Laboratory variables as predictors of progression in gastroenteropancreatic neuroendocrine tumors in different lines of antineoplastic treatments

ABSTRACT Objective: To determine the association of red cell blood counts, and liver panel tests to predict outcomes in patients with gastroenteropancreatic neuroendocrine tumors who underwent systemic antineoplastic treatments. Methods: Patients with gastroenteropancreatic neuroendocrine tumors in systemic treatment were assessed according to laboratory tests within the same period. Progression free survival was determined by the period between the beginning of treatment and the date of progression. We used conditional models (PWP model) to verify the association between laboratory tests and tumor progression. The level of significance used was 5%. Results: A total of 30 treatments given to 17 patients in the intention-to-treat population were evaluated. Treatment included octreotide, lanreotide, everolimus, lutetium, and chemotherapy. We had statistically significant results in chromogranin A, neutrophils and platelets-to-lymphocyte ratio. The risk of progression increases by 2% with the addition of 100ng/mL of chromogranin A (p=0.034), 4% with the increase of 100 neutrophil units (p=0.006), and 21% with the addition of 10 units in platelets-to-lymphocyte ratio (p=0.002). Conclusion: Chromogranin A, neutrophils and platelets-to-lymphocyte ratio were associated with disease progression during systemic treatment in gastroenteropancreatic neuroendocrine tumors. Further prospective studies with larger cohorts are necessary to validate our findings.

Effect of implementation intention on walking in people with diabetes: an experimental approach

ABSTRACT OBJECTIVE To evaluate the effect of implementation intentions as an intervention strategy to promote walking in adults with type 2 diabetes mellitus (T2DM). METHODS We conducted a controlled and randomized trial, with 12 months of follow-up, involving 65 people with T2DM recruited from primary health care units and allocated them in the control group (CG, n = 32) and intervention group (IG, n = 33). The IG received the implementation intention strategy to promote walking and the CG remained in follow-up for conventional treatment in primary health care. The researchers were blinded by anthropometric measurements and the filling of the instruments. RESULTS After twelve months of follow up, the IG presented a statistically significant increase in the leisure time physical activity when compared with the CG (p = 0.0413) and showed a significant decrease in waist circumference (p = 0.0061). No significant difference was observed regarding body mass index and glycated hemoglobin among groups. CONCLUSIONS Implementation intention was effective in promoting walking and improving clinical indicators in adults with T2DM.

Causas de pérdidas de pacientes durante los ensayos clínicos con asignación aleatoria: estudio metaepidemiológico / Causes of patient loss during clinical trials: a meta-epidemiological study

RESUMEN Objetivo: Los ensayos clínicos controlados aleatorizados representan el estudio de elección para evaluar la seguridad y la eficacia de intervenciones contra problemas de salud. La validez interna de estos se puede ver afectada por las frecuentes pérdidas de pacientes que se presentan. El objetivo de este estudio es describir cuáles son las principales causas de pérdidas de pacientes durante los ensayos clínicos en el área de medicina, si hay diferencias según el grupo al que pertenezcan y si se realizó análisis por intención a tratar. Metodología: Estudio observacional descriptivo. Se escogió una muestra por conveniencia de 100 ensayos clínicos controlados relacionados con el área de medicina, publicados en los últimos cinco años (2011- 2016), de cuatro revistas de alto impacto científico, y se identificaron las principales causas de pérdidas de pacientes. Resultados: Se revisó un total de 100 artículos de medicina. Se identificaron 15 causas de pérdidas de pacientes durante los ensayos clínicos; las tres más prevalentes según el número de pacientes fueron pérdida del seguimiento (61.42%), descontinuación de la intervención (25.28%), y muerte (2.34%). Las tres más frecuentes según el número de ensayos clínicos fueron pérdida del seguimiento (73%), retiro (34%), y muerte (31%). En el 36% de los ensayos clínicos analizados se empleó un análisis por intención de tratar. Conclusión: En el total de ensayos clínicos revisados se observó que la causa más prevalente de pérdida de pacientes fue la pérdida en el seguimiento. Asimismo, el análisis por intención de tratar se empleó en aproximadamente un tercio de los artículos revisados.

ABSTRACT Objective: Randomized controlled clinical trials represent the study of choice to evaluate the safety and effectiveness of interventions against any health problems. The internal validity of these can be affected by the frequent losses of patients. The main objective of the study is to describe what are the main causes of loss of patients during clinical trials in the area of medicine in four major medical journals of high impact factor, if there are differences according to the group that they belong and if the authors performed the intention to treat analysis. Methods: Descriptive observational study. A convenience sample of 100 controlled clinical trials, related to the area of medicine was selected, the articles were published in the last five years (2011- 2016), of four journals of high scientific impact, in which the main causes of loss of patients were identified. Outcomes: A total of 100 articles of internal medicine were reviewed. We identified 15 causes of patient losses during clinical trials; the three most prevalent according to the number of patients were loss of follow-up (61.42%), discontinuation of the intervention (25.28%), and death (2.34%). The three most frequent according to the number of clinical trials were loss of follow-up (73%), retirement (34%) and death (31%). An analysis by intention to treat was used in 36% of the clinical trials analyzed. Conclusion: In the total of reviewed clinical trials, the most frequent cause of loss of patients was loss of follow-up. Furthermore, the intention to treat analysis was used in about one third of the articles reviewed.

Eradication Rates of 10-day Sequential Therapy for Helicobacter pylori: Results of an 8-year Prospective Study Conducted at a Tertiary Korean Hospital / 대한소화기학회지

BACKGROUND/AIMS: The Helicobacter pylori (H. pylori) eradication rate of standard triple therapy is unsatisfactory in Korea, and sequential therapy (SQT) has been suggested to be a practical first-line alternative regimen. The aim of this prospective study was to document changes in annual eradication rates of SQT. METHODS: A total of 983 H. pylori-positive subjects were enrolled from 2010 to 2018 and their data were subjected to intention-to-treat (ITT) and per-protocol (PP) analysis. All subjects received 10-day sequential therapy consisting of 40 mg esomeprazole and 1 g amoxicillin b.i.d for 5 days followed by 40 mg esomeprazole b.i.d, 500 mg clarithromycin b.i.d and 500 mg metronidazole t.i.d for 5 days. The 13C-urea breath test, rapid urease test (CLO test®), and histology were used to confirm eradication. Compliance and side effects were also investigated. RESULTS: ITT and PP eradication rates of SQT were 69.9% (687 of 983) and 87.1% (657 of 754), respectively. The annual eradication rate of ITT remained consistent over the 8-year study period (p for trend=0.167), whereas PP analysis showed the eradication rate increased (p for trend=0.042). The overall adverse event rate for SQT was 41.7% (410 subjects). CONCLUSIONS: Despite high antibiotic resistance rates in Korea, the eradication rate of SQT did not decrease over the 8-year study period.

Statistical issues in randomised controlled trials: A narrative synthesis

ABSTRACT: Randomised controlled trials (RCT s) are gold standard in the evaluation of treatment efficacy in medical investigations, only if well designed and implemented. Till date, distorted views and misapplications of statistical procedures involved in RCTs are still in practice. Hence, clarification of concepts and acceptable practices related to certain statistical issues involved in the design, conduct and reporting of randomised controlled trials is needed. This narrative synthesis aimed at providing succinct but clear information on the concepts and practices of selected statistical issues in RCT s to inform correct applications. The use of tests of significance is no longer acceptable as means to compare baseline similarity between treatment groups and in determining which covariate(s) should be included in the model for adjustment. Distribution of baseline attributes simply presented in tabular form is however, rather preferred. Regarding covariate selection, such approach that makes use of information on the degree of correlation between the covariate(s) and the outcome variable is more in tandem with statistical principle(s) than that based on tests of significance. Stratification and minimisation are not alternatives to covariate adjusted analysis; in fact they establish the need for one. Intention-to-treat is the preferred approach for the evaluation of primary outcome measures and researchers have responsibility to report whether or not the procedure was followed. A major use of results from subgroup analysis is to generate hypothesis for future clinical trials. Since RCT s are gold standard in the comparison of medical interventions, researchers cannot afford the practices of distorted allocation or statistical procedures in this all important experimental design method.

Triple and Quadruple Eradication Therapy for H. pylori in Iraqi Patients with Peptic Ulcer Disease a Comparative Study.

The eradication of H. pylori has become an important issue; since Helicobacter pylori infection can cause chronic gastritis, peptic ulcer, gastric cancer and (MALT) lymphoma. Standard triple therapy efficacy has decreased gradually worldwide during the last decade and quadruple therapy is recommended as an alternate treatment option for the management of H. pylori. The aim of this study was to compare between triple and quadruple therapy for eradication of H. pylori in Iraqi patients with peptic ulcer disease, and to treat the patients who relapsed after triple therapy. In addition to that; response to therapy (triple and quadruple) have been evaluated according to the Body Mass Index (BMI). A prospective case controlled study was carried on 60 patients who had peptic ulcer disease and positive H. pylori infection confirmed by (histology; stool antigen test and anti-H. pylori IgG antibody test) patients were divided into 3 groups first group involved 38 patients treated with triple therapy (500 mg clarithromycin capsules; 1 g amoxicillin capsules; and 20 mg esomeprazole capsules) for 14 days. The second group involved 22 patients treated with quadruple therapy (pylera)®; (140 mg bismuth sub citrate potassium, 125 mg metronidazole, and 125 mg tetracycline hydrochloride) for 10 days, while third group involved patients un responding to triple therapy treated with secondline quadruple therapy for 10 days. The results showed that the eradication rate of the per-protocol and intention-to-treat for quadruple therapy was 88.57%, 83.78% respectively which was more than 57.89% per-protocol and 50% intention-to-treat for standard triple therapy with high significant difference (p<0.01). Patients compliance with quadruple and triple therapy was good for the two regimens in spite of the more adverse effect of quadruple regimen compared to triple regimen. On conclusion; the 10 days treatment with quadruple therapy was more effective than 14 days triple therapy that could be attributed to more eradication rate for H. pylori.

A prospective, open, comparative study of 5% potassium hydroxide solution versus cryotherapy in the treatment of genital warts in men

BACKGROUND: Genital warts are caused by human papillomavirus infection and represent one of the most common sexually transmitted diseases. Many infections are transient but the virus may recur, persist, or become latent. To date, there is no effective antiviral treatment to eliminate HPV infection and most therapies are aimed at the destruction of visible lesions. Potassium hydroxide is a strong alkali that has been shown to be safe and effective for the treatment of genital warts and molluscum contagiosum. Cryotherapy is considered one of the most established treatments for genital warts. No comparative trials have been reported to date on the use of potassium hydroxide for genital warts. OBJECTIVE: A prospective, open-label, randomized clinical trial was conducted to compare topical potassium hydroxide versus cryotherapy in the treatment of genital warts affecting immunocompetent, sexually active men. METHODS: Over a period of 10 months, 48 patients were enrolled. They were randomly divided into two groups and selected on an alternative basis for either potassium hydroxide therapy or cryotherapy. While response to therapy did not differ substantially between both treatment modalities, side effects such as local pain and post-treatment hypopigmentation were considerably more prevalent in the groups treated using cryotherapy. Result: In our study, potassium hydroxide therapy proved to be at least as effective as cryotherapy and offered the benefit of a better safety profile. CONCLUSION: Topical 5% potassium hydroxide presents an effective, safe, and low-cost treatment modality for genital warts in men and should be included in the spectrum of therapies for genital warts. .

Vocal analysis of suicidal movie characters / Análise vocal de personagens suicidas de filmes de cinema

OBJECTIVE: The aim of this study was to describe the auditory-perceptive evaluation and the psychodynamic aspects of voice samples among suicidal movie characters. METHOD: Voice samples of 48 characters (27 male, 21 female), extracted from 36 movies produced between 1968 and 2006, were analyzed. The samples were evaluated through a specific protocol focusing on the auditory-perceptive evaluation (voice quality, resonance, pitch, loudness, modulation, pauses, articulation and rhythm) and the psychodynamic aspects of voice. RESULTS: 85.5 percent of the samples exhibited abnormal findings in at least five parameters of the auditory-perceptive analysis, such as breathiness (n = 42; 87.5 percent of the samples), hoarseness (n = 39; 81.2 percent) and strain (n = 29; 60.4 percent), as well as laryngopharingeal resonance (n = 39; 81.2 percent), either high pitch (n = 14; 29.2 percent), or decreased loudness (n = 31; 64.6 percent). With respect to the psychodynamic aspects, dismay was detected in 50 percent (n = 24) of the samples, hopelessness in 47.9 percent (n = 23), resignation in 37.5 percent (n = 18), and sadness in 33.3 percent (n = 16). CONCLUSION: Our findings suggest the existence of specific patterns used by actors during the interpretation of suicidal characters. The replication of these findings among real patients may contribute to improvement in the evaluation of potential suicidal patients, as well as the implementation of preventive measures.

OBJETIVO: O objetivo do presente estudo foi descrever a análise perceptivo-auditiva e de psicodinâmica vocal de amostras de fala de personagens suicidas em filmes de cinema. MÉTODO: Foram analisadas amostras de fala de 48 personagens suicidas (27 homens, 21 mulheres), extraídas de 36 filmes produzidos no período de 1968 a 2006. As amostras foram analisadas utilizando-se um protocolo especificamente produzido para o registro das características da voz por meio da análise perceptivo-auditiva (qualidade vocal, ressonância, pitch, loudness, modulação, pausas, articulação e ritmo de fala) e da psicodinâmica vocal. RESULTADOS: 85,5 por cento das amostras (n = 41) apresentaram alterações em ao menos cinco parâmetros da análise perceptivo-auditiva, com destaque para soprosidade (n = 42; 87,5 por cento das amostras), rugosidade (n = 39; 81,2 por cento) e tensão (n = 29; 60,4 por cento), bem como ressonância laringofaríngea (n = 39; 81,2 por cento), pitch agudo (n = 14; 29,2 por cento) e loudness fraca (n = 31; 64,6 por cento). A análise da psicodinâmica vocal revelou desânimo em 50 por cento (n = 24) das amostras, desesperança em 47,9 por cento (n = 23), resignação em 37,5 por cento (n = 18) e tristeza em 33,3 por cento (n = 16). CONCLUSÃO: Os achados do presente estudo apontam para padrões vocais característicos utilizados por atores na interpretação de personagens suicidas. Se replicados entre pacientes reais, estes achados podem contribuir para o aperfeiçoamento da avaliação do risco de suicídio e a instauração de medidas preventivas.

Double-Blind Placebo-Controlled Randomized Clinical Trial of Topiramate Add-On Therapy in Medically Intractable Partial Epilepsies

BACKGROUND: To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies. METHODS: This study was a multicenter double-blind placebo-controlled randomized parallel group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of maintenance phase. The primary efficacy variable was the median seizure frequency reduction rate(MSFRR) and the other efficacy variables included responder rate, seizure free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs(AEDs) and should have at least two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600mg/day. The study drug was started at the initial dose of 50mg/day and increased by 50mg/day every week until 400mg/day was reached. Thereafter, the dose was increased by 100mg weekly over next two weeks. RESULTS: A total of 177 patients were randomized into TPM group(n=91) and placebo (PLC) group (n=86). Baseline median seizure frequencies were 5.60 episodes/4 weeks in TPM group and 5.59 episodes/4 weeks in PLC group. Among those who were randomized, 158 patients (TPM: 78 patients, PLC: 80 patients) were available for efficacy measurement by intention-to-treat analysis. The MSFRR was 63.6% for TPM and 17.9% for PLC, which was highly in favor of TPM (p=0.0001). The responder rate was 59.0% for TPM and 23.8% for PLC (p=0.001). Thirteen of 78 patients (16.7%) taking TPM became seizure free compared to 2 of 80 patients (2.5%) taking PLC (p=0.004). The global evaluation by the patient and the physician greatly favored TPM (p=0.001, p=0.001). The incidence of adverse events(AE) was higher in TPM(81.3%) than PLC (48.9%) with CNS-related AE being the most frequent. Among individual AE, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AE in TPM group. AE precipitated early drop out in 7 patients taking TPM (7.6%) and 3 patients taking PLC(3.5%). No serious AE were observed. CONCLUSIONS: TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM seems to decrease the drop-out rate but the incidence of AE was still high. The AE profile of TPM in Asians was different from that in Caucasians.