Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program.

SOLAR-1 and BYLieve trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP) opened to PIK3CA-mutant HR+/HER2- ABC patients treated with alpelisib and fulvestrant. Primary endpoint was PFS by local investigators using RECIST1.1. Eleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1-16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95% CI: 4.7-6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95% CI: 37.8-52.8). In multivariable analysis, characteristics significantly associated with a shorter PFS were age < 60 years (HR = 1.5, 95% CI = 1.1-2.1), >5 lines of prior treatments (HR = 1.4, 95% CI = 1.0-2.0) and the C420R PI3KCA mutation (HR = 4.1, 95% CI = 1.3-13.6). N = 91 (39.1%) patients discontinued alpelisib due to adverse events. To our knowledge, this is the largest real-life assessment of alpelisib efficacy. Despite heavy pre-treatments, patients derived a clinically relevant benefit from alpelisib and fulvestrant.

Volume and rate of volcanic CO2 emissions governed the severity of past environmental crises.

The emplacement of large igneous provinces (LIPs) has been linked to catastrophic mass extinctions in Earth's history, but some LIPs are only associated with less severe oceanic anoxic events, and others have negligible environmental effects. Although it is widely accepted that massive magma outpouring can affect the environment through volatile degassing, it remains debated what controls the severity of environmental crises. Here, we demonstrate that the second-most-voluminous Phanerozoic LIP, the Kerguelen LIP, may have contributed to the early Aptian oceanic anoxic event 1a, a global event previously believed to have been caused by the Ontong Java LIP. Geochronological data show that the earliest eruptions of the Kerguelen LIP preceded the onset of oceanic anoxic event 1a by at least ∼5 million years. Analyses of CO2 abundances in melt inclusions combined with Monte Carlo simulations reveal that the volume and degassing rate of CO2 emissions from the Kerguelen LIP are an order of magnitude lower compared to LIPs that caused severe mass extinctions. We propose that the severity of volcanism-related environmental and biotic perturbations is positively correlated with the volume and rate of CO2 emissions. Our results highlight the significant importance of reducing and slowing down CO2 emission in preventing future disastrous environmental consequences.

Sputum exosomes: promising biomarkers for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology which leads rapidly to death. As diagnosis of IPF is complex, we aimed to characterise microRNA (miRNA) content of exosomes from sputum of patients with IPF. Using miRNA quantitative PCR array, we found a substantial dysregulation of sputum exosomal miRNA levels between patients with IPF and healthy subjects and identified a unique signature of three miRNAs. Interestingly, we found a negative correlation between miR-142-3p and diffusing capacity of the lungs for carbon monoxide/alveolar volume. This is the first characterisation of miRNA content of sputum-derived exosomes in IPF that identified promising biomarkers for diagnosis and disease severity.

[Child sexual abuse: Description of a French population having consulted in a forensic medical service between 2011 and 2015]. / Agressions sexuelles sur mineurs : étude d'une population d'enfants ayant consulté dans une unité médico-judiciaire hospitalière entre 2011 et 2015.

BACKGROUND: When child sexual abuse (CSA) is suspected, the detection of anogenital anomalies is rare. In France, since 2011, most clinical examinations of children for whom CSA is suspected take place in the forensic medical service (FMS). OBJECTIVES: To describe a population of children examined for suspected CSA in the FMS of the Nancy Regional University Hospital Center. PATIENTS AND METHODS: Children under the age of 18 who consulted for suspected CSA in the Nancy FMS between 2011 and 2015 were included. Demographic data as well as data from questioning, the physical examination, any further examination, and the medical conclusions were collected. RESULTS: Three hundred and twenty-five girls and 79 boys were enrolled. The average age at the time the abuse was committed was 118.9 months. Two hundred sixty-nine (66.6%) children alleged fondling and 59 (14.6%) fellatio. Two hundred twelve victims (52.5%) described a penetration, 163 (76.9%) in the vagina and 73 (34.4%) in the anus. Significant bruises were found at the examination of 13 children, accounting for 2.5% of all victims. Thirty-four (11.7%) girls had lesions in the external genitalia and 28 (9.8%) lesions of the virginal membrane. One boy (1.3%) had a nonspecific lesion of the external genitalia. Six (8.2%) children alleging anal penetrations showed injury. The examiner concluded that clinical examinations were compatible with alleged facts for 253 (62.6%) victims. It was impossible to conclude for 116 (28.7%) children. CONCLUSION: In the case of suspected CSA, the clinical examination is frequently normal. This examination must be performed by physicians trained in child abuse, under appropriate conditions. It is important not to jump to conclusions about the reality of the alleged facts. A multidisciplinary approach, with the cooperation of the medical, social, and forensics sector is necessary.

Effectiveness of inhaled corticosteroids in real life on clinical outcomes, sputum cells and systemic inflammation in asthmatics: a retrospective cohort study in a secondary care centre.

OBJECTIVES: The impact of inhaled corticosteroids (ICS) on eosinophilic inflammation in asthma is well established, but their effect in a real-life setting has not been extensively studied. Our purpose was to investigate the effect of ICS on airway and systemic inflammation as well as on clinical outcomes in patients with asthma from clinical practice. DESIGN, SETTING AND PARTICIPANTS: We conducted a retrospective analysis on asthmatics from a secondary care centre in whom ICS were initiated/increased (n=101), stopped/decreased (n=60) or remained stable (n=63, used as a control group) between two visits with available sputum and blood cell counts. RESULTS: The median time between both visits ranged from 1 to 2 years. Initiating or increasing ICS (median variation (IQR): 800 (400-1200) µg beclomethasone equivalent dose per day) reduced sputum eosinophils and fractional exhaled nitric oxide (P<0.0001) and to a lesser extent blood eosinophils (P<0.0001), while withdrawing or decreasing ICS (median variation (IQR): 900 (500-1200) µg beclomethasone equivalentdose per day) resulted in increased sputum eosinophils (P=0.008). No change was found in patients with a stable dose. The effectiveness of ICS in improving asthma control, quality of life, forced expiratory volume in 1 s (FEV1), bronchial hyper-responsiveness and exacerbation rate was only observed in the eosinophilic phenotype (sputum eosinophils ≥3%, n=79). In non-eosinophilic asthmatics, stepping-down ICS resulted in an improvement in asthma control and quality of life, without any significant change in FEV1 (n=38). CONCLUSIONS: Our results confirm the effectiveness of ICS on eosinophilic inflammation in real life and demonstrate that their clinical benefit seems to be restricted to eosinophilic asthmatics. Our data also support a try for stepping-down ICS in non-eosinophilic asthmatics.

Is it possible to claim or refute sputum eosinophils ≥ 3% in asthmatics with sufficient accuracy using biomarkers?

The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or <3% in 58% of our population.

Asthma Control and Sputum Eosinophils: A Longitudinal Study in Daily Practice.

BACKGROUND: Longitudinal trials have suggested that asthma control may be influenced by fluctuations in eosinophilic inflammation. This association has however never been confirmed in daily practice. OBJECTIVE: To investigate the relationship between asthma control and sputum eosinophils in clinical practice. METHODS: A retrospective longitudinal study was conducted on 187 patients with asthma with at least 2 successful sputum inductions at our Asthma Clinic. Linear mixed models were used to assess the relationship between asthma control and individual changes in sputum eosinophils. Receiver-operating characteristic curves were constructed to define minimal important differences (MIDs) of sputum eosinophils associated with a change of at least 0.5 in Asthma Control Questionnaire (ACQ) score. Then, a validation cohort of 79 patients with asthma was recruited to reassess this relationship and the accuracy of the MID values. RESULTS: A multivariate analysis showed that asthma control was independently associated with individual fluctuations in sputum eosinophil count (P < .001). In patients with intermittent/persistently eosinophilic asthma, we calculated a minimal important decrease of 4.3% in the percentage of sputum eosinophils (area under the curve [AUC], 0.69; P < .001) or 3.4-fold (AUC, 0.65; P = .003) for a significant improvement in asthma control and a minimal important increase of 3.5% (AUC, 0.67; P = .004) or 1.8-fold (AUC, 0.63; P = .02) for a significant worsening in asthma control. The association between asthma control and sputum eosinophils and the accuracy of the MIDs of sputum eosinophils were confirmed in the validation cohort. CONCLUSIONS: At the individual level, asthma control was associated with fluctuations in sputum eosinophil count over time.

An evaluation of the intensive care unit resources and utilization in Trinidad.

OBJECTIVES: To evaluate resources and utilization of Intensive Care Units in Trinidad and Tobago. DESIGN AND METHODS: This was a prospective observational study to evaluate Intensive Care Units (ICU) of three public and two private hospitals in Trinidad with respect to their infrastructure, process of care and patient outcome. Structure of ICUs was assessed by interviews and personal observations. A Cost Block Model was used to determine the expenditure for ICUs. The process of ICU was assessed by Therapeutic Intervention Scoring System (TISS-28). For outcome evaluation, two prognostic scoring systems namely Simplified Acute Physiology Score (SAPS II) and Paediatric Index of Mortality-2 (PIM-2) were used RESULTS: The total number of ICU beds was 27. The overall bed occupancy was 66.2%. One hundred and eighteen patients consecutively admitted to ICU during a two-month period were enrolled for process and outcome evaluation. The overall median age of patients was 44 years [Interquartile range (IQR) 25, 59]. The mean cost per patient in the public hospitals was TT $64,746 compared to $77,000 in a private hospital. The average total daily TISS per patient was 27.01 +/- 5.4 (SD). The median length of stay was five days (IQR 2, 9). The overall predicted mortality was 32.9%, the observed mortality was 29.7% and thus the standardized mortality ratio (SMR) was 0.9. CONCLUSIONS: The overall bed availability in ICUs with respect to Trinidad and Tobago's population and case-mix is low compared to developed countries, although the process of ICU care is comparable. Outcome of patients was good in terms of risk-adjusted mortality. The study highlights the need to further increase bed-strength and optimize the resource utilization of ICUs in Trinidad and Tobago.

An evaluation of the intensive care unit resources and utilization in Trinidad / Una evaluación de los recursos y la utilización de las unidades de cuidados intensivos en trinidad

OBJECTIVES: To evaluate resources and utilization of Intensive Care Units in Trinidad and Tobago. DESIGN AND METHODS: This was a prospective observational study to evaluate Intensive Care Units (ICU) of three public and two private hospitals in Trinidad with respect to their infrastructure, process of care and patient outcome. Structure of ICUs was assessed by interviews and personal observations. A Cost Block Model was used to determine the expenditure for ICUs. The process of ICU was assessed by Therapeutic Intervention Scoring System (TISS-28). For outcome evaluation, two prognostic scoring systems namely Simplified Acute Physiology Score (SAPS II) and Paediatric Index of Mortality-2 (PIM-2) were used RESULTS: The total number of ICU beds was 27. The overall bed occupancy was 66.2%. One hundred and eighteen patients consecutively admitted to ICU during a two-month period were enrolled for process and outcome evaluation. The overall median age of patients was 44 years [Interquartile range (IQR) 25, 59]. The mean cost per patient in the public hospitals was TT $64,746 compared to $77,000 in a private hospital. The average total daily TISS per patient was 27.01 +/- 5.4 (SD). The median length of stay was five days (IQR 2, 9). The overall predicted mortality was 32.9%, the observed mortality was 29.7% and thus the standardized mortality ratio (SMR) was 0.9. CONCLUSIONS: The overall bed availability in ICUs with respect to Trinidad and Tobago's population and case-mix is low compared to developed countries, although the process of ICU care is comparable. Outcome of patients was good in terms of risk-adjusted mortality. The study highlights the need to further increase bed-strength and optimize the resource utilization of ICUs in Trinidad and Tobago.

OBJETIVOS: Evaluar los recursos y su utilización en las Unidades de Cuidados Intensivos en Trinidad y Tobago. DISEÑO Y MÉTODOS: Se trata de un estudio prospectivo observacional con el propósito de evaluar las Unidades de Cuidados Intensivos de tres hospitales públicos y dos privados en Trinidad, con respecto a su infraestructura, proceso de cuidado y respuesta clínica (resultado) del paciente. La estructura de las UCIs fue evaluada mediante entrevistas y observaciones personales. Un modelo de bloques del costo fue usado a fin de determinar los gastos en relación con las UCIs. El proceso de la UCI fue evaluado mediante el Sistema de Puntuación de Intervención Terapéutica (TISS-28). Para la evalua-ción del resultado clínico, se utilizaron dos sistemas de puntuación pronóstica, a saber, la puntuación simplificada de fisiología aguda (SAPS II) y el Índice Pediátrico de Mortalidad (PIM2). RESULTADOS: El número total de camas de UCI fue 27. La ocupación general de las camas fue de 66.2%. Los ciento dieciocho pacientes ingresados consecutivamente en la UCI durante un período de dos meses, fueron incorporados a la evaluación del proceso y los resultados. La edad mediana general de todos los pacientes fue de 44 años y el rango intercuartil (IQR) 25,59. El costo medio por paciente en los hospitales públicos fue TT $64 746 en comparación con $ 77 000 en un hospital privado. Según el TISS, el total promedio diario por paciente fue 27.01 ± 5.4 (SD). El tiempo mediano de estadía fue de 5 días (IQR 2, 9). La mortalidad general anticipada fue de 32.9%, la mortalidad observada fue de 29.7%, y por consiguiente la razón de mortalidad estandarizada (SMR) fue 0.9. CONCLUSIONES: La disponibilidad total de camas en las UCIs con respecto a la población y la casuística de Trinidad y Tobago, es baja en comparación con los países en desarrollo, aunque el proceso de cuidado de las UCIs es comparable. El resultado clínico de los pacientes fue bueno en términos de la...

Postal survey of cuffed or uncuffed tracheal tubes used for paediatric tracheal intubation.

A postal survey of the use of cuffed or uncuffed tracheal tubes for tracheal intubation in children and infants was performed to investigate the criteria used for deciding the choice of tube and the manner of inflating the cuff in the case of use of a cuffed tracheal tube (CTT). From 200 questionnaires despatched, replies were received from 130 paediatric anaesthesiologists (response rate 65%). In paediatric practice, the CTT was routinely used by 25% of respondents for more than 80% of their patients, while more than 37% of respondents use them in less than 20% of the cases. The three main criteria used for inflating a cuff were: (i) the presence of a leak, (ii) the type of surgery associated with the presence of a leak and (iii) the patient's age associated with the type of surgery and the presence of a leak. These criteria were specified, respectively, by 32%, 24% and 18% of the respondents. The cuff was inflated in response to a leak in 18% of the cases and as a response to a pressure manometer in 15% of the cases. Few paediatric anaesthesiologists use a cuffed tracheal tube routinely for tracheal intubation in children, and fewer actually use a pressure monitoring device, while it is suggested that the cuff pressure should be monitored in case of CTT.

Inferior vena cavectomy for nonexcisable Wilms' tumor thrombus.

Wilms' tumor with tumor extension into the vena cava is a not uncommon variant of tumor presentation. Typically, this extension is nonadherent to the endothelium and readily lends itself to removal either before or after chemotherapy. This case illustrates an unusual variant in which the tumor within the cava was tightly adherent to the venous wall and required the complete excision of the vena cava, left renal vein, and a portion of the iliac system.

A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes.

OBJECTIVE: To determine whether use of a primary pull-through would result in equivalent perioperative and long-term complications compared with the two-stage approach. SUMMARY BACKGROUND DATA: During the past decade, the authors have advanced the use of a primary pull-through for Hirschsprung disease in the newborn, and preliminary results have suggested excellent outcomes. METHODS: From May 1989 through September 1999, 78 infants underwent a primary endorectal pull-through (ERPT) procedure at four pediatric surgical sites. Data were collected from medical records and a parental telephone interview (if the child was older than 3 years) to assess stooling patterns. A similar group of patients treated in a two-stage fashion served as a historical control. RESULTS: Mean age at the time of ERPT was 17.8 days of life. Comparing primary ERPT with a two-stage approach showed a trend toward a higher incidence of enterocolitis in the primary ERPT group compared with those with a two-stage approach (42.0% vs. 22.0%). Other complications were either lower in the primary ERPT group or similar, including rate of soiling and development of a bowel obstruction. Median number of stools per day was two at a mean follow-up of 4.1 +/- 2.5 years, with 83% having three or fewer stools per day. CONCLUSIONS: Performance of a primary ERPT for Hirschsprung disease in the newborn is an excellent option. Results were comparable to those of the two-stage procedure. The greater incidence of enterocolitis appears to be due to a lower threshold in diagnosing enterocolitis in more recent years.

Behavioral interventions reduce infant distress at immunization.

OBJECTIVE: To assess the effectiveness of simple behavioral interventions at immunization on behavioral and biochemical indicators of distress in infants and parents in a primary care setting. DESIGN: Subjects were enrolled sequentially to control (standard care) and intervention groups. Intervention parents (n=57) were provided information about techniques to help their infants at immunization. Standard care parents (n=45) did not receive this information. Immunizations were videotaped and coded for infant and parent behaviors. Using a visual analog scale, parents rated their infant's and their own comfort at study enrollment, immediately after immunization, and at check-out. Saliva samples collected from infants and parents at study enrollment and at 15, 30, and 60 minutes after immunization were assayed for cortisol concentration by standard radioimmunoassay. Data were analyzed using chi2, analysis of variance, and general linear modeling. Patterns of salivary cortisol change after immunization were analyzed using hierarchical linear modeling. SETTING: A single, urban pediatric practice during 2 summers (1997 and 1998). SUBJECTS: Infants 2 to 24 months of age (n= 102) and their parents. MAIN OUTCOME MEASURES: Duration of infant distress (in seconds); parent use of behavioral intervention; infant and parent salivary cortisol concentrations (in nanomoles per liter). RESULTS: Intervention parents were more likely to use a behavioral technique with their infants before immunization (P<.05). Total infant distress was shorter for intervention infants at immunization (P<.01), and these infants were rated as more comfortable by their parents (P<.001) immediately after immunization. Salivary cortisol levels were lower for intervention infants at 15, 30, and 60 minutes after immunization (P<.05). CONCLUSION: Simple behavioral interventions before immunization are associated with reductions in behavioral and biochemical indicators of infant distress.

A study of the psychometric and predictive properties of the Fagerström Test for Nicotine Dependence in a population of young smokers.

This study examined the psychometric properties of the Fagerström Test for Nicotine Dependence (FTND) in a population (N = 7998) of young smokers entering US Air Force Basic Military Training (BMT). An exploratory factor analysis suggested that the FTND is comprised of two factors. The first factor, labeled Smoking Pattern, included items assessing the number of cigarettes smoked per day, time to first cigarette, difficulty refraining from smoking, and smoking when ill. The second factor, labeled Morning Smoking, consisted of two items measuring whether one smokes more in the morning and whether one would rather give up the first cigarette of the day or all others. The Smoking Pattern factor proved to have adequate internal consistency, impressive criterion-related validity, and was strongly related to smoking cessation 1 year following BMT. In contrast, the Morning Smoking factor demonstrated questionable psychometric properties and was not supported by a confirmatory factor analysis.

Results of derotational humeral osteotomy in posterosuperior glenoid impingement.

We identified 20 throwing athletes who continued to have pain after articular debridement for posterosuperior impingement syndrome. These patients were unable to resume sports, and we subsequently performed a derotational humeral osteotomy with a myorraphy of the subscapularis muscle. Patients were observed for an average of 46 months (range, 12 to 69). Eleven patients were able to resume the same sport at the same level, five resumed the same sport at a lower level, three changed sport secondary to persistent pain, and the last patient did not resume any sport and was worse after surgery. Patients returned to sports at an average of 6 months postoperatively (range, 4 to 44) and to their previous level of sports at an average of 12 months (range, 8 to 18). The mean increase in humeral retroversion was 29 degrees (range, 18 degrees to 44 degrees) Three women with preoperative multidirectional hyperlaxity were considered to have failed results. Derotational humeral osteotomy can be considered in the throwing athlete with posterosuperior impingement after failure of all other means of treatment. Careful patient selection and preoperative evaluation of humeral retroversion is important. Best results can be achieved in a motivated patient with low retroversion (< 10 degrees). If retroversion is normal (20 degrees to 30 degrees), the surgical indication is unclear. We do not recommend this surgery for patients with hyperlaxity.

Double-blind randomized prospective study of the efficacy of antibiotic prophylaxis for open reduction and internal fixation of closed ankle fractures.

Antibioprophylaxis has been proven to be efficient for some orthopaedic procedures. However, its efficacy for clean limited procedures with metallic implants is not clear. One hundred twenty-two closed ankle fracture patients undergoing open reduction and internal fixation were randomized, double-blindly, to receive either cephalothin (1 g i.v. every 6 h x four doses) or a placebo starting before tourniquet application. Mean trauma-surgery delay was 30.2 h, and average tourniquet duration was 65.4 min. Four patients (three of 62 on placebo and one of 60 on cephalothin) developed a superficial wound infection. One of the patients in the placebo group was hospitalized and treated with i.v. antibiotics. However, there was no osteomyelitis or premature hardware removal. The difference between the two groups was not statistically significant (chi 2 test of appreciation p = 0.33, two-tailed probabilities). Therefore, cephalothin prophylaxis does not seem justified in this patient population. A larger series is needed to avoid a type II error.

Tears of the supraspinatus tendon associated with "hidden" lesions of the rotator interval.

Exploration of the rotator interval during repair of 116 apparently "isolated" supraspinatus tendon lesions have revealed "hidden lesions" of the coracohumeral ligament, the superior glenohumeral ligament, and the superior portion of the subscapularis tendon in 19 cases. Epidemiologic characteristics were comparable with other series with the exception of involvement of the dominant shoulder in 95%. Arthroscopic computed tomography documented the lesion in 85% of the cases. At surgery the superficial layer of the coracohumeral ligament was always intact. After splitting of the rotator interval the lesion was visible and consisted of a local disinsertion of the common insertion of the superior glenohumeral ligament and the coracohumeral ligament and the deep superior fibers of the subscapularis tendon. It measured 1 to 2 cm in the superior-inferior direction. The biceps tendon was ruptured in 2 cases, subluxated in 14, and in its normal position in 5. The treatment consisted of intraosseous reinsertion of the supraspinatus tendon, recentering of the biceps, and reinsertion of the torn structures to reconstruct a functional pulley system. The patients have been reviewed with a mean follow-up of 20 months (range 12 to 36 months). A secondary rupture of the long head of the biceps has been observed in 25% of the cases after recentering of the tendon.

High transdermal fentanyl requirements in a patient with chronic cancer pain.

OBJECTIVE: To report a case of high transdermal fentanyl dosage requirements in a patient with chronic cancer pain. DATA SOURCES: Clinical studies, review articles, and relevant laboratory information. CASE SUMMARY: A 42-year-old woman with cervical cancer was admitted for control of her pain. Her outpatient analgesic regimen was a continuous intravenous infusion of morphine sulfate (MS) via an ambulatory infusion device. Upon admission, supplemental doses of intravenous MS were administered in an effort to eliminate the pain. Transdermal fentanyl therapy was initiated on hospital day 1 at 100 micrograms/h and the MS continuous intravenous infusion dosage was increased. Over the next four days, the patient experienced episodes of inadequate pain control and the transdermal fentanyl dosage was increased in increments of 100 micrograms/h. On hospital day 4 the MS continuous infusion was converted to patient-controlled analgesia (PCA). The patient reported acceptable pain control with a regimen of transdermal fentanyl 500 micrograms/h and MS via PCA and she was discharged home on hospital day 7. CONCLUSIONS: This patient's high transdermal fentanyl dosage requirement was related to disease progression. She experienced an acute pain episode that may have been effectively managed by increasing the dosage of her continuous intravenous MS infusion.