Clubfoot relapse: does presentation differ based on age at initial relapse?

PURPOSE: Treatment of idiopathic clubfoot with the Ponseti method is now standard, but predicting relapse can be difficult. Most experts recommend bracing to the age of four years, but this can be challenging for families, and may not be necessary in all patients. The purpose of this study is to compare patterns of bracing and age of relapse to help determine if predictable patterns exist. METHODS: The 70 patients with idiopathic clubfoot treated initially with the Ponseti technique who had relapse of their clubfoot were identified. Relapse was defined as a return to casting or surgery due to recurrent deformity. Data collected included demographics, treatment and brace adherence. Patients who sustained initial relapse before the age of two years were compared with those who sustained initial relapse after the age of two years. RESULTS: In total 56% (39/70) had their initial relapse prior to age two years while 44% (31/70) were after age two years. Of the patients who relapsed prior to the age of two years, 28% (11/39) were adherent with bracing while 72% were non--adherent. For patients who initially relapsed after age two, 74% (23/31) were adherent with bracing while 26% were non-adherent (p < 0.001). Of those who had initial -relapse -prior to age two, a subsequent relapse was seen in 69% (27/39). CONCLUSION: Patients with idiopathic clubfoot who experienced recurrence prior to age two years are significantly more likely to be non-adherent with bracing than those who sustain recurrence after age two. After initial relapse prior to age two, bracing adherence does not affect likelihood of subsequent recurrence.

WITHDRAWN: Effect of Vibram FiveFingers Minimalist Shoes on the Abductor Hallucis Muscle.

Ahead of Print article withdrawn by publisher.

Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

An information revolution in orthopaedics.

With the established success of the National Joint Registry and the emergence of a range of new national initiatives for the capture of electronic data in the National Health Service, orthopaedic surgery in the United Kingdom has found itself thrust to the forefront of an information revolution. In this review we consider the benefits and threats that this revolution poses, and how orthopaedic surgeons should marshal their resources to ensure that this is a force for good.

Effects of exclusive formula or breast milk feeding on oxidative stress in healthy preterm infants.

BACKGROUND: Compared to formula, breast milk is considered to have superior antioxidant properties and consequently may reduce the occurrence of a number of diseases of prematurity associated with oxidative stress. AIMS: To test whether the antioxidant properties of breast milk in healthy premature infants are different to those of formula milk by comparing vitamin E levels in milk and determining the excretion of malondialdehyde (MDA) in urine. METHODS: Vitamin E was measured in the breast milk of 20 mothers who had given birth prematurely. Urinary MDA was measured in 10 exclusively breast milk fed and 10 exclusively formula fed healthy preterm infants receiving no vitamin supplements. MDA was measured after derivatisation with 2,4-dinitrophenylhydrazine and consecutive HPLC with UV detection. RESULTS: Urinary MDA concentrations were consistently very low (0.074+/-0.033 microM/mM Cr and 0.078+/-0.026 microM/mM Cr in breast and formula fed infants respectively) and not significantly different between healthy breast milk and formula fed infants. Both breast and formula milk contained satisfactory levels (0.3-3.0 mg/100 ml) of vitamin E. CONCLUSION: Antioxidant properties of both breast milk and formulae are sufficient to prevent significant lipid peroxidation in healthy premature infants.

Current problems and potential techniques in in vivo glucose monitoring.

Accurate in vivo monitoring of glucose concentration would be a valuable asset, particularly for management of diabetes and preterm infants during critical care. In vivo glucose monitoring devices can be divided into two categories: implanted and non-invasive. Extensive research into in vivo glucose monitoring over recent decades has not resulted in the widespread use of clinically reliable monitoring systems. For implanted devices, poor biocompatibility of the materials used for fabrication remains a major challenge, whilst progress in the commercial development of non-invasive devices is hampered by the problem of multiple interference between the detected signals and the biological components. In this review, the methods available for in in-vivo glucose monitoring are described and the associated problems are discussed.

Does human milk reduce infection rates in preterm infants? A systematic review.

One of the reasons for advocating human milk (HM) feeding for preterm infants is the belief that this provides the infant with a degree of protection from infection. Providing fresh HM for such infants is challenging for mothers and staff, and consequently it is important that its benefits are rigorously evaluated. Therefore a systematic review was undertaken to assess all publications concerned with human milk feeding and infection in very low birth weight (VLBW) preterm infants. Nine studies--six cohort and three randomised controlled trials (RCT)--were assessed using predefined criteria. Methodological problems included poor study design, inadequate sample size, failure to adjust for confounding variables, and inadequate definitions of HM feeding and outcome measures. In conclusion, the advantage of HM in preventing infection in preterm, (VLBW) infants is not proven by the existing studies. Recommendations are made regarding the methodology required for further study of this important topic.

The light still shines, but not that brightly? The current status of perinatal near infrared spectroscopy.

Efforts have been made to find new, non-invasive methods for assessing tissue oxygenation and haemodynamics, particularly in the brain of the fetus and the newborn infant. Near infrared spectroscopy (NIRS) is a developmental technique that provides just such a method, allowing calculation of variables such as cerebral blood flow and cerebral blood volume. It can also measure peripheral oxygen consumption. This review is based on our long experience of using NIRS. Basic principles, techniques, validation, and clinical applications are highlighted. Although more than two decades have passed since its introduction, NIRS remains very much a developmental technique, despite technical progression. A great deal more research is required for NIRS to become a routine clinical tool.

Effect of limb cooling on peripheral and global oxygen consumption in neonates.

AIM: To evaluate peripheral oxygen consumption (VO(2)) measurements using near infrared spectroscopy (NIRS) with arterial occlusion in healthy term neonates by studying the effect of limb cooling on peripheral and global VO(2). SUBJECTS AND METHODS: Twenty two healthy term neonates were studied. Peripheral VO(2) was measured by NIRS using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) was measured in each neonate before and after limb cooling. RESULTS: In 10 neonates, a fall in forearm temperature of 2.2 degrees C (mild cooling) decreased forearm VO(2) by 19.6% (p < 0.01). Global VO(2) did not change. In 12 neonates, a fall in forearm temperature of 4 degrees C (moderate cooling) decreased forearm VO(2) by 34.7% (p < 0.01). Global VO(2) increased by 17.6% (p < 0.05). CONCLUSIONS: The NIRS arterial occlusion method is able to measure changes in peripheral VO(2) induced by limb cooling. The changes are more pronounced with moderate limb cooling when a concomitant rise in global VO(2) is observed. Change in peripheral temperature must be taken into consideration in the interpretation of peripheral VO(2) measurements in neonates.

Effect of a change in global metabolic rate on peripheral oxygen consumption in neonates.

AIM: To evaluate the effect of an induced change in global metabolic rate on peripheral oxygen consumption (VO(2)) in healthy full term neonates. SUBJECTS AND METHODS: Twenty four healthy full term neonates were studied. Peripheral VO(2) was measured by near infrared spectroscopy (NIRS) using arterial occlusion and measurement of the oxyhaemoglobin (HbO(2)) decrement slope. Global VO(2) was measured by open circuit calorimetry. Global and peripheral VO(2) were measured in each neonate before and after a routine bath. Abdominal and forearm skin temperatures were also recorded. RESULTS: Nineteen neonates completed the study. Global VO(2) increased by 30.7% (p = 0.001), and peripheral VO(2) by 23.1% (p = 0.001). A correlation between the fractional changes in global and peripheral VO(2) was apparent (r = 0.76, p = 0.001). Abdominal skin temperature decreased by 0.8 degrees C (p = 0.001), and forearm skin temperature by 0.6 degrees C (p = 0.04). CONCLUSIONS: Measurement of peripheral VO(2) using NIRS with arterial occlusion is responsive to conditions that increase global metabolic rate. Any change in global VO(2) must be taken into consideration during the interpretation of peripheral VO(2) measurements in neonates.

An essential 'health check' for all medical devices.

In order to safeguard patient safety, all new or modified medical devices must be assessed for their safety and performance before they are used routinely in clinical practice. Most devices will carry a CE (Confirmity European) mark to demonstrate their safety, but many devices will require an alternative method of assessment. In this article, we discuss the procedures already in place, the significant gaps that exist in the system and the risk management issues. We consider the impact on research and clinical practice, and describe our comprehensive risk management system for objectively assessing the safety of any medical device.

RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck.

PURPOSE: Patients with recurrent squamous cell cancer of the head and neck (SCH&N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. METHODS AND MATERIALS: The eligibility requirements included SCH&N presenting as a second primary or recurrence > or =6 months after definitive RT to > or =45 Gy, with > or =75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by > or =6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m2 of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. RESULTS: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p = 0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p = 0.083). CONCLUSION: Repeated RT with concurrent chemotherapy as given in this study is a feasible approach for selected, previously irradiated patients with SCH&N and may produce increased median and 1-year survival rates compared with systemic chemotherapy trials reported in the literature. A randomized study should be conducted to compare these two different approaches.

A randomised controlled trial to compare methods of milk expression after preterm delivery.

OBJECTIVES: Primary: to compare sequential and simultaneous breast pumping on volume of milk expressed and its fat content. Secondary: to measure the effect of breast massage on milk volume and fat content. DESIGN: Sequential randomised controlled trial. SETTING: Neonatal intensive care unit, North Staffordshire Hospital NHS Trust. SUBJECTS: Data on 36 women were analysed; 19 women used simultaneous pumping and 17 used sequential pumping. INTERVENTIONS: Women were randomly allocated to use either simultaneous (both breasts simultaneously) or sequential (one breast then the other) milk expression. Stratification was used to ensure that the groups were balanced for parity and gestation. A crossover design was used for massage, with patients acting as their own controls. Women were randomly allocated to receive either massage or non-massage first. MAIN OUTCOME MEASURES: Volume of milk expressed per expression and its fat content (estimated by the creamatocrit method). RESULTS: Milk yield per expression was: sequential pumping with no massage, 51.32 g (95% confidence interval (CI) 56.57 to 46.07); sequential pumping with massage, 78.71 g (95% CI 85.19 to 72.24); simultaneous pumping with no massage, 87.69 g (95% CI 96.80 to 78.57); simultaneous pumping with massage, 125.08 g (95% CI 140.43 to 109.74). The fat concentration in the milk was not affected by the increase in volume achieved by the interventions. CONCLUSIONS: The results are unequivocal and show that simultaneous pumping is more effective at producing milk than sequential pumping and that breast massage has an additive effect, improving milk production in both groups. As frequent and efficient milk removal is essential for continued production of milk, mothers of preterm infants wishing to express milk for their sick babies should be taught these techniques.

Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti-epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m(2), followed by weekly infusions of 100 to 250 mg/m(2) for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).

A fuzzy system for detecting distorted plethysmogram pulses in neonates and paediatric patients.

Pulse oximetry is a useful, quick, non-invasive and widely used technology for monitoring oxygen saturation (SaO2) for neonates and paediatric patients. However, pulse oximetry is fraught with artefacts, causing false alarms resulting from patient or probe movement. The shape of the plethysmogram is a useful visual indicator for determining the reliability of SaO2 numerical readings. If certain features could be defined that tag valid plethysmogram pulses, then automatic recognition of valid SaO2 values can be attained. We observed that the systolic upstroke time (t1), the diastolic time (t2) and heart rate (HR) extracted from the plethysmogram pulse constitute features which can be used for detecting normal and distorted plethysmogram pulses. Therefore, we developed a knowledge-based system using fuzzy logic for classifying plethysmogram pulses into two categories: valid and artefact. A total of 22,497 pulse waveforms were used to define the system parameters. These were obtained from 13 patients with heart rates ranging between 62 and 209 beats min-1. A further 1420 waveforms obtained from another four patients were used for testing the system, and visually classified into 833 (59%) valid and 587 (41%) distorted segments. The system was able to classify 679 (82%) valid segments and 543 (93%) distorted segments correctly. The calculations of the system's performance showed 82% sensitivity, 86% accuracy and 93% specificity. We, therefore, conclude that the algorithm used in this system can be implemented in its present from for real-time SaO2 monitoring in intensive care for detecting valid and distorted plethysmogram pulses.