Effects of Age Among Elderly Cancer Patients on Breakthrough Pain Management with Sublingual Fentanyl Tablets.

INTRODUCTION: Sublingual fentanyl tablets (SFTs) have been shown to be a safe and effective option in controlling breakthrough cancer pain (BTcP). However, further examination is required to investigate the use of SFTs among the elderly. The aim of this study was to examine the influence of age in BTcP management with SFTs in the elderly population. METHODS: We performed subgroup analyses of a recently completed trial in two subsets of individuals: patients aged 65-74 years (low age group) and patients ≥ 75 years (high age group). Pain intensity (PI), onset of pain relief, frequency and duration of BTcP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health status instruments used were the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and the Short Form 12, version 2 (SF-12v2) questionnaire. RESULTS: Levels of PI at the end of the study improved significantly as compared with baseline in both the low and the high age groups (30.0% and 27.7% reduction, respectively). The onset of analgesia at the end of the study began in < 10 min in 85.0% of young-old subjects and in 62.5% of patients ≥ 75 years, but no significant differences were found. BTcP episodes lasted < 15 min in 75.0% of patients in the low age group and 58.3% in the high age group (p = 0.24). Most of patients in both groups experienced one to five BTcP daily episodes, at all assessment points. HADS-D decreased from 10.78 (± 4.33) to 8.21 (± 3.57) in the low age group, and from 10.96 (± 4.26) to 9.36 (± 3.35) in the high age group (p = 0.02). Significant differences in HADS-A scores from baseline to the end of the study were also observed in both subgroups (p < 0.05). Patients in the low age group had less favorable mental component summary (MCS) and physical component summary (PCS) scores than patients in the high age group. At the end of the study, 10.0% of young-old patients and 29.2% of patients aged ≥ 75 years reported AEs related to their treatment. The most commonly reported AEs included nausea, vomiting, constipation, somnolence, and skin disorders and they were generally mild to moderate in severity. CONCLUSIONS: The results of this study showed that SFTs provided safe and clinically meaningful pain relief in both elderly subgroups. Clinical implications of these findings await validation in large, confirmatory studies to identify age subgroup divergences among elderly cancer patients treated with SFTs.

Correction to: Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain Management According to Cancer Stage and Background Opioid Medication.

In the Original Publication.

Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain Management According to Cancer Stage and Background Opioid Medication.

OBJECTIVE: Our objective was to assess the effect of sublingual fentanyl tablets (SFTs) on pain relief, quality of life, and adverse effects in patients with cancer pain, according to cancer stage and background opioid regimen. METHODS: Subgroup analyses from a recently completed study were performed according to cancer stage (locally advanced cancer [LAC] vs. metastatic cancer) and most frequent background opioid medication (fentanyl vs. oxycodone/naloxone). The efficacy and safety of SFTs were evaluated, recording pain intensity (PI), onset of pain relief, and adverse events (AEs). Health status was assessed with the Short Form 12, version 2 (SF-12v2) questionnaire and the Hospital Anxiety and Depression Scale (anxiety subscale [HADS-A] and depression subscale [HADS-D]). RESULTS: In total, 54 (67.5%) patients had LAC and 26 (32.5%) had metastatic cancer. The oxycodone/naloxone group included 39 patients (48.1%) and the fentanyl group 29 (35.8%). In all subgroups, pain relief was achieved within 5 min in an increasing number of individuals over time; at the end of the study, PI values decreased (PI-end: 44.4% for LAC vs. 57.9% for metastatic cancer; 44.4% for fentanyl vs. 38.6% for oxycodone/naloxone). HADS and mental component summary (MCS) SF-12v2 scores significantly improved in the LAC group (HADS-A 9.44-8.04; HADS-D 10.46-8.15; MCS 44.69-45.94) and in the fentanyl group (HADS-A 10.05-8.33; HADS-D 11.95-8.76; MCS 44.38-47.19). AEs were reported in few patients and were mostly mild. CONCLUSIONS: Exploratory subgroup analyses show the efficacy and safety of SFTs for the treatment of breakthrough pain in patients with cancer, regardless of their cancer stage and background opioid medication.

Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.

INTRODUCTION: Breakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories. METHODS: We performed age subgroup analyses (<65 and ≥65 years) from a recently completed study conducted in Spain. Pain intensity (PI), onset of pain relief, frequency and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF-12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D). RESULTS: Twenty-six patients were aged <65 years and 54 were aged ≥65 years. SF-12v2 scores did not enhance significantly from baseline. HADS scores and PI decreased significantly at the end of the study, particularly in younger patients (HADS-A: 19.05 vs. 14.41%; HADS-D: 21.35 vs. 18.57%; PI: 67.23 vs. 56.30%). Onset of analgesia began in 2-5 min in 63.3% of subjects aged <65 years and in 36.4% of subjects aged >65 years. Most patients experienced one to five daily episodes after 30 days, and <5% needed a treatment change. AEs were less frequently reported in older individuals (20.5 vs. 36.4%). CONCLUSION: Age subgroup analyses suggest that SFTs are an effective and safe treatment for the management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated and efficient option to control cancer BTP in the elderly.

Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes.

BACKGROUND AND OBJECTIVE: Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. METHODS: We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30 days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. RESULTS: Of the 102 patients considered eligible, 81 (79.4 %) were enrolled; of these, 69 (85.1 %) completed the study. Significant pain reduction was achieved for average PI (p < 0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p = 0.005) and the anxiety subscale (p < 0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p < 0.001) and the physical component score (p = 0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. CONCLUSION: SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.

Efficacy and safety of sublingual fentanyl orally disintegrating tablets in patients with breakthrough pain: multicentre prospective study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effectiveness and safety of sublingual fentanyl oral disintegrating tablets (sublingual fentanyl ODT) for the treatment of breakthrough pain (BTP), cancer or non-cancer related, in terms of relief of pain intensity, adverse events (AEs) and patient satisfaction, and to further examine the clinical and epidemiological profile of patients with BTP in a clinical setting. METHODS: A multicentre, prospective, open-label study was conducted in 19 pain units from Catalonia hospitals (Spain) over a 1-month period. Opioid-tolerant adult patients experiencing episodes of BTP intensity >5 on a visual analogue scale (VAS) during the 12-24 h before screening or AEs related to their previous rescue medication for BTP received sublingual fentanyl ODT in the course of routine clinical practice and completed a 30-day study period consisting of five assessment points: days 0 (baseline), 3, 7, 15 and 30. The efficacy was assessed by collecting pain intensity and pain relief data at baseline and at each assessment. AEs were recorded by investigators throughout the study during clinic visits and telephone follow-ups. For all patients, titration was begun with an initial dose of 100 µg. No more than two doses were allowed to treat an episode and patients might wait at least 4 h before treating another BTP episode with sublingual fentanyl ODT. The dose was increased by 100 µg multiples up to 400 µg as needed; and by 200 µg multiples up from 400 to 800 µg, the maximum titration step. RESULTS: A total of 182 patients were enrolled and 177 (97.2 %) completed the study: 37 had breakthrough cancer pain (BTcP) and 145 had breakthrough non-cancer pain (BTncP). The mean pain intensity showed a statistically significant improvement at the first assessment point and at all assessments thereafter (p < 0.0001). At the end of the study, the time lag between administration and first effect of sublingual fentanyl ODT was ≤10 min in 69.0 % (60 % BTcP and 71.2 % BTncP). The number of daily BTP episodes decreased in both groups, but it was statistically significant in BTcP. 114 patients (62.64 %) experienced AEs during the study. AEs recorded included nausea, vomiting, somnolence and constipation, and seven (4.49 %) were considered severe. No death or discontinuation was considered related to AEs. CONCLUSION: Sublingual fentanyl ODT provided rapid and consistent relief from BTP, both in cancer and non-cancer patients. It was well-tolerated and well-accepted by patients in routine clinical practice.

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

BACKGROUND: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. AIM: To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. DESIGN: Prospective multicenter study. PATIENTS: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. INTERVENTION: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME: Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Asistencia urgente a los pacientes con hemorragia digestiva alta en los hospitales comarcales catalanes / Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia

Objetivo Valorar los recursos disponibles en los hospitales comarcales catalanes para la asistencia urgente de la hemorragia digestiva alta. Método Se analiza una encuesta enviada a 32 hospitales, sobre la existencia, composición y recursos del turno de guardia (TDG) de endoscopia, referida al año 2009.ResultadosRespondieron 24 centros, que cubrían la asistencia de 3.954.000 habitantes. Tenían TDG 12 hospitales. No disponían de TDG en su centro de referencia 1.483.000 habitantes. Los centros con TDG tenían más camas y cubrían más población. Los TDG estaban formados por 4,5 endoscopistas (rango 2-11), que cubrían 82,1 (33,2-182,5) guardias/año. Diecisiete centros reportaban 1.571 episodios (51 por centro, rango 3-280, 39,68/100.000 hab.). Los centros con TDG reportaban más casos (76 vs. 43, p=0,047). Los que no disponen de TDG derivaron más pacientes (147 vs. 17, p= 0,001). Los pacientes en urgencias estaban a cargo de medicina interna en 4 centros, de cirugía en 14 y repartidos entre ambos servicios en 6. Si ingresaban, quedaron a cargo de Digestivo solo en 6 hospitales. Los recursos más utilizados eran la ligadura en la hemorragia varicosa y las terapias de inyección en la no varicosa. Un 21% de centros no realizaban tratamiento combinado. Conclusiones Una proporción significativa de la población no dispone de endoscopista de guardia en su centro de referencia. La constitución de TDG en hospitales comarcales supone importantes cargas asistenciales. La coordinación entre profesionales y centros permitiría la aplicación eficiente de los recursos terapéuticos y el establecimiento de TDG en centros que no tienen (AU)

Objective To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage. Methods We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009.ResultsResponses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment. Conclusions A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource (AU)

[Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia]. / Asistencia urgente a los pacientes con hemorragia digestiva alta en los hospitales comarcales catalanes.

OBJECTIVE: To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage. METHODS: We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009. RESULTS: Responses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment. CONCLUSIONS: A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource.

Colonoscopic perforation: useful parameters for early diagnosis and conservative treatment.

OBJECTIVE: The purpose of this study is to determine useful parameters for the early diagnosis of colonoscopic perforation and to select those who would require surgical treatment. METHODS: We retrospectively reviewed the demographics, clinical and colonoscopic data, diagnostic-surgical interval, operative findings, complications, and hospital stay of patients who developed postcolonoscopy iatrogenic colonic perforation between January 2002 and December 2008. RESULTS: A retrospective multicentric study of patients diagnosed of colonoscopic perforation was performed. Fifty-four patients were found for final analysis (mean age, 71 years (26-91 years). Thirty-four were diagnostic and 20 were therapeutic colonoscopies. Most patients in whom the perforation was noticed during colonoscopy were treated surgically (p = 0.032) within 24 h (p = 0.004) and had a lesser degree of surgical peritonitis (p = 0.033). Those with deficient bowel preparation had more interventions (p < 0.05), ostomies (p = 0.015), and complications (p = 0.023) as well as major clinical (p < 0.001) and surgical peritonitis (p = 0.031). Patients with nonoperative management had fewer complications (p = 0.011) and lower hospital stay (p < 0.048). Surgical treatment within 24 h resulted in a lesser degree of surgical peritonitis (p < 0.001), fewer intestinal resections (p < 0.001), ostomies (p = 0.002) and complications (p < 0.047), and shorter hospital stay (p < 0.05). CONCLUSIONS: We recommend a conservative treatment for patients with the following conditions: good general health, unnoticed perforation during endoscopy, early diagnosis, no signs of diffuse peritonitis, proper colonic preparation, and a different injury mechanism to traction. Patients treated surgically after the first 24 h are likely to have a greater degree of peritonitis and more intestinal resections, ostomies, and complications.

A rapid and reliable direct method for quantifying meat acylglycerides with monomode microwave irradiation.

A rapid methodology for direct analysis of meat acylglycerides is proposed. A transesterification is carried out in a microwave reactor consisting of a monomode oven using chlorotrimethylsilane (CTMS) and methanol. High-temperature gas chromatography was used to check the absence of underivatized acylglycerides. Whereas transesterification is complete after 30s at 90 degrees C in the microwave method, the reference method needs 2h to complete this process. Moreover, the CTMS-microwave method shows higher recoveries of individual saturated, monounsaturated and polyunsaturated fatty acids. No influence of microwave irradiation on the composition of the fatty acids was observed.

Second-line rescue therapy with levofloxacin after H. pylori treatment failure: a Spanish multicenter study of 300 patients.

AIM: Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. DESIGN: Prospective multicenter study. PATIENTS: in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. INTERVENTION: A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. CONCLUSION: Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.