order to achieve long-term cure. Professor Holm describes the techniques of beyond-TME exenterative surgery, the methods of patient selection and outcomes.
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Atitude do Pessoal de Saúde , Margens de Excisão , Protectomia/métodos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Consenso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Mesocolo/cirurgia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Exenteração Pélvica , Prognóstico , Neoplasias Retais/mortalidade , Medição de Risco , Cirurgiões/psicologia , Análise de SobrevidaRESUMO
From the patient's perspective, cancer cure with full preservation of function is a crucial goal. There are many advances that have emerged which may make this possible in a greater proportion of patients without compromising oncological outcomes. Professor Tekkis reviews the options and evidence to date for 'organ preservation' and the expert panel discuss the implications for current and future patient care.
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Quimiorradioterapia/métodos , Recidiva Local de Neoplasia/mortalidade , Tratamentos com Preservação do Órgão/métodos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Quimiorradioterapia/mortalidade , Consenso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Neoplasias Retais/mortalidade , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
In patients with advanced and recurrent colorectal cancer, surgical resection with clear margins is the greatest challenge and is limited by known anatomical constraints. Preoperative or intra-operative assessment of the limits of surgical dissection may help to explore the possibility of improving resectability through either targeted external beam radiotherapy or intra-operative radiotherapy. Professor Chang reviews the evidence base and potential advantages and disadvantages of this approach, whilst the expert panel agree a consensus on the evidence for assessment and therapy of such patients.
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Braquiterapia/métodos , Colectomia/métodos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/cirurgia , Cuidados Intraoperatórios/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Consenso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Cuidados Pré-Operatórios/métodos , Prognóstico , Dosagem Radioterapêutica , Medição de Risco , Análise de SobrevidaRESUMO
PURPOSE: Transanal surgery remains both an innovative approach to rectal pathology and a demonstrated technical challenge. Improved technology using a single-port system robotic platform (SPS) offers a promising option for this surgery. METHODS: SPS robotic system was utilized to perform submucosal, full-thickness and cylindrical excision on four cadavers. Operative performance and surgeon fatigue were measured. RESULTS: On all types of resections, the SPS system performed well. There were no piecemeal or fragmented resections. Closure was judged to be good to excellent in all cases. Surgeon assessment of setup and performance of the SPS was excellent in all cases. CONCLUSIONS: SPS robotic transanal surgery represents an exciting new option for transanal surgery.
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Reto/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação , Cirurgia Endoscópica Transanal/instrumentação , Adulto , Cadáver , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica Transanal/métodosRESUMO
Ion-molecule complexes of the form H+Arn are produced in pulsed-discharge supersonic expansions containing hydrogen and argon. These ions are analyzed and mass-selected in a reflectron spectrometer and studied with infrared laser photodissociation spectroscopy. Infrared spectra for the n = 3-7 complexes are characterized by a series of strong bands in the 900-2200 cm-1 region. Computational studies at the MP2/aug-cc-pVTZ level examine the structures, binding energies, and infrared spectra for these systems. The core ion responsible for the infrared bands is the proton-bound argon dimer, Ar-H+-Ar, which is progressively solvated by the excess argon. Anharmonic vibrational theory is able to reproduce the vibrational structure, identifying it as arising from the asymmetric proton stretch in combination with multiple quanta of the symmetric argon stretch. Successive addition of argon shifts the proton vibration to lower frequencies, as the charge is delocalized over more ligands. The Ar-H+-Ar core ion has a first solvation sphere of five argons.
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BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) has always made more sense in the colorectal field where the target organ for entry houses the pathology. To address the question whether an adequate total mesorectal excision (TME) for rectal cancer can be performed from a transanal bottoms-up approach, we performed a case-matched study. METHODS: Starting in 2009, transanal TME (taTME) surgery was selectively used for rectal cancer after neoadjuvant therapy and prospectively entered into a database. Between March 2012 and February 2014, 17 consecutive taTME rectal cancer patients were identified and case-matched to multiport laparoscopic TME (MP TME) based on age, body mass index, uT stage, radiation dose, level in the rectum, and procedure. Perioperative outcomes, morbidity, mortality, local recurrence, completeness of TME, and radial and distal margins were analyzed. Statistically significant differences were identified using Student's t test. RESULTS: There were 12 transanal abdominal transanal (TATA)/5 abdominoperineal resection procedures in each group. Data regarding overall/taTME/MP TME are as follows: % positive-circumferential margin: 2.9/0/5.9 % (p = 0.32). Distal margin: 0/0/0 %. Complete or near-complete TME: 97.1/100/94.1 % (p = 0.32). Incomplete TME 2.9/0/5.9 % (p = 0.32). Local recurrence: 2.9/5.9/0 % (p = 0.32). There were no perioperative mortalities. Morbidity in each group: 26.4/23.5/29.4 % (p = 0.79). There were no differences in perioperative or postoperative outcomes except days to clear liquids (1/2 days, p = 0.03) and largest incision length (1.3/2.6 cm, p = 0.05). CONCLUSIONS: We demonstrated no differences in perioperative/postoperative outcomes or pathologic TME outcomes of transanal or bottoms-up TME compared to standard laparoscopic TME. TaTME is a promising progressive approach to NOTES and deserves additional evaluation.
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Laparoscopia , Excisão de Linfonodo , Recidiva Local de Neoplasia , Neoplasias Retais/cirurgia , Cirurgia Endoscópica Transanal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimiorradioterapia Adjuvante , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Neoplasias Retais/terapia , Cirurgia Endoscópica Transanal/efeitos adversosRESUMO
To evaluate the efficacy and safety of anti-NGF antibody treatment in hip and knee osteoarthritis (OA), a systematic review and meta-analysis was undertaken utilizing the criteria described by the Cochrane collaboration. Both published and unpublished trials were identified for tanezumab, fulranumab and fasinumab in hip and knee OA; sponsors were contacted to provide and confirm data. Study quality was assessed by Jadad criteria; efficacy and safety data were extracted independently by two individuals and meta-analyses were performed using Revman 5.2. 13 randomized, controlled trials were identified: 10 of tanezumab, two of fulranumab and one with fasinumab. All agents demonstrated superiority in efficacy compared to placebo. The highest doses in the phase II studies of tanezumab had a standardized effect size for WOMAC pain of 0.73 (CI, 0.51, 0.95). Subsequent phase III studies of tanezumab and phase II studies of fulranumab and fasinumab reported standardized effect sizes for WOMAC pain of -0.15-0.5, with no clear distinction among dose levels. Tanezumab compared to NSAIDs and opioids showed greater efficacy with a standardized effect size for WOMAC pain of 0.23 (CI 0.17-0.29). WOMAC function and PGA results were similar to WOMAC pain. Safety, determined by odds ratios of withdrawals from studies due to adverse events (AEs), was better at the lower doses than higher doses and similar among all agents. These results demonstrate that antibodies to NGF provide efficacy in OA and that general safety at the lower doses appears similar to placebo. Additional data on both efficacy and safety of these antibodies are needed to define the optimal dose to maximize benefit to risk.
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Anticorpos Monoclonais/uso terapêutico , Fator de Crescimento Neural/antagonistas & inibidores , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Humanos , Resultado do TratamentoRESUMO
AIMS: To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT). METHODS: Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI). RESULTS: Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day. CONCLUSIONS: In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI.