Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial.

BACKGROUND: To establish the role of antiemetic therapy with neurokinin-1 (NK1) receptor antagonists (RAs) in nonanthracycline and cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) regimens, this study evaluated single-dose intravenous (i.v.) fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with non-AC MEC. PATIENTS AND METHODS: In this international, phase III, double-blind trial, adult cancer subjects scheduled to receive ≥1 non-AC MEC on day 1 were randomized to a regimen comprising single-dose i.v. fosaprepitant 150 mg or placebo along with ondansetron and dexamethasone on day 1; control regimen recipients received ondansetron on days 2 and 3. Primary end points were the proportion of subjects achieving a complete response (CR; no vomiting and no use of rescue medication) in the delayed phase (25-120 h after MEC initiation) and safety. Secondary end points included CR in the overall and acute phases (0-120 and 0-24 h after MEC initiation, respectively) and no vomiting in the overall phase. Nausea and the Functional Living Index-Emesis were assessed as exploratory end points. RESULTS: The fosaprepitant regimen improved CR significantly in the delayed (78.9% versus 68.5%; P < 0.001) and overall (77.1% versus 66.9%; P < 0.001) phases, but not in the acute phase (93.2% versus 91.0%; P = 0.184), versus control. In the overall phase, the proportion of subjects with no vomiting (82.7% versus 72.9%; P < 0.001) and no significant nausea (83.2% versus 77.9%; P = 0.030) was also significantly improved with the fosaprepitant regimen. The fosaprepitant regimen was generally well tolerated. CONCLUSION: Single-dose fosaprepitant added to a 5-HT3 RA and dexamethasone was well tolerated and demonstrated superior control of CINV (primary end point achieved) associated with non-AC MEC. This is the first study to evaluate NK1 RA therapy as an i.v. formulation in a well-defined non-AC MEC population. CLINICALTRIALSGOV: NCT01594749 (https://clinicaltrials.gov/ct2/show/NCT01594749).

The United States needs a WHO health in prisons project.

Some facts about imprisonment in the USA are used to justify the comment that US is a country that loves prisons. The lack of provision of rehabilitative type services is stressed and the example of Valley Fever in one area of California demonstrates the public health disasters which can occur with the present arrangements. The organisations concerned with prisons seem to support the idea of prisons as a business. The article is a plea for a WHO health in prisons project as the way forward.

Ecology of Increasing Diseases: Population Growth and Environmental Degradation.

The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world.

Men and women have similar Q angles: a clinical and trigonometric evaluation.

The Q angle is an important determinant of patellar tracking, though its clinical relevance is debatable. One controversy centres around any possible differences in its value between men and women. The accepted, though unproven explanation, for the greater Q angle in women is that a woman has a wider pelvis. However, because of the long distance between the pelvis and patella, relative to the distance from the patella to the tibial tuberosity, large changes in the position of the anterior superior iliac spine are necessary to effect significant changes in the Q angle. In our study of 69 subjects, we did not find such large differences in the position of the anterior superior iliac spine, and found a mean difference of only 2.3 degrees between the Q angles of men and women. Furthermore, we found that men and women of equal height demonstrated similar Q angles, with taller people having slightly smaller Q angles. The slight difference in Q angles between men and women can be explained by the fact that men tend to be taller.

Applied biomechanics of the patella.

Although numerous prominent orthopaedists of the twentieth century considered the patella to be useless, even detrimental, it now is clear that the patella serves an important biomechanical function. It is a complex lever that magnifies the moment arm of the extensor mechanism. The patellofemoral contact area (the fulcrum of the lever) shifts along a proximodistal axis through the knee's arc of motion. As the knee flexes, the force within the patellar tendon diminishes relative to that of the quadriceps tendon. One's interpretation of patellar tracking is dependent on the choice of coordinates. When assessing tracking by way of anatomic coordinates, patellas are seen to be slightly lateralized at 0 degrees flexion and to follow similar paths down the trochlea. The tracking pattern is the result of an elaborate interplay between the quadriceps muscles, patellofemoral ligaments, the geometry of the trochlea, and the quadriceps angle. The articular cartilage of the patella is the thickest in the human body and does not follow the contour of the subchondral bone. Patellar cartilage is softer and more permeable than that of the trochlea. It is insensate. In size, nature, and number, the facets of the patellar articulation vary from person to person.

Performance and error analysis of automated external defibrillator use in the out-of-hospital setting.

STUDY OBJECTIVE: We determined whether automated external defibrillators (AEDs) can meet the American Heart Association performance criteria to detect and shock unstable cardiac rhythms (ventricular fibrillation [VF], ventricular tachycardia [VT]) in the setting of an out-of-hospital cardiac arrest. METHODS: AED performance was reviewed for cardiac arrests occurring between January 1, 1995, and December 31, 1997. After every cardiac arrest, data regarding each rhythm analyzed and subsequent response (shock or no shock) were downloaded from the AED memory module. The study paramedic and study physician independently reviewed each case and interpreted cardiac rhythms from downloaded AED data. The emergency medical services medical director resolved all discrepancies in a blinded manner. All cases of out-of-hospital cardiac arrest in which an AED was turned on and a rhythm analyzed were included. The primary objective was the correct identification and defibrillation of VF or VT. Sensitivity, specificity, and predictive values with 95% confidence intervals (CIs) were calculated. Sources of error in AED rhythm management are also described. RESULTS: A total of 3,448 AED rhythms were available for interpretation. Sensitivity and specificity for appropriate AED management of a shockable (VF or VT) rhythm were 81.0% (95% CI 77.9% to 83.8%) and 99.9% (95% CI 99.7% to 100%), respectively. Positive and negative predictive values were 99.6% (95% CI 98.7% to 99.9%) and 95.5% (95% CI 94.7% to 96.2%), respectively. There were 132 errors associated with AED management. Two errors resulted in delivery of an inappropriate shock. In the remaining 130 errors, a shockable rhythm was not shocked. Fifty-five (42.3%) errors were AED dependent, 70 (53.9%) were operator dependent, and 5 (3.9%) were unclassified. CONCLUSION: The AED had high specificity and moderately high sensitivity in detecting and shocking unstable cardiac rhythms in the out-of-hospital setting. Few cardiac rhythms were mismanaged by the AED. Elimination of operator-dependent errors could increase AED sensitivity.

Unit management of depression of patients with multiple sclerosis using cognitive remediation strategies: a preliminary study.

Multiple sclerosis (MS) is a chronic, often progressive neurologic disorder characterized by cerebral and spinal cord lesions. Patients with advanced MS often require continuous supervision in a long-term skilled nursing facility. Many of these patients experience clinical levels of depression. For this experiment, we randomly assigned MS patients living in a skilled nursing facility to either a control condition or an extended treatment protocol. The protocol consisted of assigning individual certified nursing assistants (CNAs) to each patient, in-service training for the CNAs, and the use of memory notebooks. All patients completed the short version of the Beck Depression Inventory and several measures of cognitive functioning at the start and end of the study. The results indicate statistically and clinically significant improvements in the depression of patients in the treatment but not in the control condition. These results led to recommendations for the treatment of MS patients living in long-term skilled nursing facilities and for additional research.

Combined erbium:YAG laser resurfacing and face lifting.

Facial aging occurs secondary to gravity-induced tissue ptosis and photoaging. Combined face lifting and carbon dioxide laser resurfacing provides a comprehensive one-stage approach to facial rejuvenation but is condemned by many plastic surgeons due to the nonspecific thermal effects of the laser and risk of skin necrosis. Newer high-energy erbium:YAG lasers allow precise tissue ablation with minimal thermal effect. In this study, various facial rejuvenation techniques were combined with simultaneous erbium:YAG laser resurfacing to assess results and complications. A total of 257 patients from Florida, Melbourne, Australia, and Tel Aviv, Israel, underwent combined erbium:YAG laser resurfacing and surgical facial rejuvenation. Various face-lift methods were used, including endoscopic, deep plane, and subcutaneous. Simultaneous, full-facial laser resurfacing was performed using a variety of erbium:YAG lasers. It was found that combined laser resurfacing and face lifting was successful in greater than 95 percent of patients with minimal morbidity. Two patients (1 percent) (both heavy smokers) developed small areas of skin necrosis that healed with minor pigment changes. Five patients (2 percent) developed synechia that was treated with no residual effect. Two additional patients (1 percent) developed temporary ectropion. There were no other cases of scarring, infection, or cosmetically obvious hypopigmentation. Although larger studies are necessary, it seems that the lack of thermal injury from the erbium:YAG laser makes it possible to safely perform laser resurfacing with surgical facial rejuvenation in nonsmokers. However, the authors caution that familiarity with the nuances of erbium:YAG laser resurfacing be obtained before performing combined laser resurfacing and face lifting.

Neuropsychological issues in the assessment of refugees and victims of mass violence.

Brain injury, stressor severity, depression, premorbid vulnerabilities, and PTSD are frequently intertwined in trauma populations. This interaction is further complicated when the neuropsychologist evaluates refugees from other cultures. In addition, the observed psychiatric symptoms reported in refugees and victims of mass violence may in fact not be the primary features of PTSD and depression but psychiatric symptoms secondary to the effects of traumatic brain injury. This paper reviews the occurrence of starvation, torture, beatings, imprisonment, and other head injury experiences in refugee and POW populations to alert treators to the presence of chronic and persistent neuropsychiatric morbidity, with implications for psychosocial adjustment. The concept of fixed neural loss may also interact with environmental and emotional stresses, and a model of neuropsychological abnormalities triggered by traumatic events and influenced by subsequent stress will also be considered. Neuropsychologists working with refugees play an important role in assessing the possibility of traumatic brain injury with tools that are relatively culture-fair.

Postoperative laser care.

Postoperative laser care is critical to the successful performance of CO2 and erbium laser resurfacing. Anticipation and prevention of postoperative problems and complications leads to greater patient satisfaction and fewer permanent sequalae. In most situations, a team approach, with the use of trained nurses and aestheticians, ensures greater success in this critical postoperative period. Laser resurfacing is one of the few procedures in which the surgery is only beginning when the surgeon leaves the operating suite.

Simultaneously combined ER:YAG and carbon dioxide laser (derma K) for skin resurfacing.

The simultaneously combined Er:YAG and carbon dioxide laser is ideally suited for treating deeper wrinkles with greater accuracy than either laser alone. By combining the precise ablative properties of the Er:YAG laser with the coagulative properties of the carbon dioxide laser, it is possible to control the depth of skin resurfacing to minimize complications and improve difficult and substantial wrinkles.

Anesthesia of six-week-old New Zealand White rabbits for thoracotomy.

Many methods of administering surgical anesthesia to rabbits have been described. We are studying the effects of anterior thoracic spinal procedures on the growth of young rabbit spines. We introduce a method for intubation using direct laryngoscopy without the need for specially manufactured or costly equipment and for administration of anesthesia applicable to six-week-old New Zealand White (NZW) rabbits. Induction of anesthesia was initiated with 5% isoflurane in a sealed plastic anesthesia box. No premedication was given. We performed direct laryngoscopy by using an otoscope. Under direct visualization, a 5-French polypropylene catheter was passed through the speculum of the otoscope and advanced through the vocal cords. The endotracheal tube without the adapter then was advanced over this guide. A vigorous cough reflex was noted as the tube passed through the vocal cords. We have found this cough reflex to be a very reliable indicator of correct placement. Throughout the surgical procedure, anesthesia was maintained with isoflurane delivered from a standard small-animal anesthetic machine using pediatric breathing hoses, y-piece, and ventilator. Recovery after surgery was rapid.

The effect of valproic acid on blood loss in patients with cerebral palsy.

Valproic acid (VPA) is used in the treatment of seizure disorders often present in patients with cerebral palsy. The charts of 114 patients with cerebral palsy were reviewed to evaluate the effect of VPA on blood loss during spine surgery. Forty-one patients had seizure disorders. Of these, 18 were taking VPA as monotherapy (group III) and the remaining 23 patients were taking other antiseizure medications, including two taking VPA (group II). There was a significant increase in the number of patients with abnormal bleeding times and a significant difference (p < 0.001) in blood loss (ml/kg) in patients taking VPA as monotherapy (38.6 ml/kg vs. 30.0 ml/kg). There was also increased blood-product administration postoperatively in the VPA monotherapy patients. Physicians should be aware of this potential association between VPA use and increased blood loss. The routine laboratory tests of complete blood count, prothrombin time, and partial thromboplastin time will not adequately screen for the platelet-mediated effects of VPA.

Erbium laser resurfacing: current concepts.

Laser skin resurfacing has enjoyed great popularity in recent years with the introduction of computerized, pulsed carbon dioxide lasers. However, the morbidity and side effects of carbon dioxide lasers have stimulated a search for alternative methods of skin remodeling. The erbium:YAG laser can be successfully used for skin resurfacing, with lower morbidity than the carbon dioxide laser. In a series of 625 patients who had erbium:YAG resurfacing, the following conclusions were reached. (1) Long-term (> 6 months) improvement in wrinkles and acne scars required total fluences exceeding 20 J/cm2. Periocular wrinkles required total fluences of between 20 and 40 J/cm2, depending on the depth of the wrinkles and skin thickness. Perioral rhytids required total fluences of between 40 and 80 J/cm2, whereas the cheeks and forehead required total fluences of 30 to 60 J/cm2. (2) Deeper wrinkles were best treated with a combination of erbium and carbon dioxide lasers, which minimized the bleeding that occurs with deeper erbium resurfacing. The simultaneous combined erbium with carbon dioxide laser was particularly advantageous. (3) Complications were relatively uncommon using the scanning erbium laser, and most adverse effects occurred early in the series. Scarring occurred in 5 of the 625 patients (0.8 percent) and mostly resolved with intralesional steroids. Hyperpigmentation occurred in 21 of the 625 patients (3.4 percent) and was temporary in nature. Hypopigmentation, which became evident after 6 months, occurred in 25 of the 625 patients (4.0 percent) but was mild and not a significant cosmetic problem, except in one patient who developed scarring on the neck. Hypopigmentation seemed to be related to the depth of resurfacing. Four of the 625 patients (0.6 percent) developed temporary scleral show, but no patients had permanent ectropion. Eight of the 625 (1.3 percent) developed synechiae under the lower eyelid, which required minor correction.

Modulated dual mode erbium/CO2 lasers for the treatment of acne scars.

BACKGROUND: Treatment of acne scarring is a challenging problem for dermatologists and cosmetic surgeons. Combining skin resurfacing with other procedures, especially the use of filling agents, has proven to be superior to the use of a single modality. Carbon dioxide laser resurfacing has been popularized for the treatment of acne scarring, but post operative morbidity with stimulation of active acne has been problematic. Conventional erbium resurfacing is effective when sufficient fluences are used, particularly when treating relatively superficial acne scars. Deeper resurfacing for acne scars is difficult with erbium lasers, owing to bleeding and heavy exudation, which decreases ablation efficiency and makes 'end points' difficult to visualize. The newer modulated hybrid erbium/CO2 lasers (Derma K, ESC Sharplan, Yokneam, Israel) produce efficient ablation by the reduction of bleeding, yet at the same time incur little post operative morbidity. This is suitable for treating deeper acne scars, and may be combined with other procedures, e.g. fat grafting. Of particular importance is the lack of acne stimulation associated with the use of the erbium/CO2 hybrid lasers. RESULTS: In my series of 78 patients, improvement in acne scarring was > 70% in the majority of patients. Post operative morbidity and complications were minor compared to conventional CO2 laser resurfacing.

Late neurocognitive changes from neurological damage following coronary bypass surgery.

A detailed case study with neuropsychological data over a 26-year period was used to explore the relationship between neurocognitive vulnerability preoperatively and subsequent neurocognitive decline identified several years postoperatively. Guidelines regarding the importance of neuropsychological assessment of intelligence, attention, memory, language, and visual-spatial planning and organizational skills are provided. Such evaluations clarify postoperative treatment planning because rehabilitation of cardiac patients with premorbid neurocognitive deficits poses special rehabilitation problems. With a detailed neurologic history as part of the preoperative evaluation, healthcare providers can identify acute and subtle risk factors for postoperative neurologic syndromes. This may lead to interventions designed to provide increased patient and family support.

Description of mothers with ADHD with children with ADHD.

Pilot data demonstrating the personality traits and background variables of ADHD mothers with children with ADHD are presented. Three subject groups are compared: mothers with ADHD, with ADHD children; mother without ADHD, with ADHD children; and mothers without ADHD, without ADHD children. Significant differences are observed on the Wender Utah Scale for attention deficit disorder, levels of neuroticism and conscientiousness on the NEO-Five Factor Inventory are significantly higher in mothers with ADHD. In addition, neuropsychiatric disorders, alcoholism in the family of origin, and atypical sexual events are reported at a significantly higher rate in the mothers with ADHD, with ADHD children. The implications of group differences are discussed.