RESUMEN
INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.
RESUMEN
INTRODUCTION: The fixed-ratio combination of insulin glargine (iGlar) plus lixisenatide (iGlarLixi) has proven efficacious in clinical trials; however, there is limited evidence of its benefits in a variety of real-world patients with type 2 diabetes mellitus (T2DM) who present in routine clinical practice. METHODS: A large integrated claims and EHR database was used to identify two real-world (RW) cohorts (ages ≥ 18) with T2DM who were eligible for treatment with iGlarLixi. At baseline, the first cohort (insulin cohort) received insulin with or without oral antidiabetic drugs (OADs), and the second cohort (OAD-only cohort) received OADs only. A Monte Carlo patient-level simulation was applied to each cohort based on treatment strategies and efficacies from the LixiLan-L and LixiLan-O trials to estimate reductions in glycated hemoglobin A1C (A1C) and the percentage achieving age-based A1C goals (≤ 7% for ages < 65 and ≤ 8% for ages ≥ 65) at 30 weeks. RESULTS: The RW insulin (N = 3797) and OAD-only (N = 17,633) cohorts differed considerably in demographics, age, clinical characteristics, baseline A1C levels, and background OAD therapies compared to the populations in the Lixilan-L and Lixilan-O trials. Regardless of the cohort description, A1C goals were achieved among 52.6% vs. 31.6% (p < 0.001) of patients in the iGlarLixi vs. the iGlar arms in the insulin cohort simulation, while A1C goals were achieved among 59.9% vs. 49.3% and 32.8% (p < 0.001) of patients in the OAD-only cohort simulation in the iGlarLixi vs. the iGlar and lixisenatide arms, respectively. CONCLUSIONS: Irrespective of the treatment regimen at baseline (insulin vs. OAD only), this patient-level simulation demonstrated that a greater proportion of patients achieved their A1C goals with iGlarlixi compared to iGlar or lixisenatide alone. These findings suggest that the benefits of iGlarLixi extend to clinically distinct RW populations.
RESUMEN
Gastric lipomas are rare benign tumours of the stomach, representing less than 3% of all benign gastric neoplasms. They are usually asymptomatic but larger lesions can present with abdominal pain, gastric outlet obstruction and haematemesis. Malignant transformation is extremely rare. Accurate preoperative diagnosis can be established with computed tomography. Being benign, extensive surgery is not necessary and simple excision of the lesion is adequate. Small asymptomatic lesions can be followed up. We present a case of 80-year-old woman with gastric submucosal lipoma who presented with haematemesis.
Asunto(s)
Hematemesis/etiología , Lipoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Anciano de 80 o más Años , Femenino , Humanos , Lipoma/complicaciones , Lipoma/cirugía , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugíaRESUMEN
The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.
Asunto(s)
Atmósfera/química , Ciclo del Carbono , Carbono/análisis , Geografía , Calentamiento Global , Suelo/química , Bases de Datos Factuales , Ecosistema , Retroalimentación , Modelos Estadísticos , Reproducibilidad de los Resultados , TemperaturaRESUMEN
BACKGROUND: Surveillance of antimicrobial resistance (AMR) is of great importance. Pseudomonas aeruginosa and Acinetobacter baumannii are important pathogens and emergence of resistance in these have increased the morbidity and mortality rates. This surveillance study was initiated by the Government of India - Indian Council of Medical Research. The aim of this study is to determine the antimicrobial susceptibility profile and to characterise the enzyme mediated antimicrobial resistance such as extended spectrum beta-lactamases (ESBLs) and carbapenemases among multidrug-resistant (MDR) P. aeruginosa and A. baumannii. MATERIALS AND METHODS: A multi-centric study was conducted from January 2014 to December 2015 with a total number of 240 MDR P. aeruginosa and 312 MDR A. baumannii isolated from blood, cerebrospinal fluid, respiratory, pus, urine and intra-abdominal infections. Kirby-Bauer disc diffusion was done to determine the antimicrobial susceptibility profile. Further, MDR isolates were characterised by multiplex polymerase chain reaction to determine the resistance genes for ESBLs and carbapenemases. RESULTS: Among the ESBLs, blaVEB (23%), blaTEM (5%) and blaSHV (0.4%) in P. aeruginosa and blaPER (54%), blaTEM (16%) and blaSHV (1%) in A. baumannii were the most prevalent. Likewise, blaVIM (37%), blaNDM (14%), blaGES (8%) and blaIMP (2%) in P. aeruginosa and blaOXA-23like (98%), blaOXA-58like (2%), blaNDM (22%) and blaVIM (3%) in A. baumannii were found to be the most prevalent carbapenemases. blaOXA-51like gene, intrinsic to A. baumannii was present in all the isolates tested. CONCLUSION: The data shown highlight the wide difference in the molecular mechanisms of AMR profile between P. aeruginosa and A. baumannii. In P. aeruginosa, plasmid-mediated mechanisms are much lesser than the chromosomal mediated mechanisms. In A. baumannii, class D oxacillinases are more common than other mechanisms. Continuous surveillance to monitor the trends in AMR among MDR pathogens is important for implementation of infection control and to guide appropriate empirical antimicrobial therapy.
Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Farmacorresistencia Bacteriana , Genotipo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , beta-Lactamasas/genética , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/aislamiento & purificación , Cromosomas Bacterianos , Pruebas Antimicrobianas de Difusión por Disco , Genes Bacterianos , Humanos , India , Reacción en Cadena de la Polimerasa Multiplex , Plásmidos , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
OBJECTIVE: To evaluate the utility of brush cytology (BC) in diagnosing non-neoplastic and neoplastic lesions of the upper gastrointestinal (GI) tract. METHODS: The study comprised 106 brushings from 104 patients with clinically suspected lesions in the upper GI tract. Diagnoses were rendered on correlating brush cytological findings with clinicoradiological findings and compared with endoscopic biopsies (EB). An attempt was made to grade oesophageal squamous cell carcinomas (SCC) and to subcategorise gastric adenocarcinomas (AC). The sensitivity, specificity and predictive values of BC were calculated with respect to clinico-radiological outcome. RESULTS: Malignant and benign lesions on BC comprised 74.5% and 25.5%, respectively, and on histology, 64.2% and 28.3%, respectively. Twenty-one of 32 (65.6%) gastric ACs were accurately sub-typed (16 intestinal and five diffuse) and 25/36 (69.4%) oesophageal SCCs (7, 15 and three well, moderately and poorly differentiated, respectively) were accurately graded. On correlation with the final clinico-radiological diagnosis, there was one false-positive and no false-negative cases, respectively, on BC; three false-negative and no false-positive cases, respectively, on EB; eight EB were non-representative in which a diagnosis was not rendered, out of which seven were malignant. Thus, BC had a sensitivity and specificity of 100% and 96.4%, respectively, with a positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of 98.7%, 100% and 99.1% (P Ë 0.05), respectively. BC was superior to EB in detecting Candida species and EB in detecting Helicobacter pylori. CONCLUSIONS: BC is a useful, routinely applicable and reliable test for diagnosing upper GI lesions.
Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Citodiagnóstico , Neoplasias Gastrointestinales/diagnóstico , Adenocarcinoma/patología , Adulto , Anciano , Biopsia , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias Gastrointestinales/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Neoadjuvant chemotherapy has become the standard recommendation in the management of patients with locally advanced breast cancer. At present anthracycline based regimen such as CAF (cyclophosphamide, adriamycin and 5-FU) is widely used in clinical practice. The introduction of taxanes has revolutionized this field because of superior results. AIMS AND OBJECTIVES: This study is designed to compare the efficacy of paclitaxel plus doxorubicin regimen and CAF (cyclophosphamide, doxorubicin and 5-fluorouracil) regimen as neoadjuvant treatment of locally advanced breast cancer and to compare their toxicity profiles and also to correlate the hormonal receptor status in predicting response to the NACT. MATERIALS AND METHODS: In this prospective study, 101 patients with newly diagnosed locally advanced breast cancer were randomized to receive either CAF or Paclitaxel/adriamycin as NACT for three cycles. The response was assessed objectively using CT scans and applying RECIST criteria. The patients were monitored for hematologic, cardiac and other minor toxicities. RESULTS: There was a significantly increased complete and objective response seen in the AP group when compared to CAF group (24% and 58% in the AP group versus 7.8% and 39.2% in the CAF group, P value 0.0313 for complete response). The pCR rate was also significantly higher in the AP group compared to CAF group. (20.93% versus 4.34%, P value 0.0237). There was no significant difference between the groups with respect to cardiotoxicity and hematotoxicity. Patients with ER negative tumors have responded well to neoadjuvant chemotherapy better than ER positive patients. (Objective response 62.8% vs. 40%, P - 0.0473). CONCLUSIONS: Based on these results, taxane based regimen such as Paclitaxel/adriamycin can be recommended as a first line neoadjuvant regimen in patients with locally advanced breast cancer.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Taxoides/uso terapéutico , Adulto , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , India , Persona de Mediana Edad , Centros de Atención TerciariaRESUMEN
BACKGROUND: Two-thirds of surgical site infections (SSI) because of Staphylococcus aureus are caused by Methicillin resistant Staphylococcus aureus (MRSA). This study was done to assess the efficacy of topical 2% mupirocin with 2% chlorhexidine gluconate body wash in decolonizing MRSA and its impact in preventing SSI because of MRSA. The various risk factors associated with MRSA carriers and SSI were also studied because of paucity of data in the developing world. METHODS: We did a non-randomised interventional trial in 602 patients undergoing elective general surgical operations. All patients in case (297) group were screened for MRSA and those positive were decolonised with topical 2% mupirocin calcium ointment and daily baths with 2% chlorhexidine antiseptic solution for 5 days. Control (305) group patients underwent surgery without decolonisation. Postoperatively, all patients were followed up for SSI for 30 days. RESULTS: Prevalence of MRSA carriers was 7.5% with decolonisation rate of 95.2%. The SSI incidence was 21.3%. The significant risk factors for SSI were type of anaesthesia (p = 0.002), duration of surgery (p = 0.001) and preoperative hospital stay (p = 0.001). There was a significant association between MRSA carrier positivity at the time of surgery and SSI (p = 0.041). CONCLUSIONS: There was no reduction in rate of SSI or other nosocomial infections in patients undergoing elective general surgical operations following preoperative MRSA decolonisation with 2% mupirocin and 2% chlorhexidine gluconate in MRSA carriers. MRSA carrier status was a significant risk factor for SSI but not for other nosocomial infections.
Asunto(s)
Infección Hospitalaria , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/epidemiología , Infección de la Herida Quirúrgica/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Antibacterianos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Incidencia , India/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/microbiologíaRESUMEN
Spontaneous choledochoduodenal fistulas (CDFs) are rare. The most common aetiology is penetrating duodenal ulcers, observed in 80% of cases. Even in areas where acid peptic disease is common, tuberculosis should be considered as a cause, especially in developing countries like India, where tuberculosis is common. The management of CDF due to acid peptic disease is predominantly surgical while healing of tuberculous CDF has been reported with antitubercular treatment. A preoperative diagnosis of tuberculous CDF by endoscopic biopsy from the duodenal ulcer or image guided fine needle aspiration if abdominal lymph nodes are present can eliminate the need for surgery and achieve a cure with antitubercular treatment. The CDF in this case was due to caseation of periduodenal lymph nodes rupturing into the duodenum and the bile duct.
Asunto(s)
Fístula Biliar/microbiología , Enfermedades Duodenales/microbiología , Úlcera Duodenal/microbiología , Fístula Intestinal/microbiología , Tuberculosis Gastrointestinal/diagnóstico , Fístula Biliar/cirugía , Enfermedades Duodenales/cirugía , Úlcera Duodenal/cirugía , Endoscopía del Sistema Digestivo/métodos , Humanos , Fístula Intestinal/cirugía , Masculino , Persona de Mediana EdadRESUMEN
Necrotizing soft tissue infections (NSTIs) following elective hernia repair are extremely uncommon, though they can occur following emergency surgery for complicated hernias. They are also usually seen in individuals with impaired immunity. We report a case of fatal necrotizing fasciitis following elective hernia repair in an otherwise healthy young patient. A high index of suspicion is required to diagnose this condition early, as it is difficult to differentiate it from superficial surgical site infection.
Asunto(s)
Procedimientos Quirúrgicos Electivos/efectos adversos , Fascitis Necrotizante/microbiología , Hernia Inguinal/cirugía , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Adulto , Antibacterianos/uso terapéutico , Fascitis Necrotizante/etiología , Fascitis Necrotizante/mortalidad , Resultado Fatal , Humanos , Masculino , Adulto JovenRESUMEN
Primary perineal hernias are rare and can be a diagnostic challenge. We report the case of a 45-year-old female patient who presented with painless perineal swelling suggestive of perineal hernia. Computed tomography (CT) scanning revealed a pelvic mass herniating through the pelvic floor into the perineum. The lesion was completely excised by an abdominoperineal approach. Histopathological examination of the lesion revealed a leiomyoma. This case report suggests that the possibility of perineal herniation of a pelvic leiomyoma should be considered in a female patient with suspected primary perineal hernia. We recommend an abdominoperineal approach for the surgical management of such a lesion.
Asunto(s)
Hernia/diagnóstico por imagen , Leiomioma/diagnóstico por imagen , Perineo/diagnóstico por imagen , Neoplasias Peritoneales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Femenino , Herniorrafia , Humanos , Leiomioma/cirugía , Persona de Mediana Edad , Perineo/cirugía , Neoplasias Peritoneales/cirugíaRESUMEN
The requirement of S-adenosyl-L-methionine (AdoMet) in the cleavage reaction carried out by type III restriction-modification enzymes has been investigated. We show that DNA restriction by EcoPI restriction enzyme does not take place in the absence of exogenously added AdoMet. Interestingly, the closely related EcoP15I enzyme has endogenously bound AdoMet and therefore does not require the addition of the cofactor for DNA cleavage. By employing a variety of AdoMet analogs, which differ structurally from AdoMet, this study demonstrates that the carboxyl group and any substitution at the epsilon carbon of methionine is absolutely essential for DNA cleavage. Such analogs could bring about the necessary conformational change(s) in the enzyme, which make the enzyme proficient in DNA cleavage. Our studies, which include native polyacrylamide gel electrophoresis, molecular size exclusion chromatography, UV, fluorescence and circular dichroism spectroscopy, clearly demonstrate that the holoenzyme and apoenzyme forms of EcoP15I restriction enzyme have different conformations. Furthermore, the Res and Mod subunits of the EcoP15I restriction enzyme can be separated by gel filtration chromatography in the presence of 2 M NaCl. Reconstitution experiments, which involve mixing of the isolated subunits, result in an apoenzyme form, which is restriction proficient in the presence of AdoMet. However, mixing the Res subunit with Mod subunit deficient in AdoMet binding does not result in a functional restriction enzyme. These observations are consistent with the fact that AdoMet is required for DNA cleavage. In vivo complementation of the defective mod allele with a wild-type mod allele showed that an active restriction enzyme could be formed. Furthermore, we show that while the purified c2-134 mutant restriction enzyme is unable to cleave DNA, the c2-440 mutant enzyme is able to cleave DNA albeit poorly. Taken together, these results suggest that AdoMet binding causes conformational changes in the restriction enzyme and is necessary to bring about DNA cleavage.