New Perspectives on the Adverse Effects of NSAIDs in Cancer Pain: An Italian Delphi Study from the Rational Use of Analgesics (RUA) Group.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs for cancer pain. We used the Delphi methodology to evaluate the opinions of clinicians on NSAIDs and paracetamol, with a specific focus on their safety profile. Consensus was reached on seven statements. A high level of consensus was reached regarding the use of NSAIDs and gastrointestinal, cardiovascular, and renal risk in patients taking low-dose aspirin and assessment of liver function during long-term treatment with paracetamol. Consensus was also reached that assessment and monitoring of eGFR are important in the elderly being administered NSAIDs. It was further agreed that NSAIDs can often play a key role in association with opioids in the treatment of cancer pain and that paracetamol is the analgesic of first choice for patients with mild chronic pain. When NSAIDs are administered in combination with steroids, it was agreed that the risk of gastrointestinal damage is increased since steroids delay the healing of ulcers and that paracetamol can be used during pregnancy and does not affect the health of the fetus. This Delphi study highlights that there is poor agreement on how these drugs are routinely prescribed. However, a consensus was reached for seven key statements and may represent a valid contribution to daily practice.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Careful Breakthrough Cancer Pain Treatment through Rapid-Onset Transmucosal Fentanyl Improves the Quality of Life in Cancer Patients: Results from the BEST Multicenter Study.

OBJECTIVES: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. METHODS: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Stable chronic background pain (numeric rating scale, NRS ≤ 4) during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). RESULTS: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (linear p-value = 0.1) and dyspnea (Linear p-value = 0.05). The ESAS and PSQI questionnaires confirmed these positive results (p < 0.0001 and p = 0.002, respectively). CONCLUSIONS: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance.

Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS).

INTRODUCTION: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. METHODS: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. RESULTS: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. CONCLUSIONS: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. FUNDING: Molteni Farmaceutici, Italy.

Background and episodic breathlessness in advanced cancer patients followed at home.

BACKGROUND: The aim of this study was to assess the phenomenon of episodic breathlessness in advanced cancer patients followed by palliative care services at home. METHODS: A consecutive sample of patients with advanced cancer, admitted to home care for a period of six months, was surveyed. The presence of background breathlessness and episodic breathlessness, their intensity, and drugs used for their treatment were collected. Factors inducing episodic breathlessness, and its influence on daily activities were investigated. RESULTS: Three hundred forty-seven advanced cancer patients admitted to home palliative care were surveyed. The prevalence of breathlessness was 35.3%. The mean intensity of breathlessness was 3.8 (SD 1.96), out of a maximum score of 10 for worst imaginable. Sixty patients (49.2%) were receiving drugs for background breathlessness. In the multivariate analysis the risk of breathlessness increased with cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer while it decreased in patients with a better performance status. The prevalence of episodic breathlessness in patients with background breathlessness was 79.5% and its mean intensity was 7.1 (SD 1.5, range 2-10). The mean duration of episodic breathlessness was 28.6 minutes (SD 47.1, range 1-300 minutes). Forty-three patients (44.3%) were receiving one or more drugs as needed. The majority of episodic breathlessness events were triggered by activity. Episodic breathlessness was interfering with daily activities in 65 patients (67%). Episodic breathlessness wasn't associated with any variable taken into consideration. CONCLUSION: This study showed that episodic breathlessness frequently occurs in advanced cancer patients admitted to home care, is severe in intensity, is triggered in most cases by activity, and is characterized by a short duration which requires rapid measures.

Validity, reliability and responsiveness to change of the Italian palliative care outcome scale: a multicenter study of advanced cancer patients.

BACKGROUND: There is an increasing requirement to assess outcomes, but few measures have been tested for advanced medical illness. We aimed to test the validity, reliability and responsiveness of the Palliative care Outcome Scale (POS), and to analyse predictors of change after the transition to palliative care. METHODS: Phase 1: multicentre, mixed method study comprising cognitive and qualitative interviews with patients and staff, cultural refinement and adaption. Phase 2: consecutive cancer patients on admission to 8 inpatient hospices and 7 home-based teams were asked to complete the POS, the EORTC QLQ-C15-PAL and the FACIT-Sp (T0), to assess internal consistency, convergent and divergent validity. After 6 days (T1) patients and staff completed the POS to assess responsiveness to change (T1-T0), and agreement between self-assessed POS and POS completed by the staff. Finally, we asked hospices an assessment 24-48 h after T1 to assess its reliability (test re-test analysis). RESULTS: Phase I: 209 completed POS questionnaires and 29 cognitive interviews were assessed, revisions made and one item substituted. Phase II: 295 consecutive patients admitted to 15 PCTs were approached, 175 (59.3 %) were eligible, and 150 (85.7 %) consented. Consent was limited by the severity of illness in 40 % patients. We found good convergent validity, with strong and moderate correlations (r ranged 0.5-0.8) between similar items from the POS, the QLQ-C15-PAL and the FACIT-Sp. As hypothesised, the physical function subscale of QLQ-C15-PAL was not correlated with any POS item (r ranged -0.16-0.02). We found acceptable to good test re-test reliability in both versions for 6 items. We found significant clinical improvements during the first week of palliative care in 7/10 items assessed-pain, other symptoms, patient and family anxiety, information, feeling at peace and wasted time. CONCLUSIONS: Both the patient self-assessed and professional POS versions are valid and with an acceptable internal consistency. POS detected significant clinical improvements during palliative care, at a time when patients are usually expected to deteriorate. These results suggest that there is room for substantial improvement in the management of patients with advanced disease, across all key domains-symptoms, psychological, information, social and spiritual.

Epidemiology and Characteristics of Episodic Breathlessness in Advanced Cancer Patients: An Observational Study.

CONTEXT: Episodic breathlessness is a relevant aspect in patients with advanced cancer. OBJECTIVES: The aim of this study was to assess the different aspects of this clinical phenomenon. METHODS: A consecutive sample of patients with advanced cancer admitted to different settings for a period of six months was surveyed. The presence of background breathlessness and episodic breathlessness, their intensity (numerical scale 0-10), and drugs used for treatment were collected. Factors inducing episodic breathlessness and its influence on daily activities were investigated. RESULTS: Of 921 patients, 29.3% (n = 269) had breathlessness and 134 patients (49.8%) were receiving drugs for background breathlessness. In the multivariate analysis, the risk of breathlessness increased with chronic obstructive pulmonary disease, although it decreased in patients receiving disease-oriented therapy and patients with gastrointestinal tumors. The prevalence of episodic breathlessness was 70.9% (n = 188), and its mean intensity was 7.1 (SD 1.6). The mean duration of untreated episodic breathlessness was 19.9 minutes (SD 35.3); 41% of these patients were receiving drugs for episodic breathlessness. The majority of episodic breathlessness events (88.2%) were triggered by activity. In the multivariate analysis, higher Karnofsky Performance Status levels were significantly related to episodic breathlessness, although patients receiving disease-oriented therapy were less likely to have episodic breathlessness. CONCLUSION: This study showed that episodic breathlessness frequently occurs in patients with breathlessness in the advanced stage of disease, has a severe intensity, and is characterized by rapid onset and short duration, which require rapid measures.

Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.

BACKGROUND: Oral symptoms can be a sign of an underlying systemic condition and have a significant impact on quality of life, nutrition, and cost of care, while these lesions are often studied in the context of cancer treatment. However, information regarding oral symptoms in advanced cancer patients is poor. The aim of this multicenter study was to determine the prevalence and the characteristics of oral symptoms in a large population of advanced cancer patients. METHODS: A consecutive sample of patients with advanced cancer for a period of 6 months was prospectively assessed for an observational study. At time of admission, the epidemiological characteristics, surgery-radiotherapy of head and neck, and oncologic treatments in the last month were recorded. The presence of mucositis, dry mouth, and dysphagia was assessed by clinical examination and patients' report and their intensity recorded. Patients were also asked whether they had limitation on nutrition of hydration due to the local condition. RESULTS: Six hundred sixty-nine patients were surveyed in the period taken into consideration. The mean age was 72.1 years (SD 12.3), and 342 patients were males. The primary tumors are listed in Table 1. The prevalence of mucositis was 22.3 %. The symptom relevantly reduced the ingestion of food or fluids and was statistically associated with the Karnofsky level and head and neck cancer. The prevalence of dry mouth was 40.4 %, with a mean intensity of 5.4 (SD 2.1). Several drugs were concomitantly given, particularly opioids (78 %), corticosteroids (75.3 %), and diuretics (70.2 %). Various and nonhomogeneous treatments were given for dry mouth, that was statistically associated with current or recent chemotherapy, and hematological tumors. The prevalence of dysphagia was 15.4 % with a mean intensity of 5.34 (SD 3). Dysphagia for liquids was observed in 52.4 % of cases. A high level of limitation for oral nutrition due to dysphagia was found, and in 53.4 % of patients, alternative routes to the oral one were used. Dysphagia was statistically associated with the Karnofsky level and head and neck cancer. A strong relationship between the three oral symptoms was found. CONCLUSION: In advanced cancer patients, a range of oral problems significantly may impact on the physical, social, and psychological well-being of advanced cancer patients to varying degrees. These symptoms should be carefully assessed early but become imperative in the palliative care setting when they produce relevant consequences that may be life-threatening other than limiting the daily activities, particularly eating and drinking.

Italian Oncological Pain Survey (IOPS): a multicentre Italian study of breakthrough pain performed in different settings.

OBJECTIVE: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). METHODS: A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. RESULTS: 1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. CONCLUSION: This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient's quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics.

The Liverpool Care Pathway for cancer patients dying in hospital medical wards: a before-after cluster phase II trial of outcomes reported by family members.

BACKGROUND: Hospital is the most common place of cancer death but concerns regarding the quality of end-of-life care remain. AIM: Preliminary assessment of the effectiveness of the Liverpool Care Pathway on the quality of end-of-life care provided to adult cancer patients during their last week of life in hospital. DESIGN: Uncontrolled before-after intervention cluster trial. SETTINGS/PARTICIPANTS: The trial was performed within four hospital wards participating in the pilot implementation of the Italian version of the Liverpool Care Pathway programme. All cancer patients who died in the hospital wards 2-4 months before and after the implementation of the Italian version of Liverpool Care Pathway were identified. A total of 2 months after the patient's death, bereaved family members were interviewed using the Toolkit After-Death Family Interview (seven 0-100 scales assessing the quality of end-of-life care) and the Italian version of the Views of Informal Carers - Evaluation of Services (VOICES) (three items assessing pain, breathlessness and nausea-vomiting). RESULTS: An interview was obtained for 79 family members, 46 (73.0%) before and 33 (68.8%) after implementation of the Italian version of Liverpool Care Pathway. Following Italian version of Liverpool Care Pathway implementation, there was a significant improvement in the mean scores of four Toolkit scales: respect, kindness and dignity (+16.8; 95% confidence interval = 3.6-30.0; p = 0.015); family emotional support (+20.9; 95% confidence interval = 9.6-32.3; p < 0.001); family self-efficacy (+14.3; 95% confidence interval = 0.3-28.2; p = 0.049) and coordination of care (+14.3; 95% confidence interval = 4.2-24.3; p = 0.007). No significant improvement in symptom' control was observed. CONCLUSIONS: These results provide the first robust data collected from family members of a preliminary clinically significant improvement, in some aspects, of quality of care after the implementation of the Italian version of Liverpool Care Pathway programme. The poor effect for symptom control suggests areas for further innovation and development.

Orphan symptoms in advanced cancer patients followed at home.

Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and deserve further analyses. Given the low prevalence of these symptoms, large studies are needed to find possible associated factors.

Opioid switching in patients with advanced cancer followed at home. A retrospective analysis.

CONTEXT: Opioid switching has been found to improve opioid responsiveness in different conditions. However, data on opioid switching performed at home are almost nonexistent, despite the fact that most patients are followed at home. OBJECTIVES: The aim of this retrospective survey was to determine frequency, indications, usefulness, and safety of opioid switching when treating advanced cancer-related pain in patients followed at home. METHODS: A retrospective review of data from patients with advanced cancer followed at home by three home care teams for a period of two years was performed. Patients who had their opioids switched were selected. Reasons for switching opioid doses and routes of administration and outcomes were collected. RESULTS: Two hundred one (17%) of 1141 patients receiving "strong" opioids were switched. The mean Karnofsky Performance Status score was 35.6, and the median survival was 30 days. The most frequent reason to switch was for convenience, and the most frequent switch was to parenteral morphine. In most patients, a better analgesic response was observed. Patients who were switched to parenteral morphine had a shorter survival in comparison with other opioid sequences (P<0.0005). After switching, opioid doses were increased by 23% and 41%, after a week and at time of death, respectively. CONCLUSION: Opioid switching was useful for most patients in the home environment, at least in less complex circumstances, when done by experienced home care teams. Prospective studies are needed to provide information about the decision to admit to hospital for this purpose and the predictive factors that may relatively contraindicate transportation to a facility in severely ill patients.

Palliative sedation in advanced cancer patients followed at home: a retrospective analysis.

CONTEXT: Data regarding palliative sedation at home in dying patients are lacking. OBJECTIVES: To describe the frequency, indication, and modality of palliative sedation (PS) in patients followed at home. METHODS: A retrospective analysis of home care cancer patients was performed. Patients who received PS before dying were selected and information about epidemiologic characteristics, indications, duration, drugs, and outcomes was collected. RESULTS: Of 370 medical charts of patients who died at home, 49 patients received PS before dying. PS was proposed by the team, relatives, or both in 63.3%, 4.1%, and 32.6% of cases, respectively. Delirium alone or in combination with other symptoms was the most frequent indication to begin PS. Midazolam was the most frequently used drug to initiate PS (98%), at a mean dose of 28.1 mg/day, in combination with parenteral morphine (84.7%) at a mean dose of 25.4 mg/day. At the time of death, midazolam was administered in 98% of patients (mean dose 22.3 mg/day), combined with parenteral morphine in 87.8% of patients (mean dose 28.1 mg/day). Satisfaction for physicians and principal caregivers after PS was good in 46 and 48 cases, respectively. CONCLUSION: PS at home seems to be a feasible treatment option among selected patients and makes a potentially important contribution to improving care for those who choose to die at home.

How do cancer patients receiving palliative care at home die? A descriptive study.

CONTEXT: Data regarding the circumstances of the process of death of terminally ill patients followed at home are lacking. OBJECTIVES: The aim of this study was to describe the characteristics and assess the circumstances of the process of death of terminally ill patients followed at home. METHODS: This was a prospective survey to assess the dying process of advanced cancer patients followed at home. Within a week after death, the principal caregiver was interviewed. Information from the palliative home care team and the caregiver about expectation of death, time of death, professional and nonprofessional people present at time of death, emergency admission to hospital, and administration of drugs to resuscitate was gathered. The principal clinical issues in the last two hours also were recorded. RESULTS: In total, 181 of 222 caregivers provided information. Most deaths were expected. Palliative home care team physicians and nurses visited the patient on the day of death but were occasionally present at the moment of death. More than three people were generally present at time of death. More than two-thirds of patients died peacefully, without apparent suffering, and 35.7% of them received palliative sedation before dying. In the last two hours, the most frequent clinical issues were ranked as death rattle, dyspnea, and agitation. In 10 cases, emergency drugs for resuscitation were administered. CONCLUSION: This study has shown how advanced cancer patients die at home and that palliative home care may be helpful in allowing a death at home, particularly when relatives are actively involved.

Palliative sedation in patients with advanced cancer followed at home: a systematic review.

CONTEXT: Patients with advanced cancer who are near the end of life may experience intolerable suffering refractory to targeted palliative therapies. Palliative sedation (PS) is considered to be an effective treatment modality for these refractory symptoms when aggressive efforts fail to provide relief. OBJECTIVES: The aim of this study was to systematically review articles regarding PS performed at home in patients with intractable symptoms. METHODS: Literature databases searched included MedLine, PubMed, and EMBASE. The text words and MeSH/EMTREE terms "home care" and "sedation" were used for electronic database searches. RESULTS: Six articles met the inclusion criteria for research and reported data regarding patients who were sedated at home. Although an early study reported a rate of more than 50%, the majority of the most recent literature, even though retrospective, shows an incidence of PS of 5%-36%. Agitated delirium, dyspnea, and pain were the most common problems requiring PS. The duration was variable (the mean across studies 1-3.5 days), and has not been statistically associated with hastened death. Benzodiazepines, specifically midazolam, have been most frequently used, alone or in combination with neuroleptics and opioids; in one article, opioids were given alone. CONCLUSION: PS at home seems to be a feasible treatment option among selected patients and makes a potentially important contribution to improving care for those who choose to die at home. Although the existing studies provide only low-quality evidence, the decision to use PS does not seem to anticipate patients' death. More homogeneous prospective studies on a large number of patients should confirm this observation.

Breakthrough pain in advanced cancer patients followed at home: a longitudinal study.

The aim of this study was to longitudinally assess breakthrough pain (BP) in advanced cancer patients who were admitted to home palliative care. One hundred and one consecutive patients who were admitted to one of the two home care programs and were representative of the cancer population followed at home in Italy were included. Patients were excluded only if at admission they were cognitively impaired or too unwell to provide reliable answers to questions regarding data collection. At admission (T(0)), and one month later (T(1)), data were recorded about the pharmacological treatment of background pain and its effectiveness; the presence of BP and its intensity, duration, and number of episodes; the occurrence of BP induced by movement; spontaneous relief after stopping activity and limitation of physical activity because of pain on movement; the analgesic drugs prescribed for BP; and the effectiveness of BP medication. After the initial assessment, patients received analgesics for background pain and BP, as well as symptomatic treatment usually provided at home, according to local policies and protocols. At T(0), 70.2% of patients were receiving analgesic drugs, and 52% of them had uncontrolled pain. BP was reported by 49.2% of these patients and had a mean duration and number of episodes per day of 35.1 minutes (+/-35.0) and 2.4 (+/-1.5), respectively. Of patients with BP, 65.7% had pain on movement, which decreased spontaneously after stopping activity in 73.9%. Physical activity was strongly limited in 78.2% of these patients. Most patients did not have a BP medication prescription. At T(1), a larger number of patients were receiving analgesics (P<0.002), and the number of patients with BP medication significantly increased (P<0.001). The incidence of BP and pain on movement decreased (33% and 38.5%, respectively). This longitudinal study suggests that BP is a dynamic entity dependent on several factors, including analgesic treatment and the course of disease. This helps explain the different incidences reported in previous studies performed in different settings and conditions.

Randomized double-blind, double-dummy crossover clinical trial of oral tramadol versus rectal tramadol administration in opioid-naive cancer patients with pain.

Tramadol is commonly used as second step drug of the analgesic ladder. In circumstances where the oral route is unavailable, rectal administration of opioids might be a simple alternative. The aim of this study was to compare the analgesic activity and tolerability of tramadol by oral and rectal administration in a double-blind, double-dummy crossover trial. The study included 60 cancer patients with cancer pain no longer responsive to non-opioid drugs. Each patient initially received oral tramadol 50 mg (drops), followed by tramadol sustained release 100 mg orally, and placebo rectally, or tramadol 100 mg rectally and placebo orally, twice a day, in a randomized sequence, on each of 3 days. Patients were allowed to take 50 mg of oral tramadol by drops as needed (four doses per day, to a maximum of 400 mg/day, including the basal dose given by the oral or rectal route). Pain intensity and relief and symptom scores were recorded every day and at the end of each phase of the crossover. The mean age of the patients was 66.1 years (SD 13.5 years); 36 were female, and 44 completed both periods. Patients dropped out due to adverse effects (15 patients) and refusal (1 patient). No differences in the use of rescue dose of oral tramadol were observed between the groups. No differences in pain intensity and relief scores, or in other symptoms between the two treatments were observed. No differences in treatment efficacy as judged by the clinician (P=0.73), in patient compliance (P=0.35), or in patient satisfaction regarding treatment (P<0.35) were found. No differences in adverse effects were found between the two treatments (25.5%, 13 patients, and 20.4%, 11 patients, with oral and rectal treatment, respectively). The proportion of preferences favored oral administration for both physicians (P=0.0002) and patients (P=0.002). Rectal administration of tramadol appears a reliable, noninvasive alternative method of pain control for patients no longer responsive to non-opioid analgesics, unable to take oral tramadol.

Factors involved in gastrointestinal bleeding in advanced cancer patients followed at home.

There is a lack of information on the frequency of symptomatic gastrointestinal bleeding in patients with advanced cancer. This group of patients presents several risk factors for developing gastrointestinal bleeding. The aim of this multicenter longitudinal survey was to assess the frequency of gastrointestinal bleeding and possible factors implicated in advanced cancer patients followed at home. A consecutive sample of 439 patients who referred to home palliative care program entered the study. Age, gender, primary cancer and known metastases, possible associated pathologies, history of peptic disease, use of previous or actual nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids, drugs used to prevent gastric complications, the occurrence of hematemesis or melena, significant anemia requiring blood transfusion, and mortality associated with the hemorrhagic event were recorded. Of 377 patients who completed the study, 18 reported gastrointestinal bleeding, and five had significant anemia requiring blood transfusion in three cases. Death was found to be related to bleeding in three patients. NSAIDs, steroids, and gastroprotectors were frequently used, either before or during home care. However, no clear relationship between age, gender, and the use of offender drugs with gastrointestinal bleeding was found. Liver involvement was frequently associated with the risk of developing gastrointestinal bleeding.

Respiratory problems in advanced cancer.

Respiratory problems are an important issue in the palliative care setting, not only from a diagnostic and therapeutic point of view but also from emotion-related aspects involving both the patients and their families and also caregivers. In this paper we consider some of the most common respiratory problems, such as dyspnea, infections, hemoptysis, hiccup. A review of the literature was performed with reference to the frequency, diagnosis and management of the above respiratory problems in patients in advanced and terminal stages of the disease. Particular emphasis was given to the importance of communication with the patients and their families, which is considered a crucial point in the care and the cure of such patients.