Nassau University Medical Center

BACKGROUND: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

To ascertain whether exercise could prevent involutional bone loss, we studied 18 postmenopausal women, half of whom exercised for 1 h three times a week. Total and regional bone mass were measured before and after 1 year of exercise by the techniques of total-body neutron activation analysis (total body calcium) and photon absorptiometry (bone mineral content) of the distal radius. Total body potassium was measured by whole body counting. Bone mineral content and total body potassium did not change significantly in either group. Total body calcium increased in the exercise group from 781 +/- 95 g of 801 +/- 118 g (SD). In contrast, total body calcium decreased in each subject in the sedentary group. The daily calcium balance derived from the difference in total body calcium measurements was significantly different in the two groups of women (P less than 0.001). These data support the hypothesis that exercise can modify involutional bone loss.

Two hundred women were interviewed within 24-36 hours after giving birth. The patients were not examined. It was found that 56% of the patients suffered from low-back pain during pregnancy. The percentage of Caucasians was statistically higher in the back pain group. The percentage of Hispanics was statistically higher in the no pain group. Among the variables that were compared in both groups were the age, the weight gained by the mothers during pregnancy, the baby's weight, the number of previous pregnancies, number of prior children. None of the variables reached a statistically significant level. The pain group complained of pain the low-back area, which radiated in 45.5% of cases to the lower extremities. In about one-third of the patients the pain increased as the day wore on, whereas in another one-third the pain increased during the night and disturbed sleep. Standing, sitting, forward bending, lifting, and walking tended to increase the pain. Most of the patients started suffering from back pain between the fifth and seventh months of pregnancy. Several theories to explain the occurrence of backache during pregnancy are discussed.

Colitis and infection due to Clostridium difficile have been reported in patients receiving antineoplastic chemotherapy for cancer without prior antibiotic treatment. Chemotherapeutic agents can alter the normal bowel flora and cause extensive intestinal inflammatory changes, potentiating both the growth of C. difficile and its production of toxin. This review includes all 23 known reported cases of C. difficile infection associated with antineoplastic chemotherapy and examines the pathogenesis, clinical features, and management of this condition. Chemotherapy-associated C. difficile colitis has been documented in association with a variety of neoplasms. Various classes of antineoplastic agents have been incriminated, methotrexate most commonly. A spectrum of illness ranging from mild to fulminant has been reported. Symptoms, management, and outcome have appeared to be no different than for antibiotic-associated cases, but the available data are limited. Chemotherapy-associated infection with C. difficile may be underreported because it is not suspected and/or because frequent concomitant use of antibiotics masks its true incidence. C. difficile infection should be kept in mind whenever a patient undergoing antineoplastic chemotherapy develops diarrhea. Prompt, appropriate diagnostic testing and early treatment may avert morbidity and death.

Mineola, N.Y. From the Plastic and Maxillofacial Services of the Nassau County Medical Center and Nassau Hospital. Station Plaza North 222 Front Street Mineola, N.Y. 11501

CONTEXT: Many changes in health care delivery, health legislation, and the physician workforce that affect the supply and demand for endocrinology services have occurred since the first published workforce study of adult endocrinologists in 2003. OBJECTIVE: The objective of the study was to assess the current adult endocrinology workforce data and provide the first analysis of the pediatric endocrinology workforce and to project the supply of and demand for endocrinologists through 2025. DESIGN: A workforce model was developed from an analysis of proprietary and publicly available databases, consultation with a technical expert panel, and the results of an online survey of board-certified endocrinologists. PARTICIPANTS: The Endocrine Society commissioned The Lewin Group to estimate current supply and to project gaps between supply and demand for endocrinologists. A technical expert panel of senior endocrinologists provided context, clinical information, and direction. MAIN OUTCOME MEASURES: The following were measured: 1) the current adult and pediatric endocrinology workforce and the supply of and demand for endocrinologists through 2025 and 2) the number of additional entrants into the endocrinology work pool that would be required to close the gap between supply and demand. RESULTS: Currently there is a shortage of approximately 1500 adult and 100 pediatric full-time equivalent endocrinologists. The gap for adult endocrinologists will expand to 2700 without an increase in the number of fellows trained. An increase in the prevalence of diabetes mellitus further expands the demand for adult endocrinologists. The gap can be closed in 5 and 10 years by increasing the number of fellowship positions by 14.4% and 5.5% per year, respectively. The gap between supply and demand for pediatric endocrinologists will close by 2016, and thereafter an excess supply over demand will develop at the current rate of new entrants into the work force. CONCLUSIONS: There are insufficient adult endocrinologists to satisfy current and future demand. A number of proactive strategies need to be instituted to mitigate this gap.

CONTEXT: Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such conditions can be stressful for patients and their families and have historically been difficult to diagnose, especially at the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once variants in SRY and NR5A1 have been ruled out, there are few other single gene tests available. OBJECTIVE: We used exome sequencing followed by analysis with a list of all known human DSD-associated genes to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis. DESIGN: Samples were either submitted to the research laboratory or submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing data were filtered using a list of genes known to be involved in DSD. RESULTS: We were able to identify a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding, an additional 12.5% with likely pathogenic findings, and 15% with variants of unknown clinical significance. CONCLUSIONS: Early identification of the genetic cause of a DSD will in many cases streamline and direct the clinical management of the patient, with more focused endocrine and imaging studies and better-informed surgical decisions. Exome sequencing proved an efficient method toward such a goal in 46,XY DSD patients.

BACKGROUND: Radiation safety is an essential component in the treatment of patients with thyroid diseases by ¹³¹I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. METHODS: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection [corrected] recommendations formed the basic structure of the recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. RESULTS: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with ¹³¹I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. CONCLUSION: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with ¹³¹I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with ¹³¹I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.

BACKGROUND: The current study was designed to examine whether a combination of three nutrients, consisting of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS). METHODS: Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks. RESULTS: Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 +/- 0.5 kg of BW while those supplemented with the placebo gained 0.37 +/- 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 +/- 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 +/- 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 +/- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 +/- 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation. CONCLUSIONS: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

Traumatic brain injury (TBI) occurs when a blow or jolt to the head or a penetrating injury results in damage to the brain. It is the most frequent cause of hospitalization in young people with a higher prevalence in men. TBI is the leading cause of disability and mortality between the ages 1 and 45. TBI can be caused either by the direct result of trauma or due to a complication of the primary injury. The most common etiological factors for TBI are falls, road traffic accidents, violent physical assaults, and injuries associated with athletic activities. Following TBI, significant neurologic complications may occur which include seizures, dementia, Alzheimer's disease, and cranial nerve injuries. In addition, people may suffer from various psychiatric complications such as depression, posttraumatic stress disorder, generalized anxiety disorder, obsessive-compulsive disorder, and other cognitive and behavioral sequel that might significantly increase the comorbidity of the victims. Considering all of the above complications, TBI is one of the significant public health burdens. Literature has shown that only about 25% of people achieve long-term functional independence following TBI. In this paper, we focused not only on the epidemiology but also the etiology, complications following TBI and understanding their underlying pathogenesis. Further, we focused on analyzing the options to improve the treatment and rehabilitation following TBI in future.

Abstract One hundred and fifteen consecutive patients with documented active tuberculosis were skin-tested with three different tuberculin preparations, each of which reportedly contained 5 Tuberculin Units (5 TU) of purified protein derivative (PPD). A surprising lack of uniformity was demonstrated. Commercial antigen (PPD-PD) was associated with negative (0 to 4 mm) reactions in 49 per cent and doubtful (5 to 9 mm) reactions in 10 per cent of these patients. Purified protein derivative standard (PPD-S) gave 34 per cent negative and 3 per cent doubtful reactions. PPD stabilized with Tween-80 resulted in negative reactions in 17 per cent and doubtful reactions in 2 per cent of patients. A major factor in these false and nonpositive results appears to be loss of potency of the antigen through adsorption. Nonstabilized preparations are probably delivering less antigen than stated by the manufacturer, and this point is of great importance at low doses (i.e., 5 TU).

OBJECTIVES: To empirically define a "delay" for hip fracture surgery based on clinical outcomes, and to identify patient demographics and hospital factors contributing to surgical delay. DESIGN: Retrospective database analysis. SETTING: Hospital discharge data. PATIENTS/PARTICIPANTS: A total of 2,121,215 patients undergoing surgical repair of hip fracture in the National Inpatient Sample between 2000 and 2009. INTERVENTION: Internal fixation or partial/total hip replacement. MAIN OUTCOME MEASUREMENTS: Logistic regressions were performed to assess the effect of surgical timing on in-hospital complication and mortality rates, controlling for patient characteristics and hospital attributes. Subsequent regressions were performed to analyze which patient characteristics (age, gender, race, comorbidity burden, insurance status, and day of admission) and hospital factors (size, teaching status, and region) independently contributed to the likelihood of surgical delay. RESULTS: Compared to same-day surgery, each additional day of delay was associated with a significantly higher overall complication rate. However, next-day surgery was not associated with an increased risk of in-hospital mortality. Surgery 2 calendar days (odds ratio: 1.13) and 3+ days (odds ratio: 1.33) after admission was associated with higher mortality rates. Based on these findings, "delay" was defined as surgery performed 2 or more days after admission. Significant factors related to surgical delay included comorbidity score, race, insurance status, hospital region, and day of admission. CONCLUSIONS: Surgical delay in hip fracture care contributes to patient morbidity and mortality. A variety of patient and hospital characteristics seem to contribute to surgical delay and point to important health care disparities. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

ABSTRACT Subjects were 12 boys (12–14 yrs old) who had previously been diagnosed for hyperactivity (clinical group) and 15 age‐matched normal controls. For the selective attention (SA) task vertex ERPs were recorded to dichotically presented tone pips, with differing frequencies to each ear. Each series contained randomly interspersed signals and subjects were instructed to count the signals to one ear (targets). Behavioral tasks consisted of responses to SA targets, a 10‐min vigilance series, and dichotic listening. No significant group differences were found to non‐attended channels for N and P amplitudes and latencies. N amplitude enhancements to the attended channels were significant for the controls (44%), but not for the clinical boys (14%). Also, P latencies and amplitudes to the target pips were significantly greater for the control than the clinical group. Behavioral responses showed significant deficits by the clinical boys for SA and vigilance, but not for dichotic listening. Correct behavioral SA responses correlated significantly with P target amplitudes, but not with N amplitude enhancements. These findings indicate severe dysfunctions by the clinical boys for selective attention, involving both stimulus and response sets.

Mortality remains very high among septic patients despite the advanced treatments rendered in intensive care units. The development of septic shock is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Cytokines (tumor necrosis factor, interleukin-1, interleukin-6, interleukin-8, high-mobility group box-1 protein, macrophage migratory inhibitory factor) and noncytokines (nitric oxide, platelet-activating factor, complements, and eicosonoids) may inflict tissue injury and contribute to multiple organ dysfunction and cell death (or apoptosis). Gram-negative bacteria are the most common organisms identified in septic patients. The pathological effects of gram-negative bacteria are conveyed through lipopolysaccharide derived from the bacterial cell membrane. Lipopolysaccharide activates the nuclear factor kappa B, which triggers the release of inflammatory mediators. Protein components from gram-positive bacteria, fungi, or viruses may evoke the activation of nuclear factor kappa B in a similar fashion as lipopolysaccharide. Endogenous anti-inflammatory mediators are released in response to the infection and act to control the overwhelming systemic inflammatory response. The fragile balance between negative and positive feedback on the inflammatory mediators is the key factor that modulates the cellular damage and influences the clinical outcome.

Cardiovascular diseases exert a significant burden on the healthcare system worldwide. This narrative literature review discusses the role of artificial intelligence (AI) in the field of cardiology. AI has the potential to assist healthcare professionals in several ways, such as diagnosing pathologies, guiding treatments, and monitoring patients, which can lead to improved patient outcomes and a more efficient healthcare system. Moreover, clinical decision support systems in cardiology have improved significantly over the past decade. The addition of AI to these clinical decision support systems can improve patient outcomes by processing large amounts of data, identifying subtle associations, and providing a timely, evidence-based recommendation to healthcare professionals. Lastly, the application of AI allows for personalized care by utilizing predictive models and generating patient-specific treatment plans. However, there are several challenges associated with the use of AI in healthcare. The application of AI in healthcare comes with significant cost and ethical considerations. Despite these challenges, AI will be an integral part of healthcare delivery in the near future, leading to personalized patient care, improved physician efficiency, and anticipated better outcomes.

Fifty randomly selected references from a single monthly issue of The American Journal of Surgery; Surgery, Gynecology and Obstetrics; and Surgery were evaluated for citation and quotation errors. Thirteen major and 41 minor citation errors were found in the three journals. Thirty-seven major quotation errors were identified. The data support the hypothesis that authors do not check their references or may not even read them. This hypothesis may be expanded to maintain that reviewers do not check references.

Since 1975, clinical studies have been carried out to determine whether radiation when combined with localized hyperthermia evokes improved tumor control compared to that achieved with radiation alone. Local tumor hyperthermia was achieved using radiofrequency inductive heating at 27.12 MHz. In bulky lesions (greater than 100 cm3), radiofrequency conductive heating at 13.56 MHz was also used. More than 100 lesions in 38 patients were treated with radiation alone and hyperthermia in combination with radiation. Most lesions were treated either twice a week or once a week, depending on radiation dose fractionation scheme used. The overall result of tumor control rate of the combined therapy is superior to radiation therapy alone (75% versus 46%; P less than 0.01). No enhanced normal tissue morbidity was seen following the combined therapy. The detailed analysis of the treatment results shows that the tumor control rate is dependent on dose per fraction, the total dose, and the initial tumor volume. The radiation alone, at high doses per fraction, was effective in controlling 80% of the lesions, if the tumor volume was less than 10 cm3, compared to 30% when the tumor volumes were larger. The combination therapy, on the other hand, effected 80% local tumor control regardless of the tumor volume. The importance of good thermal distribution within the tumor volume, selective heating of the tumor tissues and the sequence and time interval between the combined therapy is discussed.

The Mahalanobis–Taguchi system (MTS) is a relatively new collection of methods proposed for diagnosis and forecasting using multivariate data. The primary proponent of the MTS is Genichi Taguchi, who is very well known for his controversial ideas and methods for using designed experiments. The MTS results in a Mahalanobis distance scale used to measure the level of abnormality of “abnormal” items compared to a group of “normal” items. First, it must be demonstrated that a Mahalanobis distance measure based on all available variables on the items is able to separate the abnormal items from the normal items. If this is the case, then orthogonal arrays and signal-to-noise ratios are used to select an “optimal” combination of variables for calculating the Mahalanobis distances. Optimality is defined in terms of the ability of the Mahalanobis distance scale to match a prespecified or estimated scale that measures the severity of the abnormalities. In this expository article, we review the methods of the MTS and use a case study based on medical data to illustrate them. We identify some conceptual, operational, and technical issues with the MTS that lead us to advise against its use.

LEARNING OBJECTIVES: After reviewing this article, the participant should be able to: 1. Understand the most modern indications and technique for neurotization, including masseter-to-facial nerve transfer (fifth-to-seventh cranial nerve transfer). 2. Contrast the advantages and limitations associated with contiguous muscle transfers and free-muscle transfers for facial reanimation. 3. Understand the indications for a two-stage and one-stage free gracilis muscle transfer for facial reanimation. 4. Apply nonsurgical adjuvant treatments for acute facial nerve paralysis. SUMMARY: Facial expression is a complex neuromotor and psychomotor process that is disrupted in patients with facial paralysis breaking the link between emotion and physical expression. Contemporary reconstructive options are being implemented in patients with facial paralysis. While static procedures provide facial symmetry at rest, true 'facial reanimation' requires restoration of facial movement. Contemporary treatment options include neurotization procedures (a new motor nerve is used to restore innervation to a viable muscle), contiguous regional muscle transfer (most commonly temporalis muscle transfer), microsurgical free muscle transfer, and nonsurgical adjuvants used to balance facial symmetry. Each approach has advantages and disadvantages along with ongoing controversies and should be individualized for each patient. Treatments for patients with facial paralysis continue to evolve in order to restore the complex psychomotor process of facial expression.