***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Objectives To evaluate whether the current European Association for Palliative Care recommendation regarding the starting dose of 5 mg of normal-release morphine ( NRM ) sulfate oral solution every 4 hours in opioid naive patients or 10 mg in patients already being treated with “ weak ” opioids is effective and could be proposed as starting routine dose in clinical practice . Secondary aims were to estimate the percentage of patients who were high responders to NRM and to study the association of baseline patient characteristics with both high analgesic responsivity and the need of opioid dose escalation . Methods Consecutive strong opioid-naive patients with cancer pain were enrolled in a multicenter uncontrolled phase 4 clinical trial .  Oral NRM was administered at 2 different dosages : 5 and 10 mg every 4 hours , respectively , for opioids-naive ( group A ) and nonopioids-naive ( group B ) patients as starting therapy . Average daily dosages of NRM and opioid escalation index ( OEI ) were calculated and the reduction in pain score was tested through Student t test both in group A and in group B patients . Results One hundred fifty-nine consecutive patients were enrolled and data analysis was conducted on 151 ( 95 % ) patients . On an average the OEIs were : 3.2 in group A and 6.5 in group B and a significant reduction in pain score both after 3 and 5 days from baseline ( P<0.001 ) was shown in both groups . In multivariate analysis both Karnofsky Performance Status and episodic pain showed to be independent prognostic factors of a high analgesic response . The presence of neuropathic pain showed to be associated with a higher OEI . Discussion These data show that empiric st and ard doses of NRM during titration , recommended by European Association for Palliative Care , are effective in clinical practice To treat cancer pain , physicians often decide to jump directly from step 1 of the World Health Organization ( WHO ) analgesic ladder to step 3 . The use of transdermal fentanyl in patients with cancer pain who had either used no opioid before , or only codeine  , is evaluated in the present trial . Both opioid-naive ( N = 14 ) and codeine-using ( N = 14 ) patients started with transdermal fentanyl in the lowest available delivery rate ( 25 microg/hr ) . Immediate-release oral morphine was present as " rescue " medication . Transdermal fentanyl provided good to excellent pain relief in the majority ( 68 % ) of these patients . During the study , 5 patients continued with 25 microg/hr , and the others used a higher dose . Clinical ly relevant respiratory depression was not observed . The common side effects of opioids were found ; constipation was mentioned by 3 patients ( 11 % ) . Transdermal fentanyl appeared a safe analgesic in these opioid-naive cancer pain patients . In this study , WHO step 2 could be skipped without untoward complications BACKGROUND In a multicenter study , 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization ( WHO ) were switched to oral slow-release morphine . METHODS Patients received intravenous morphine through a patient-controlled pump ( PCA ) for the first 24 hours ( bolus = 1 mg , lockout interval = 5 minutes , maximum dose = 12 mg/hour ) . From day 2 patients were treated with oral slow-release morphine . Daily doses were calculated from the requirements of the day before . Breakthrough pain was treated with PCA until stable doses were reached ( < 2 boluses/day ) and then with oral immediate-release morphine solution .  Pain intensity was reported in a diary four times a day , in addition to mood , activity , and quality of sleep once daily . RESULTS Mean duration until adequate pain relief reported ( < 30 on a 101-step numerical scale ; NRS ) was 5 hours ( range = 80 - 620 minutes ) . Mean pain intensity was reduced from 67 NRS to 22 NRS . Mean doses of oral morphine  were 133 mg/day initially and then 154 mg/day on day 14 . Serious adverse events such as respiratory depression were not observed . Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction . Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good . CONCLUSIONS Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain . Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration & NA ; A titration procedure using immediate‐release morphine given 4‐hourly is recommended during start of oral morphine for cancer pain . This recommendation is not based on evidence from controlled studies , and many physicians start morphine treatment with controlled‐release morphine . We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a r and omized , double‐blind , double‐dummy , parallel‐group study comparing titration with immediate‐release morphine given 4‐hourly with titration with sustained‐release morphine given once daily . The primary end point was the time needed to achieve adequate pain relief Secondary end points were other symptoms ( nausea , tiredness , lack of sleep , vertigo , appetite and constipation ) , health related quality of life and patient satisfaction . The mean times needed for titration were 2.1 ( 95 % CI ; 1.4–2.7 ) days using immediate‐release morphine and 1.7 ( 95 % CI ; 1.1–2.3 ) days using sustained‐release morphine . Patients titrated with immediate‐release reported statistically significant more tiredness at the end of titration . We observed no other differences in adverse effects or health related quality of life functions between the two treatments . Similar global satisfactions with the morphine treatments were reported . In conclusion , a simplified titration using sustained‐release morphine once daily is equally effective as immediate‐release morphine given 4‐hourly SUMMARY Objective : To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids , weak opioids or non-opioid analgesia .  Methods : Cancer patients requiring strong analgesia were recruited into an open-label , multicentre study , conducted in eight countries . Patients received transdermal fentanyl treatment for 28days . Pain severity , overall satisfaction with pain control , convenience of use of patches and treatment preferences were recorded daily . Results : Of the 292 participants , 135 had previously received a strong opioid , 84 had previously received a weak opioid and 73 had received no regular opioids . Thirty-eight patients did not complete the study , mainly due to adverse events .  For all groups the proportion of patients with ‘ good to excellent ’ pain control increased after transdermal fentanyl treatment . Transdermal fentanyl was well tolerated , with the most common treatment-related adverse events being nausea , vomiting and constipation . The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups . Most patients rated the convenience of the patches as ‘ good to excellent ’ , and most preferred transdermal fentanyl to their previous therapy . Conclusions : Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids . Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary , and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief BACKGROUND Considerable dose variations and frequent initial side effects have been postulated during start of morphine treatment to patients with pain caused by malignant disease . However , to our knowledge , only one previous study has reported effective doses in  morphine naive cancer patients and no prospect i ve evaluation has compared symptoms before with symptoms during morphine titration . METHODS We recruited 40 cancer patients with uncontrolled pain despite receiving codeine or dextropropoxyphen .  Baseline data were obtained for two days before start of morphine titration using a fixed scheduled escalation of immediate-release ( IR ) morphine . When a stable morphine dose was achieved , IR morphine was replaced with slow-release ( SR ) morphine in equivalent doses . Intensity of pain and side effects were assessed daily . The daily consumption of morphine , rescue analgesics and rescue antiemetics were registered . RESULTS The mean titration time to achieve adequate analgesia was 2.3 days ( range : 1 - 6 ) using a mean daily morphine dose of 97 mg ( range : 60 - 180 ) . Nausea was unaltered after start with morphine but an increased incidence of vomiting occurred ( premorphine period 5 % , IR morphine period 29 % ) . Transient sedation delayed dose increment in 9 of the 40 patients but mean sedation scores were unaltered . Constipation scores increased while other side effect scores were unaltered . Eighty-two percent of the patients were satisfied or very satisfied with the pain treatment during introduction of morphine . CONCLUSION In cancer patients with uncontrolled pain on weak opioids , successful titration of morphine is achieved fast , with a three-fold morphine dose variation and with little increase in side effects This report is a prospect i ve study of 223 patients with intractable cancer pain who were offered continuing care during the year 1988 at the Pain Relief Unit , Kidwai Memorial Institute of Oncology , Bangalore , India , with a minimum follow‐up of 4 months and a maximum follow‐up of 16 months . A high percentage of pain relief was attained within a mean duration of 4 days , which on follow‐up was maintained at a steady level in most patients ( 91.1 % ) . Oral morphine could not be continued in three patients because of vomiting . The main side effects noticed were nausea and vomiting , itching , and constipation . At any time during the first 140 days , only 30 % of patients had side effects and appropriate medication successfully managed these side effects . During the rest of the study period , the side effects were minimal . Oral morphine used with proper adjuncts offers the best pain palliation in most patients , with minimal side effects Initial dose finding in patients with cancer pain who are started on TTS fentanyl ( Duragesic , TTS-F ) is often unsatisfactory with currently recommended doses and intervals . Acknowledging that studies reveal a " psuedo steady state " 15 to 20 hr after application of TTS-F , we prospect ively investigated an increased initial dose and day-to-day titration of TTS-F in 39 ( evaluable ) patients with uncontrolled cancer pain . Significant pain reduction ( P = 0.001 ) was seen after 24 hr , and satisfactory analgesia was achieved within 48 h and maintained for the rest of the study . Significant increases in  TTS-F  were necessary during weeks 1 through 4 to maintain pain control . Forty-nine percent of the patients needed one or more early dose increases . Only one patient had side effects partially due to the specific properties of the TTS . Other side effects seemed to be less common compared with usual morphine treatment . TTS-F can be titrated effectively and safely on a day-to-day basis with an increased initial dose and adequate patient monitoring , thus avoiding more complicated approaches . TTS-F seemed to induce less constipation than might be expected This r and omized controlled trial compared intravenous route with oral route for initial dose titration of morphine in 62 patients with end-stage cancer and severe pain . Patients in the intravenous group received 1.5 mg intravenous bolus doses of morphine every ten minutes till pain relief was total or until they became drowsy . After that they got oral morphine at a dose equal to the total initial intravenous requirement four-hourly . Patients in the oral group got oral morphine 5 mg doses ( if opioid-naÖve ) or 10 mg ( if already on weak opioid ) four hourly . Patients in both groups had the option to receive rescue doses of their regular oral dose as and when needed , if necessary hourly . Twenty-seven of 31 in the intravenous group had either total or satisfactory pain relief by the end of one hour , whereas only eight of 31 in the oral group had a similar result . After 24 hours and later both groups had similar results . There was no immediate serious side effect in any of the patients . The late side effects were similar in the two groups . In the intravenous group , the ratio of initial intravenous dose requirement to the subsequent regular single oral dose after two days centred around 1:1 ( range 1:0.5 - 1:3.3 ) . This study found the intravenous method to be safe , effective and superior to the traditional method in providing immediate relief to severe cancer pain Abstract Objective : Moderate to severe pain is commonly experienced by cancer and non-cancer patients . Although opioids are generally the most important drugs in chronic pain management , their use in Italy remains low . We design ed a prospect i ve open trial to assess the efficacy and safety of a st and ard therapy clinical ly available for a large range of patients . Methods : A total of 172 consecutive patients ( 89 women and 83 men ) with chronic pain ( daily mean visual analogue scale ( VAS ) score > 4 ) that was not adequately managed by their existing pain regimen were enrolled to receive an immediate release ( IR ) dose of morphine : 30 mg/day ( opioid-naive patients ) or 60 mg/day ( non-naive patients ) for 5 days . After this period ( start therapy ) , all patients were switched to slow release ( SR ) opioid therapy for 30 days ( steady therapy ) . Each breakthrough pain ( BTP ) episode 
    Output:
    
All treatment strategies result ed in acceptable pain control and were well tolerated .