Multinational evaluation of clinical decision-making in the treatment and management of mild-to-moderate ulcerative colitis.

OBJECTIVES: To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). METHODS: This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios - active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. RESULTS: A total of 157 individual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52; 93% specialist gastroenterologists) from Europe and North America (25; 45%), South America (19; 34%) and the Middle East, Asia and Australia (12; 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. CONCLUSION: The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history.

Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).

AIM: We characterised the distress that parents experienced when their child was hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This survey-based, observational study was conducted during 2014-2015. Meetings were held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11 healthcare professionals experienced in RSV, which identified 110 factors related to parental distress. The resulting questionnaire was completed by another 105 Spanish and Italian parents and 56 healthcare professionals, to assess the impact these factors had on parental distress, using a scale from 0 to 10 (very unimportant to very important). RESULTS: The five most important factors for parents were: healthcare professionals' awareness of the latest developments, readmission, reinfections, painful procedures and positive experiences with healthcare professionals. Healthcare professionals associated only medical factors with a meaningful impact on parents. Half of the six medical factors were given similar importance by both groups and the overall scoring for the 110 factors was comparable, with a correlation coefficient of 0.80. A primary concern on discharge was ongoing support. CONCLUSION: The relationship between parents and healthcare professionals was a significant factor in determining parental distress. Healthcare professionals appeared to have a good understanding of the overall impact on parents, particularly the key medical factors.

Efficacy of oral prolonged-release mesalazine in moderately active ulcerative colitis.

New meta-analyses are presented that provide further evidence supporting the effectiveness of oral prolonged-release mesalazine compared to other oral mesalazines as induction therapy in patients with moderately active ulcerative colitis.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.

BACKGROUND AND OBJECTIVE: To assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST). METHODS: A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included. RESULTS: Cost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231). CONCLUSIONS: Palivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

The evolution of risk factors for respiratory syncytial virus-related hospitalisation in infants born at 32-35 weeks' gestational age: time-based analysis using data from the FLIP-2 study.

AIM: The aim of this study was to examine whether the risk for respiratory syncytial virus (RSV)-related hospitalisation changes through the first year of life in infants of 32-35 weeks' gestational age (wGA). METHODS: Risk factors from the FLIP-2 study (190 cases/4566 age-matched controls) were included in a Cox regression analysis wherein time slices were taken at 1-month intervals from birth. RESULTS: Half of all RSV hospitalisations occurred in the first 68 days after birth, with 56% occurring within 90 days. The time taken for 50% of hospitalisations to occur was 148 days for those born outside the RSV season and 58 days for those born within the season. By 90 days old, 84% of infants born in the season and 20% of those born outside the season were hospitalised. In both groups, hospitalisations occurred ≥5 months after birth. Male sex, smoking whilst pregnant, month of birth, duration of breastfeeding, number of siblings at school, and number of smokers in household all contributed to the risk of RSV hospitalisation beyond the age of 90 days. CONCLUSIONS: The risk of RSV hospitalisation appears to persist to at least 5-6 months old in 32-35 wGA infants, which has implications for the optimal management of disease prevention.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission. METHODS: Literature searches were conducted in PubMed, Embase and Cochrane databases, from inception to 02 December 2020. Unpublished studies were also sourced. Meta-analyses using a random-effects model and Bayesian inference compared Pentasa (tablets, granules, capsules) against placebo and other 5-ASAs. RESULTS: Twelve studies involving 3674 patients treated with Pentasa were identified. Pentasa 2-4 g/day was superior to placebo at inducing (absolute risk difference [ARD] at 8 weeks 0.14, 95% CI 0.07‒0.21; p < .001) and maintaining (ARD 6-12 months 0.18, 95% CI 0.04‒0.33; p < .05) remission (clinical/endoscopic). Against other 5-ASAs, Pentasa had similar efficacy for induction (ARD <0.001, 95% CI -0.05‒0.05) and maintenance (ARD 0.01, 95% CI -0.07‒0.08) treatment using randomized controlled trial data. Upon inclusion of real-world study data, Pentasa was significantly better at maintaining remission compared both to Eudragit-S mesalazine and sulfasalazine (ARD 0.04, 95% CI 0.02‒0.06; p < .001). Pentasa (1-4 g/day) had similar treatment-related adverse event rates to placebo (ARD 0.02, 95% CI -0.03‒0.06) and Eudragit-L/S mesalazines (2.25-3 vs 2.4-3 g/day, respectively; ARD -0.03, 95% CI -0.12‒0.05), but was better tolerated than sulfasalazine (3 g/day) (ARD 0.07, 95% CI 0.003‒0.14; p < .05). CONCLUSION: This study confirms oral Pentasa is efficacious and well-tolerated in treating active UC and maintaining remission. The availability of multiple forms of Pentasa supports physicians' ability to individualize treatment and optimize dosing to improve outcomes.

Adoption in Canada of an international risk scoring tool to predict respiratory syncytial virus hospitalization in moderate-to-late preterm infants.

OBJECTIVE: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST. METHODS: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed. RESULTS: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores (p < .001) and risk categories (p < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%). CONCLUSIONS: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Validation of a model to predict hospitalization due to RSV of infants born at 33-35 weeks' gestation.

BACKGROUND: A model to predict hospitalization due to respiratory syncytial virus (RSV) of infants born at 33- 35 weeks' gestation was developed using seven risk factors from the Spanish FLIP study "birth +/-10 weeks from the beginning of the RSV season", "birth weight", "breast fed or=2 years", "number of family members with atopy", "number of family members with wheezing", and "gender". The aim of this study was to validate the model using French data. METHODS: The FLIP model [predictive accuracy 71%, receiver operating characteristic (ROC) 0.791] was tested against the French data (77 hospitalized infants with RSV born at 33-35 weeks and 154 age-matched controls) using discriminatory function analysis by applying the FLIP coefficients to the French data and by generating the seven variable model from the French data. RESULTS: Applying the FLIP coefficients to the French dataset, the model correctly classified 69% of cases (ROC 0.627). The predictive power increased to 73% (ROC 0.654) when "number of siblings >or=2 years" was substituted for "number of children at school". The number needed to treat (NNT) in order to prevent 70% of hospitalizations was 18. The model derived using French data could correctly classify 62% of cases in the French data (ROC 0.658). CONCLUSIONS: The model was successfully validated and may potentially optimize immunoprophylaxis in French infants born at 33-35 week's gestation.

The use of 5-aminosalicylates in Crohn's disease: a retrospective study using the UK Clinical Practice Research Datalink.

BACKGROUND: There are few recent studies on the use of 5-aminosalicylates (5-ASA) as therapy for Crohn's disease (CD) in routine clinical practice. The aim of this database investigation was to provide real-world evidence on 5-ASA use in CD. METHODS: Patients with CD, aged ≥18 years when first prescribed 5-ASA (index date) and having received 5-ASA at any time between 01 January 2006 and 07 May 2018, were included for analysis. Outcomes included treatment patterns and resource use. RESULTS: Of 21,456 patients with CD, 9492 (44.2%) had been prescribed 5-ASA, with the majority (5606; 59.1%) starting on oral 5-ASA as monotherapy. 58.3% (5537) of patients on 5-ASA did not require dose change, 67.6% (6416) did not require supplementary treatment (e.g., corticosteroids, immunosuppressants, etc.), and 4.6% (436) required a switch to another treatment. Resource use was significantly decreased in the year after vs. year before 5-ASA initiation (including: specialist referrals, hospitalizations and hospital days; all P<0.001). Patients remained on 5-ASA for a median of 4.7 years (interquartile range 1.2-10.1). 25.3% (2406) of patients were still on 5-ASA at 10 years. There was a significant correlation between earlier use of 5-ASA following diagnosis and longer 5-ASA retention (P<0.001). CONCLUSIONS: 5-ASA is widely used as a long-term treatment for CD, as evidenced by continuation rates extending beyond 10 years in a quarter of patients. CD-related healthcare resource use decreased significantly in the year following 5-ASA initiation. Earlier use was associated with longer retention.

A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33-35 weeks of gestational age, based on data from the Spanish FLIP Study.

BACKGROUND: The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33-35 weeks' gestational age (GA). METHODS: The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33-35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted. RESULTS: An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth +/- 10 weeks of start of season, birth weight, breast feeding for < or = 2 months, siblings > or = 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768-0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5-13.6). CONCLUSION: A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33-35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe.

IBD2020 global forum: results of an international patient survey on quality of care.

BACKGROUND/AIMS: IBD2020 is a global forum for standards of care in inflammatory bowel disease (IBD). The aim of the IBD2020 survey was to identify and describe variations in quality care of IBD. METHODS: Patients with IBD from Finland, Italy, France, Canada, Germany, UK, Spain and Sweden were surveyed during 2013 to 2014, covering: disease characteristics; impact on life and work; organization and perceived quality of care. RESULTS: Seven thousand five hundred and seven patients participated (median age, 39 years [range, 10-103 years]; 2,354 male [31.4%]), including 4,097 (54.6%) with Crohn's disease (CD) and 3,410 (45.4%) with ulcerative colitis (UC). Median time from symptom onset to diagnosis was 1 year for both CD (range, 0-47 years) and UC (range, 0-46 years), with no clear evidence of improvement in diagnostic delay over the preceding 24 years. Half of the patients (3,429; 50.0%) rated their care as "excellent" or "very good," with similar results for CD and UC across countries. Five factors were significantly (P<0.01) associated with perceived good quality of care: quality of specialist communication; review consultation being long enough; failure to share information; no access to a dietician; speed of advice. CONCLUSIONS: The IBD2020 survey has highlighted areas related to quality of care of IBD from the patients' perspective, with scope for improvement.

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants.

BACKGROUND: The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere. METHODS: Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated. RESULTS: The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3). CONCLUSIONS: This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.

The influence of birth weight amongst 33-35 weeks gestational age (wGA) infants on the risk of respiratory syncytial virus (RSV) hospitalisation: a pooled analysis.

OBJECTIVE: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33°-356 weeks' gestational age (wGA) infants. STUDY DESIGN: Pooled analysis of data (n = 1218) from Spain, Germany, France and Italy. RESULT: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14 kg; p < 0.001) for both males (2.25 versus 2.18 kg; p = 0.049) and females (2.22 versus 2.11 kg, p = 0.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95 kg versus non-hospitalised 1.95 kg, p = 0.976; 34 wGA: 2.26 versus 2.14 kg, p = 0.007; 35 wGA: 2.37 versus 2.29 kg, p = 0.070), particularly female 34 wGA infants (female: 2.24 versus 2.08 kg, p = 0.019; male: 2.27 versus 2.20, p = 0.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation. CONCLUSIONS: In 33-35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation.

Can we improve the targeting of respiratory syncytial virus (RSV) prophylaxis in infants born 32-35 weeks' gestational age with more informed use of risk factors?

OBJECTIVE: To evaluate the key risk factors for respiratory syncytial virus (RSV) hospitalisation in 32-35 weeks' gestational age (wGA) infants. METHODS: Published risk factors were assessed for predictive accuracy (area under the receiver operating characteristic curve [ROC AUC]) and for number needed to treat (NNT). RESULTS: Key risk factors included: proximity of birth to the RSV season; having siblings; crowding at home; day care; smoking; breast feeding; small for GA; male gender; and familial wheezing/eczema. Proximity of birth to the RSV season appeared the most predictive. Risk factors models from Europe and Canada were found to have a high level of predictive accuracy (ROC AUC both > 0.75; NNT for European model 9.5). A model optimised for three risk factors (birth ± 10 weeks from start of RSV season, number of siblings ≥ 2 years and breast feeding for ≤ 2 months) had a similar level of prediction (ROC AUC: 0.776; NNT: 10.2). An example two-risk factor model (day care attendance and living with ≥ 2 siblings < 5 years old) had a lower level of predictive accuracy (ROC AUC: 0.55; NNT: 26). CONCLUSIONS: An optimised combination of risk factors has the potential to improve the identification of 32-35 wGA infants at heightened risk of RSV hospitalisation.

Comparative efficacy of bisphosphonates in metastatic breast and prostate cancer and multiple myeloma: a mixed-treatment meta-analysis.

PURPOSE: A mixed-treatment comparison (MTC) was undertaken to compare the efficacy of zoledronic acid, clodronate, pamidronate, and ibandronate (i.v. and oral) in patients with skeletal-related events (SRE) secondary to metastatic breast and prostate cancer and multiple myeloma. EXPERIMENTAL DESIGN: Studies of bisphosphonates in the three malignancies were identified and SRE data were extracted. Outcomes from the MTC were expressed as the annual SRE rate and as the mean likelihood (probability) ratio for the rate of SREs during treatment with zoledronic acid compared with the other bisphosphonates. RESULTS: A total of 17 studies were identified (7 breast, 3 prostate, and 7 multiple myeloma). Data were available for all bisphosphonates in breast cancer; no data were available for ibandronate (oral or i.v.) in prostate cancer or for oral ibandronate in multiple myeloma. The SRE rates in breast cancer were 1.60 for zoledronic acid, 1.67 for oral ibandronate (excess SRE rate, 4%), 1.70 for i.v. ibandronate (6%), 2.07 for pamidronate (29%), and 2.29 for clodronate (42%). In prostate cancer, the SRE rates were 0.83 for zoledronic acid, 1.11 for clodronate (35%), and 1.41 for pamidronate (71%). In multiple myeloma, the SRE rates were 1.43 for zoledronic acid, 1.64 for pamidronate (15%), 1.90 for clodronate (33%), and 2.49 for i.v. ibandronate (75%). CONCLUSIONS: Zoledronic acid seems to be the most efficacious bisphosphonate for reducing the risk of SREs in patients with cancer of the breast or prostate and those with multiple myeloma.

Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials.

CONTEXT: Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray. OBJECTIVES: To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator. METHODS: Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP. RESULTS: Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability). CONCLUSION: This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP.

Effects of parental and household smoking on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm infants and the potential impact of RSV prophylaxis.

OBJECTIVE: To assess the impact of household smoking and palivizumab prophylaxis on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm (32-35 weeks' gestational age) infants. METHODS: Familial smoking and other RSV risk factor data from the FLIP, FLIP-2 and IMpact studies and datasets from France, Germany and Italy, together with palivizumab prophylaxis data from the FLIP-2 and IMpact studies, were analysed using cross-correlation and Bayesian meta-analytical modelling employing Markov Chain Monte Carlo sampling. RESULTS: There were 2.35 times (95% confidence interval [CI] 1.37-4.02) as many hospitalisations amongst infants from smoking compared with those from non-smoking families. Among non-prophylaxed infants, there were 2.53 times (95% CI 1.27-4.94) as many RSV hospitalisations from smoking than from non-smoking families and that excess hospitalisation was reduced to 1.03 times (95% CI 0.38-2.99) amongst prophylaxed infants. Familial smoking correlates significantly (p < 0.01) with other RSV risk factors: positive correlation with number of school-age siblings, history of family atopy, family wheeze and gestational age; negative correlation with birth weight and breast feeding. CONCLUSIONS: Late-preterm infants from smoking families appear to be at heightened risk for severe RSV infection requiring hospitalisation of which the risk may be reduced with RSV prophylaxis.