Neonatal mortality in the intervention clusters overall was increased antibiotic resistance food buy 3mg ivermectin with visa, which may have been due to overtreatment antibiotic resistance hospital acquired infections generic 3 mg ivermectin free shipping, as were maternal infections antibiotics effect on sperm purchase ivermectin 3 mg line. This trial has important implications for the setting infection 2 game effective ivermectin 3mg, implementation antibiotic lawsuit purchase ivermectin 3 mg online, and scale up of this intervention antimicrobial yoga towel buy 3mg ivermectin amex, notably that antenatal corticosteroids should be used in the context of more accurate assessment of gestational age and assessment for maternal infection; ensuring that maternal and newborn care can be provided should also be a part of this intervention antibiotic nomogram order ivermectin 3mg without prescription. In the Antenatal Corticosteroids Trial antibiotic rocephin generic ivermectin 3mg without prescription, half of the births were at home (Althabe and others 2015). Interventions to Reduce Maternal and Newborn Morbidity and Mortality 127 Antibiotics. The evidence does not support the routine administration of antibiotics to women in preterm labor with intact membranes in the absence of overt signs of infection (Flenady and others 2013). However, evidence is insufficient to determine the existence of neuroprotective benefits for infants of women with high-risk pregnancies at term (Nguyen and others 2013), and more research is needed. Limited evidence suggests that training of birth attendants improves initial resuscitation practices and reduces inappropriate and harmful practices (Carlo and others 2010; Opiyo and English 2010) but may not have a significant impact on perinatal mortality. This finding may be because advanced resuscitation, including intubation and drugs, is appropriate only in institutions that provide ventilation. This finding suggests that substantially more infrastructure may be necessary, in addition to provider training and community mobilization, to have a meaningful effect on neonatal outcomes. Ideally, this care should be provided by a skilled attendant; however, most of these tasks can be carried out at home by alternative attendants. Other important but less prevalent conditions include jaundice and hemorrhagic disease of the newborn. These conditions all have high fatality rates, particularly tetanus and encephalopathy (Lawn and others 2014). Preventive measures needed to adequately reduce this burden of disease include much of what has already been discussed. Other interventions include routine vitamin K administration in newborns for the prevention of vitamin K deficiency bleeding and early phototherapy for jaundice. Early phototherapy reduces both mortality and chronic disability subsequent to kernicterus and is feasible in facilities (Djik and Hulzebos 2012; Maisels and others 2012). Kangaroo mother care, which is part of the extra newborn care package for small and low-birthweight infants and includes continuous skinto-skin contact between mothers and newborns, frequent and exclusive breastfeeding, and early discharge from hospital, has been evaluated in comparison with conventional care in a Cochrane review. In low-birthweight infants, kangaroo mother care reduced neonatal mortality by 40 percent, hypothermia by 66 percent, and nosocomial infection by 55 percent. A meta-analysis shows that breastfeeding education or support (or a combination of education and support) increased exclusive breastfeeding rates (Haroon and others 2013). Pooled data from three community trials involving 54,624 newborns of cord care with chlorhexidine versus dry care show a reduction in omphalitis of 27 percent to 56 percent and in neonatal mortality of 23 percent (Imdad and others 2013). Chlorhexidine cord cleansing did not have these effects when used in hospital settings 128 Reproductive, Maternal, Newborn, and Child Health (Sinha and others 2015). Management of Neonatal Encephalopathy Seizures are common following perinatal hypoxic ischemia. Induced hypothermia (cooling) in newborn infants who are encephalopathic because of intrapartum hypoxia reduces neonatal mortality, major neurodevelopmental disability, and cerebral palsy. Cooling reduced neonatal mortality by 25 percent and the authors conclude that induced hypothermia should be performed in term and late preterm infants with moderate or severe hypoxic ischemic encephalopathy if identified before age six hours (Jacobs and others 2013). Routine anticonvulsant prophylaxis with barbiturates for the neuroprotection of term infants with perinatal asphyxia is not recommended (Evans, Levene, and Tsakmakis 2007). Institution of continuous positive airway pressure may bring down the requirement and cost of surfactant therapy (RojasReyes, Morley, and Soll 2012). Oral antibiotics administered in the community reduce all-cause mortality by 25 percent and pneumonia-specific mortality by 42 percent (Zaida and others 2011). Interventions in the Pipeline Household air pollution is recognized as a risk factor for several health outcomes, including stillbirth, preterm birth, and low birthweight, but rigorous evidence for the impact of reducing household air pollution on these birth outcomes is lacking (Bruce and others 2013). Interventions to reduce household air pollution may reduce poor perinatal outcomes. A habitual supine sleeping position has been associated with an increase in stillbirth (Owusu and others 2013). Whether sleeping position can be changed by advice or other interventions, and whether such a change would affect stillbirth rates, remains to be established. Chapter 17 of this volume (Horton and Levin 2016) summarizes the findings of a systematic search of the cost-effectiveness literature of reproductive, maternal, newborn, and child health interventions and discusses the difficulties, including methodological gaps, multiple platforms, and outcome measures. For other simple interventions, research has demonstrated convincingly that, if provided in the appropriate time and with the appropriate protocol, many more lives can be saved. Even in the poorest settings simple approaches at the family and community levels and through outreach services can save many lives now. Well-known interventions, such as neonatal resuscitation and case management of infections, can be added to existing programs, particularly Safe Motherhood and Integrated Management of Childhood Illness programs, at low marginal cost. Although community-based options are often most feasible, if the commitment to strengthen clinical care systems is lacking, the potential improvements in health outcomes from these options is limited. However, as increasing numbers of women and babies reach first-level facilities and hospitals, the quality of care challenges in these facilities need to be addressed. A shift in focus to quality of care has the potential to unlock significant returns for every mother and every newborn beyond 2015 to end preventable maternal and newborn deaths and stillbirths by 2030. Fever in children under age five years signifies systemic inflammation, typically in response to a viral, bacterial, parasitic, or less commonly, a noninfectious etiology. Evidence regarding fever incidence is variable, with country-specific reports from cross-sectional surveys or weekly active case detection ranging from two to nine febrile episodes per child under age five years per year, a mean of 5. National survey data from 42 SubSaharan African countries (excluding Botswana, Cabo Verde, Eritrea, and South Africa) were collected and analyzed for an estimated 655. At the health facility and community levels, fever is by far the most common pediatric presenting symptom. The decline of malaria incidence; rise of antimicrobial resistance; and availability of accurate, low-cost, point-of-care diagnostics have challenged the effectiveness of the presumptive treatment of febrile illnesses and reopened the discussion of the most accurate and cost-effective approaches for fever diagnosis and treatment. There are settings with very high malaria transmission and limited availability of diagnostic test where presumptive treatment would Corresponding author: Julie M. Mounting evidence demonstrated the decline of Plasmodium falciparum infections in response to intense national and multinational initiatives to control malaria. This new strategy is being implemented in the public sector in most Sub-Saharan African countries (Bastiaens and others 2011). However, many patients first present for care in the informal private sector, and more research is needed to better understand treatment decision making in this context and how to reduce overuse of antimicrobials and ensure appropriate care. The epidemiology of pediatric febrile illness is undoubtedly shifting; understanding the etiology of nonmalarial fevers in each context is the logical next step to improve pediatric clinical outcomes of other treatable serious febrile illnesses, such as pneumonia, sepsis, bacterial meningitis, enteric fever, rickettsioses, and influenza. Given rampant and expanding antimicrobial drug resistance globally, care must be taken to use antibiotics only when indicated and to develop careful guidelines when resources are limited. Present guidelines are based on clinical features that are unfortunately poorly predictive of the diseases causing fever. Low-cost, accurate, point-ofcare diagnostics are needed to determine which children can benefit from antibacterial therapies to guide the most effective use of antibiotics. This chapter discusses the evidence that informs current etiologies of fever, stratified by regional geography. It presents the clinical presentation, diagnosis, and treatment of the most common diseases, with special considerations for certain age groups, the burden of disease for different conditions, classification and treatment strategies, and a review of available diagnostic tests. Although these studies are informative, they need to be interpreted in the context of the individual study design and context. Although the available evidence suggests that most viral and some specific bacterial diseases, such as rickettsiosis and leptospirosis, are likely to be underdiagnosed, data are either not available or are limited from several countries where the fever burden is highest, such as the Democratic Republic of Congo, India, and Nigeria. Ongoing surveillance of fever etiology in multiple representative geographies to establish trends in predominant pathogens and to identify emerging infections early would be ideal. Additionally, little research is available on fever etiology of young infants (age 02 months); a concerted research effort is underway to better understand the distribution 140 Reproductive, Maternal, Newborn, and Child Health Table 8. Infectionrelated neonatal deaths contributed at least 10 percent to overall mortality in children under age five years in 2013 (Liu and others 2015). Care seeking for young infant illness often occurs too late or not at all, making community-based efforts critical to increasing access to early treatment and addressing this disproportionate morbidity and mortality. Sepsis Sepsis in young infants presents in two varieties: early onset (fewer than seven days after birth) and late onset (seven days or more). Early-onset neonatal sepsis is thought to be the result of exposure to pathogens in the maternal birth canal; late-onset sepsis is thought to be secondary to environmental exposures. Symptoms of bacteremia and related sepsis in young infants are often vague and may include fever, hypothermia, poor tone, jaundice, or inability to suck. A decrease in urine production, poor perfusion, bulging fontanelle, excessive sleepiness, or alternatively, excessive irritability are signs of more serious disease. Without antibiotic treatment, many young infants will rapidly progress to severe bacterial sepsis, which may prove fatal. A review by Ganatra and Zaidi (2010) of five neonatal sepsis studies reports incidences of blood culture confirmed early-onset sepsis ranging from 2. Although a positive blood culture is the gold standard for diagnosing bacteremia, cultures are known to lack sensitivity, especially in children, and may take several hours to days before results are available; cultures require significant laboratory infrastructure, which is a challenge in low-resource settings. Total leukocyte count, leukocyte differential, levels of acute phase reactants (for example, C-reactive protein), and screening panels using a variety of cytokine markers may provide supportive evidence of infection when abnormal, but these measures have been shown to have limited value in diagnosing bacteremia (Remington and others 2006). According to a systematic review of 27 studies performed by Waters and others (2011), the most common documented pathogens for early-onset sepsis (N = 282 isolates) include Escherichia coli (16. These results suggest that empiric antibiotic regimens for both early- and late-onset sepsis should be broad spectrum to treat both gram-positive and -negative infections. A lumbar puncture to check for pleocytosis (an elevated number of white blood cells in cerebral spinal fluid), elevated protein, or low glucose levels can indicate whether infection is present in the central nervous system. The presence of leukocyte esterase, blood, or nitrates may suggest a bacterial urinary infection, however, only if the urine sample is not contaminated. The difficulty of obtaining a sterile sample from a young infant has made implementation of this test less feasible in the community setting. Variable incidence levels have been reported, with Sub-Saharan Africa reporting rates almost threefold higher than North and South America. This disparity may be due to differences in study design, previous antibiotic use, and the severity of illness, with young infants dying before they can be fully evaluated. It is difficult to disentangle primary respiratory infections from sepsis and other pulmonary conditions related to premature lungs and congenital anomalies. Viral respiratory infections often infect the smallest of airways- bronchioles-causing inflammation, bronchospasm, and difficulty breathing. An assessment of the global burden of severe pneumonia 144 Reproductive, Maternal, Newborn, and Child Health estimated that in 2010, 11. The Pneumonia Etiology Research for Child Health project was designed in response to the call for enhanced understanding of the etiology of pneumonia. Common viral etiologies of bronchiolitis include respiratory syncytial virus, influenza (types A and B), parainfluenza, human metapneumovirus, rhinovirus, adenovirus, coronaviruses, and human bocavirus (Garcнa and others 2010). The cost-effectiveness of an oxygen systems strategy compares favorably with other higher-profile child survival interventions, such as new vaccines (Duke and others 2008). Although most portable oxygen systems lack sufficient oxygen flow rates to provide adequate respite for increased work of breathing in infants with bronchiolitis, oxygen concentrators provide the most consistent and least expensive source of oxygen in health facilities with reliable power supplies. Future research efforts that focus on reducing the power needs of or using alternative energy sources for oxygen concentrators will facilitate their introduction to lower levels of the health care system. The capacity to perform routine maintenance and to source necessary replacement parts locally needs to be addressed if this technology is to be sustainable at the community or facility level. Viral Exanthems A discussion of febrile illnesses in children is incomplete without the mention of the myriad viruses that present nonfocally and ultimately declare themselves clinically with a characteristic exanthema or rash. Fast breathing is defined as respiratory rate 50 breaths per minute in infants age 212 months, and 40 breaths per minute in infants age 1259 months. Measles and, to a lesser extent, varicella are highly contagious viruses and have the potential for serious sequelae. Parvovirus B19 is an important condition to consider in patients with sickle-cell disease because infection can lead to aplastic anemia. Enteric Fever Enteric fever is an all-encompassing term for the disease caused by several serovars of Salmonella enterica including S. The clinical picture of typhoid is nonspecific with symptoms of severe headache, nausea, and loss of appetite associated with sustained, high fever and few other specific signs. However, treatment with antibiotics and prevention through vaccination are ultimately needed to reduce typhoid mortality and morbidity (United Nations 2013). Clinically, malaria ranges from asymptomatic parasitemia to uncomplicated malaria to severe malaria (typically manifested as cerebral malaria, severe anemia, hypoglycemia, and potentially multisystem organ failure). Further detail on etiology and control strategies for malaria can be found in volume 6 (Holmes, Bertozzi, Bloom, Jha, and Nugent, forthcoming). A paradigm shift has occurred in recent years, away from the presumption that all fevers in endemic areas should be treated as malaria toward the recommendation that laboratory testing should occur before treatment. Dengue and Chikungunya Virus Dengue fever, a mosquito-borne arbovirus of the genus Flavivirus, has become one of the most common and rapidly spreading vector-borne diseases after malaria and is a major international public health concern. Approximately 95 percent of cases occur in children younger than age 15 years; infants constitute 5 percent of all cases. Dengue has mainly been documented in Asia; data from Sub-Saharan Africa are lacking, although reports from Gabon and elsewhere are creating concern that it is an emerging disease or has been previously not recognized because of a lack of diagnostic testing (Caron and others 2013). No specific therapeutic agents exist for dengue fever apart from analgesics and medications to reduce fever. Treatment is supportive; steroids, antivirals, or carbazochrome, which decreases capillary permeability, have no proven role. Mild or classic dengue is treated with antipyretic agents such as acetaminophen, bed rest, and fluid replacement; most cases can be managed on an outpatient basis. The management of dengue hemorrhagic fever and dengue shock syndrome is purely supportive. Chikungunya, an alpha virus transmitted by mosquitoes of the Aedes genus, is responsible for a clinical syndrome characterized by fever, rash, headache, myalgias, and arthralgias (Thiboutot and others 2010). It can affect all ages, including young children; transplacental transmission with congenital infection has been described (Gйrardin and others 2008). Although past outbreaks of chikungunya have primarily occurred in Sub-Saharan Africa and regions of South Asia and East Asia and Pacific, this vector-borne viral infection has emerged in Latin America and the Caribbean, where it spread rapidly from island to island. However, the declining malaria burden in many endemic regions and an increasing programmatic focus on malaria elimination mean that novel target antigens, use of gold nanoparticles, or other diagnostic approaches may be needed to create point-of-care tests with increased sensitivity. Several diagnostic approaches are based on selective microscopic detection of infected blood cells by methods such as third-harmonic generation imaging (Bйlisle and others 2008), photoacoustic flowmetry (Samson and others 2012), and more recently, magneto-optical detection of the malaria pigment (Mens and others 2010) hemozoin using hand-held devices with polarized light and laser pulse detection of vapor nanobubbles generated by the parasite (Lukianova-Hleb and others 2014). Trials of algorithmic approaches have been undertaken at the community and facility levels to identify seriously ill children to indicate referral to a higher level of care. Further research is needed to identify best practice models for the formal and informal private sector to create a synergistic approach to providing appropriate treatment and referral to more advanced care, when needed. The classifications are color coded, with pink calling for hospital referral or admission, yellow for treatment at home, and green for children with mild illness who require only supportive care at home and can be counseled with return precautions (figure 8. In Bangladesh, a systematic evaluation of 669 sick children age 259 months, using a gold-standard physician diagnosis and treatment decision, found a sensitivity of 78 percent and specificity of 47 percent for identifying children with probable bacterial infections requiring antibiotics (Factor and others 2001). However, many children with bacteremia, skin infections, and dysentery would not have received antibiotics. This evaluation was based on a comparison with an expert diagnosis that is subject to clinical subjectivity and the limited accuracy of available diagnostic tools. No Malaria Risk and No Travel to Malaria Risk Area · No general danger signs · No stiff neck. Look for local tenderness; oral sores; refusal to use a limb; hot tender swelling; red tender skin or bolls; lower abdominal pain or pain on passing urine in older children. Other important complications of measles - pneumonia, stridor, diarrhoea, ear infection, and acute malnutrition - are classified in other tables. Unfortunately, the study also finds that this approach is not being used consistently in routine clinical practice. Problems included the failure to treat children in accordance with the guideline (incorrect choice of drug, dosage, and duration); missed opportunities for vaccination; treatment with unnecessary and occasionally dangerous medications; prescription of a large number of drugs for some children; and failure to perform counseling tasks, including how to administer medications (Rowe and others 2001). New training strategies are necessary, especially for respiratory rate measurement and identification of danger signs. A prospective hospitalbased study in Mozambique finds substantial symptom overlap between malaria and severe pneumonia among hospitalized children (Bassat and others 2011). A decision rule requiring the presence of any of these 12 signs had high sensitivity (87 percent) and specificity (74 percent). However, a simplified algorithm that required only seven signs-history of difficulty feeding, history of convulsions, movement only when stimulated, respiratory rate 60 breaths per minute, temperature 37. This clinical algorithm was validated at the community level during routine household visits in rural Bangladesh (Darmstadt and others 2011). A simplified six-sign algorithm had a sensitivity of 81 percent and specificity of 96 percent for screening neonates requiring referral, and sensitivity of 58 percent and specificity of 94 percent for identifying newborns at risk of dying. Although data are limited, multiple reviews cite widespread resistance to ampicillin and gentamicin among sepsis-causing common pathogens E. Although broad-spectrum cephalosporins show better sensitivities to most pathogens, they are expensive and their use will increase drug pressure. A more detailed discussion of this study is provided in chapter 18 in this volume (Ashok, Nandi, and Laxminarayan 2016). In Zambia, a cluster randomized controlled trial assessed the impact of training birth attendants to perform a modified neonatal resuscitation protocol for newborns with respiratory distress and to recognize a set of cardinal symptoms and signs of possible neonatal infection. If any signs of possible serious bacterial infection were observed in the first four weeks of life, intervention-trained birth assistants were to administer a 500 milligram dose of oral amoxicillin and facilitate referral to the nearest rural health center. This combination of interventions resulted in a 45 percent reduction in neonatal mortality for all live births in intervention as compared with controls (Gill and others 2011). Several studies from India, Nepal, and Pakistan evaluate a variety of community-based perinatal packages that deploy newborn home visitation; each trial has shown significant impact on neonatal mortality (Baqui and others 2008; Bhutta and others 2008; Kumar and others 2008). This study demonstrated more optimal newborn care practices in intervention clusters and a significant reduction of neonatal mortality only among babies born at home receiving intervention (hazard ratio intervention/control 0.
Situational factors that affect the validity of selfreported data refer to characteristics of the external environment in which the survey is being conducted bacteria 100x cheap 3 mg ivermectin free shipping. Many studies have found that youth are more likely to report engaging in sensitive behaviors when a survey is completed in a school setting rather than in their homes (Gfroerer et al antimicrobial journal buy cheap ivermectin 3mg on line. Four measures of various stages of the smoking uptake process were higher in the school-based survey antibiotics for dogs discount ivermectin 3 mg line, but estimates for current cigarette use and frequent cigarette use antibiotic joint spacer buy 3mg ivermectin amex, although elevated in the school-based survey virus vs bacteria purchase ivermectin 3 mg without a prescription, did not differ significantly from estimates generated in the household-based survey bacteria and viruses ivermectin 3mg without prescription. It is noteworthy that all three of these studies use self-administered rather than intervieweradministered interviews/questionnaires virus buster serge 3 mg ivermectin for sale. Nevertheless bacteria staphylococcus aureus safe 3 mg ivermectin, the privacy that school surveys provide is important, especially if smoking becomes more socially unacceptable over time. Household-based surveys, however, are more likely to include youth who drop out of school or are frequently absent from school, and youth in these groups are more likely to smoke. There was also a high level of agreement between self-reported current tobacco use and salivary cotinine tests among a combined sample of adults and youth (87. If these factors remain stable over the years, however, they should not affect the trends seen over time. Validity of Measures of Tobacco Use Among Adults All of the data on tobacco use among adults presented in this report were based on self-reported responses to questionnaires. Biochemical validation studies suggest that data on self-reported cigarette smoking are generally valid, except in certain situations, such as when data are collected in conjunction with intense smoking cessation programs or with certain populations, such as pregnant women (Velicer et al. Misclassification may also be more common among intermittent smokers, who may not classify themselves as smokers because they do not perceive themselves as being addicted or because of social desirability bias. Additionally, smokers may misreport the number of cigarettes they smoke per day because of "digit preference" (a preference for multiples of 10) (Klesges et al. Although self-reported data have been found to adequately reflect cigarette smoking patterns (including whether a respondent who has smoked in the past is currently not smoking) (Connor Gorber et al. It should be noted, however, that much of the research literature on the validity of selfreported data is restricted to cigarette smoking-and not measures of cessation or other tobacco products. High agreement was also found for self-reported information on current tobacco use and salivary cotinine among a combined sample of youth and adults (Tourangeau et al. Thus, a discussion of the factors that may affect validity is important so that the data presented in this report are interpreted with some caution and an understanding of possible sources of inaccuracy. Clearly, many factors can affect the validity of self-reported data, such as response biases and the particular methodologic features of the surveys. For example, methodologic differences in survey administration include but are not limited to timing, order of survey questions, sampling, mode of data collection. In addition, responses to questions may be subject to more social desirability biases in surveys that are focused solely on tobacco use versus those where tobacco use is just one of several health behaviors being assessed, as research has found that the context in which sensitive questions are asked can effect responses to survey questions (Tourangeau and Yan 2007; Krumpal 2013). Persons who smoked every day or some days were classified as current cigarette smokers. To be classified as a current smoker, students had to answer "yes" to questions about ever smoking and current smoking. In addition, students who were current smokers and reported smoking on 20 or more of the past 30 days were categorized as current frequent cigarette smokers. This measure was examined for youth because current frequent cigarette smokers most likely have a more established pattern of use and are more likely to smoke as adults, thereby potentially representing the future group of adult smokers who are trying to quit. Students who answered "yes" to ever smoke and "no" to currently smoke were categorized as (a) former daily smokers, if they answered "yes" to ever daily; or (b) former nondaily smokers, if they answered "no" to ever daily. Former smokers were defined as ever smokers who did not currently smoke at the time of the survey. Because smoking behaviors are less established among youth and young adults, this measure was not examined for those groups. For each smoking measure, the definitions used in the various surveys are summarized below. Adults, Young Adults, and Youth 117 A Report of the Surgeon General having smoked 100 cigarettes in their life but were not smoking at time of interview and had quit smoking 612 months prior). The denominator for this measure includes both current smokers who smoked for at least 2 years and former smokers who quit during the past year. The continuum included the proportion of current smokers who had ever tried to quit smoking, whether they had attempted to quit during the past year, and their current interest in quitting. It is important to note that in addition to excluding those who may have quit for 1 day during the past year, this measure does not include pastyear quit attempts of less than 1 day. Participants were asked, "Overall, on a scale from 1 to 10, where 1 is not at all interested and 10 is extremely interested, how interested are you in quitting smoking? This question was asked of current cigarette smokers who used another tobacco product or who used two or more tobacco products. Tobacco counseling refers to any information provided that related to tobacco use in any form, including cigarettes, cigars, snuff, and chewing tobacco, and on exposure to tobacco Patterns of Smoking Cessation Among U. Adults, Young Adults, and Youth 119 A Report of the Surgeon General in the form of secondhand smoke, smoking cessation, and prevention of tobacco use, as well as referrals to other healthcare providers for smoking cessation programs. Receipt of advice to quit was defined as having been given advice from a medical doctor, dentist, or other health professional to quit smoking or to quit using other kinds of tobacco among current cigarette smokers and former smokers who quit during the past year. A separate measure, being advised not to use tobacco, was defined using current cigarette smokers (smoked cigarettes during the 30 days preceding the survey) as being advised by a doctor, dentist, or nurse during the past 12 months not to use tobacco that is smoked or put in the mouth. Counseling is defined as having used one-on-one counseling; a stop-smoking clinic, class, or support group; and/or a telephone helpline or quitline during the past year, among current smokers who tried to quit in the past year and among former smokers who quit in the past 2 years. Current smokers were also asked if they did any of the following the last time they tried to quit: tried to quit by switching to (a) smokeless tobacco, such as chewing tobacco, snuff, or snus; (b) regular cigars, cigarillos, little filtered cigars, or any pipes filled with tobacco, and (c) electronic or e-cigarettes. Assessment of factors affecting the validity of self-reported health-risk behavior among adolescents: evidence from the scientific literature. The association of survey setting and mode with self-reported health risk behaviors among high school students. Methodologic changes in the Behavioral Risk Factor Surveillance System in 2011 and potential effects on prevalence estimates. The accuracy of self-reported smoking: a systematic review of the relationship between 1For self-reported and cotinine-assessed smoking status. Prevalence of youth substance use: the impact of methodological differences between two national surveys. An assessment of the effect of data collection setting on the prevalence of health risk behaviors among adolescents. Integrating smoking cessation into routine public prenatal care: the Smoking Cessation in Pregnancy project. Determinants of social desirability bias in sensitive surveys: a literature review. Monitoring the Future national survey results on drug use, 19752015: Volume I, Secondary school students. Adults, Young Adults, and Youth 121 A Report of the Surgeon General Ryan H, Trosclair A, Gfroerer J. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 1994. The biologic mechanisms underlying nicotine addiction continue to be a subject of great research interest, and several promising pharmacotherapeutic targets have emerged. This section describes the preclinical basis for understanding nicotine addiction and the ways that this knowledge could be used to enhance smoking cessation. Vaccines and other immunotherapies as treatments for tobacco addiction focuses on the conceptual basis of vaccine treatment, vaccine mechanistic design, and vaccine animal studies; progress made and barriers encountered with the early generation vaccines; and approaches to next-generation treatments and passive immunization. Insights into smoking cessation from the field of neurobiology describes the brain circuitry involved in nicotine dependence, as understood primarily through advances in brain imaging techniques; the role of stress, craving, and reward; and changes in cognitive control. Findings provide insight into the effects of smoking on the brain and the potential to identify new types of targets for smoking cessation. Genetic studies of smoking phenotypes focuses on the further mechanistic understanding gained from the interindividual differences that genetics creates and from some of the methodologic approaches that can be used to examine genetics in humans. Findings provide insight into distinct classes of genes that represent potential targets for novel smoking cessation therapeutics and optimizing choice of treatment. Cell and Molecular Biology of Nicotine Addiction Literature Review Methods For this section of the chapter, PubMed was searched in January 2017 for studies published between 2010 and 2017 that focused on the neurobiologic mechanisms underlying nicotine addiction in model organisms and in human subjects. These studies and a current search of clinical trials websites were used to identify molecular targets for the development of novel smoking cessation aids and ongoing clinical trials of relevant therapeutic agents. The cited references for preclinical work represent a compilation of the current knowledge base obtained from rodent studies, but the base cannot be considered completely comprehensive because of the large volume of studies in this area. Through these processes, nicotine stimulates the release of many different neurotransmitters throughout the brain. The reward associated with the release of dopamine is one of the underlying mechanisms of the development of nicotine dependence. In fact, the dopaminergic pathway is targeted by existing pharmacotherapies for smoking cessation. In humans, these receptors are assembled from combinations of 17 known subunits, 12 of which are expressed in the brain (210 and 24) (Picciotto et al. The 4 and 2 subunits, which are expressed throughout the brain and body in many types of cells, nearly always assemble together, sometimes with additional subunits, and their interface forms a high-affinity nicotine binding site (Kutlu and Gould 2016). Activation of these 4- and 2-containing receptors is required for many of the neurobiologic and behavioral effects associated with nicotine reward. The 6 subunit also can associate selectively with these receptors in dopamine and norepinephrine neurons (Kutlu and Gould 2016). Upon binding of either nicotine or acetylcholine, the receptors undergo a structural change that causes the ion channel to open, permitting the influx of cations and membrane depolarization. Nicotine also binds to intracellular receptors in the endoplasmic reticulum and promotes their assembly and trafficking. The extent of desensitization varies with the composition of receptors and concentration of nicotine. The variability in this balance also may contribute to individual differences in susceptibility to nicotine addiction. Notes: "Binge and intoxication" and "feeling euphoric" are not relevant to nicotine. During withdrawal, the activation of brain regions involved in emotions (in pink) results in negative mood and enhanced sensitivity to stress. During preoccupation, the decreased function of the prefrontal cortex leads to an inability to balance the strong desire for the drug with the will to abstain, which triggers relapse and reinitiates the cycle of addiction. The compromised neurocircuitry reflects the disruption of the dopamine and glutamate systems and the stress-control systems of the brain, which are affected by corticotropin-releasing factor and dynorphin. The behaviors during the three stages of addiction change as a person transitions from drug experimentation to addiction as a function of the progressive neuroadaptations that occur in the brain" (Volkow et al. New Biological Insights into Smoking Cessation 127 A Report of the Surgeon General Figure 3. The most common combinations are formed as homomers (all subunits the same) of the 7 subunit, or heteromers of the 4 and 2, or 3 and 4 subunits. Many subunit combinations with different properties are possible, with variability particularly at the fifth position in the receptor (indicated in grey as a choice of or subunit in this figure). Assembled receptors form a channel through the membrane, with a pore that is closed under resting conditions. Nicotine Withdrawal and Relapse Chronic nicotine use can induce a physical dependence severe enough that cessation induces a series of negative withdrawal symptoms in humans and in laboratory animals (Picciotto et al. Thus, 128 Chapter 3 Smoking Cessation in addition to being drawn to the primary reinforcing properties of nicotine, many persons return to smoking to avoid negative effects of abstinence, such as irritability, anxiety, depression, insomnia, and difficulty concentrating. For example, former smokers who used to have a cigarette with their morning coffee may experience intense nicotine cravings at the smell of coffee, which could trigger relapse to smoking (Bevins and Palmatier 2004). Importantly, drug-paired cues (things in the environment that are associated with nicotine being on board) can become themselves reinforcing after repeated pairings, and this conditioned reinforcement may be at least partially responsible for continuing drug use and relapse. Mechanistically, perseverative drug use and high relapse rates happen because of persistent neurobiologic adaptations (tolerance), particularly within the mesocorticolimbic dopamine system. For this reason, several research efforts have focused on elucidating the neurobiologic underpinnings of relapse. Animal Models of Nicotine Addiction Studies of animal models of disease have contributed to much of our understanding of the neurobiologic basis of nicotine addiction. Although animal models cannot capture the full range of human addiction, mice and rats do develop addiction-like behaviors, and several reliable paradigms have been established to measure specific aspects of the disease in animals. The drugs that animals self-administer correspond well with drugs that have high abuse liability in humans (Carter and Griffiths 2009). As described in detail below, nicotine-dependent animals will work to obtain nicotine and to relieve nicotine withdrawal symptoms (Koob and Simon 2009). Therefore, animal models are useful for measuring the abuse liability of addictive drugs, such as nicotine, and identifying pharmacotherapies that make addictive drugs less reinforcing or that mitigate withdrawal symptoms. Over time, the animal learns to associate the context with nicotine and develops a preference for that environment over an adjacent, similar environment that is not paired with nicotine. The development of such a preference is considered to be an indication of the rewarding effects of the drug. In the self-administration model, animals are trained to complete an operant task, such as pressing a lever to receive an infusion of nicotine. Once the task is learned, changes in operant behavior are thought to indicate changes in drug reinforcement or craving. Interestingly, self-administration of nicotine is more robust if infusion is paired with a cue versus with the drug alone (Caggiula et al. Modeling Nicotine Withdrawal and Relapse Human smokers often relapse in response to one of three stimuli: exposure to environmental cues associated with nicotine, aversive or stressful life events, or a small amount of the drug. Each of these types of stimuli is also sufficient to induce reinstatement of nicotine-seeking behavior in rodents after forced extinction of the behavior. In the cue-induced reinstatement model, animals are trained to self-administer nicotine that is paired with an innocuous cue, such as a light or a tone. After self-administration of nicotine is acquired, the operant behavior can be extinguished by placing the animals in the same context but in the absence of the drug and the associated cue. Following extinction, animals will resume responding to the cue alone, even in the absence of nicotine. Similar paradigms have been developed to model stress-induced reinstatement and drug-induced reinstatement in animals, all of which may be valid for nicotine relapse in humans (Mantsch et al. Preclinical studies using these paradigms have been useful in identifying cellular and molecular processes that contribute to drug reinstatement, as discussed in this section. Molecular Targets of Current Pharmacotherapies As a consequence of our understanding of the neurobiology of nicotine addiction, several successful pharmacotherapies have been developed to aid in smoking cessation (Table 3. Repeated efficacy studies, including a Phase 3 clinical trial in New Zealand, have found cytisine to be effective for smoking cessation at levels similar to varenicline (Etter 2006). Because cytisine is a naturally occurring compound, it is less expensive than currently available cessation aids, making it a potentially promising tool for reducing smoking rates in certain populations, including low-income individuals. With withdrawal-induced negative affect a major problem for smokers trying to quit, antidepressants are often prescribed, and several of these drugs have shown efficacy 130 Chapter 3 Smoking Cessation in reducing smoking (Hughes et al. Bupropion can alleviate withdrawal symptoms and reduce the severity of nicotine cravings. Regardless, glutamatergic signaling in mesocorticolimbic regions clearly contributes to nicotine reinforcement. Gipson and colleagues (2013) demonstrated that long-lasting changes in glutamate signaling are central to post-withdrawal reinstatement of nicotine-seeking behavior in rats. Similar observations have been made with other drugs of abuse, such as cocaine and alcohol. Although blockade of ionotropic glutamate receptors is effective in reducing addiction-like behaviors in animal models, systemic use of these drugs in humans is likely not feasible using current pharmacologic agents, given the crucial role of glutamate in the function of the nervous system. Also, because glutamate plays different roles in different regions of the brain, a more targeted, region-specific approach is warranted. Metabotropic Glutamate Receptors Metabotropic glutamate receptors (mGluRs) are widely expressed, G-protein-coupled receptors that use second-messenger systems (key distributors of an external signal) to modulate neuronal excitability. Two of these receptors, mGluR5 and mGluR2, have been implicated in Novel Targets for Smoking Cessation Glutamatergic Signaling Although enhanced dopamine signaling is critical for the initial reinforcing properties of nicotine, both the maintenance and reinstatement of nicotine-seeking behavior require long-lasting alterations in the actions of glutamate, the major excitatory neurotransmitter in the brain (Knackstedt and Kalivas 2009; Li et al. Repeated exposure to nicotine results in a long-term potentiation (or long-lasting increase in activation) of these synapses, which contributes to elevated excitability of dopamine neurons. Thus, chronic use of nicotine causes long-lasting changes to the mesolimbic dopamine system, many of which are driven by alterations in glutamate transmission. Behaviorally, these adaptations sustain drug cravings and contribute to a vulnerability to relapse. Glutamate binds to and activates two types of receptors: ionotropic, which are ion channels that allow current to pass through and activate cell membranes; and metabotropic, which are G-proteincoupled receptors that activate downstream cell signaling cascades. Neuroadaptive mechanisms in the glutamate system, perhaps on both types of glutamate receptors, may be targets for pharmacologic intervention. New Biological Insights into Smoking Cessation 131 A Report of the Surgeon General the neurobiology of nicotine addiction. Additionally, both drug- and cueinduced reinstatement of nicotine-seeking behavior are reduced in animals that have been pretreated with mGluR5 antagonists (Bespalov et al. In humans, studies using selective mGluR5 radiotracers have revealed a significant reduction of binding sites in the brains of persons addicted to nicotine, which is normalized after cessation (Akkus et al. The mechanism for this reduction is not entirely understood, but it may be a compensatory action meant to limit aberrant glutamate signaling in the brains of smokers. Although the curbing of appetite during smoking cessation may seem like an appealing side effect, such overly generalized effects may be dangerous or undesirable. In contrast to mGluR5, mGluR2 is expressed on presynaptic glutamate terminals, acting as an autoreceptor that inhibits the release of this neurotransmitter. A Phase 2 clinical trial of this drug for smoking cessation was completed in January 2017, but results are not yet available. This study enrolled 210 female cigarette smokers and evaluated abstinence from nicotine as a primary endpoint. Although GluR5 and GluR2 have been linked to addiction-like behaviors in animals, Acri and colleagues (2017) argued that mGluR2 may be a more feasible drug target because of its relatively mild side-effect profile compared with mGluR5 antagonists. Glutamate Transporters Alterations in the function of glutamate transporters also contribute to nicotine-mediated disruptions in the excitatoryinhibitory balance.
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Each A band is interrupted in the midsection by an H zone (from the German Hellerscheibe antimicrobial scrubs purchase 3 mg ivermectin amex, for "clear disc") virus 404 error buy 3mg ivermectin otc, where there is no overlap of thick and thin filaments antibiotic kidney stones ivermectin 3 mg online. Running through the center of the H zone is a dense line called the M line (from the German Mittelsclzeibe antibiotics for uti amoxicillin dosage order ivermectin 3mg overnight delivery, for "middle disc") antibiotics for uti how long does it take to work order ivermectin 3 mg without a prescription. The I bands are also interrupted at the midline by a darker area called the Z disc (from the German Zwischenscheibe 7daystodie infection cheap 3 mg ivermectin with amex, for "between disc") virus b cheap ivermectin 3 mg online. The arrangement of the myofilaments at different points in the sarcomere is shown in Figure 2-5 antibiotics for sinus infection safe during pregnancy buy generic ivermectin 3mg line, D and F. Notice that in regions where the thick and thin filaments overlap, each thick filament is Chapter 2 Understanding Muscle Contraction Sarcolemma Mitochondrion Myofilaments 19 Myofibrils Z disc I band A band Z disc I band Muscle fiber T tubules Nuclei Sarcoplasmic reticulum Z disc Sarcomere Z disc Thick filament Thin filament Troponin complex Actin Tropomyosin Myosin Figure 2-4 Organization of a muscle fiber. A close anatomical relationship exists among the organelles, specifically the myofibrils, T tubules, and sarcoplasmic reticulum. The repeating pattern of the myofibrils is due to the arrangement of the myofilaments. Proteins of the cytoskeleton provide much of the internal structure of the muscle cell. Figure 2-6 diagrams the cytoskeleton of the sarcomere and its relationship to the contractile proteins. The elastic filament helps keep the thick filament in the middle between the two Z discs during contraction. The globular myosin heads extend outward and form cross-bridges when they interact with thin filaments. Only when the myosin heads bind to the active sites on actin, forming a cross-bridge, does contraction occur. The myosin subunits are oriented in opposite directions along the filament, forming a central section that lacks projecting heads (Figure 2-7, C). The result is a bare zone in the middle of the filament, which accounts for the H zone seen in the middle of the A band (Figure 2-7, D). A Sarcomere Thin Filaments Thin filaments are composed primarily of the contractile protein actin. As illustrated in Figures 2-8, A and B, actin is composed of small globular subunits (G actin) that form long strands called fibrous actin (F actin). A filament of actin is formed by two strands of F actin coiled about each other to form a double helical structure; it resembles two strands of pearls wound around each other and may be referred to as a coiled coil (Figure 2-8, C). The actin molecules contain active sites to which myosin heads will bind during contraction. The thin filaments also contain the regulatory proteins called tropomyosin and troponin, which regulate the interaction of actin and myosin. Tropomyosin is a long, double-stranded, helical protein that is wrapped about the long axis of the actin backbone (Figure 2-8, D). Tropomyosin serves to block the active site on actin, thereby inhibiting actin and myosin from binding under resting conditions. Troponin is a small, globular protein complex composed of three subunits that control the position of the tropomyosin (Figure 2-9). The three units of troponin are troponin C (Tn-C), troponin I (Tn-I), and troponin T (Tn-T). Tn-C contains the calcium-binding sites, Tn-T binds troponin to tropomyosin, and Tn-I inhibits the binding of actin and myosin in the resting state (Figure 2-9, B). When calcium binds to the Tn-C subunit, the troponin complex undergoes a configurational change. Because troponin is attached to tropomyosin, the change in the shape of troponin causes tropomyosin to be removed from its blocking position, thus exposing the active sites on actin. Thus calcium is the key to controlling the interaction of the filaments and therefore muscle contraction. B Z disc H zone Z disc M line C Thin filament A band I band Thick filament Thin filament Thick filament Thick and thin filament D E F Figure 2-5 Arrangement of myofilaments in a sarcomere. Therefore paying careful attention to the structure of the myofilaments is essential. Thick Filaments Thick filaments are composed primarily of myosin molecules (Figure 2-7). Each molecule of myosin has a rodlike tail and two globular heads (Figure 2-7, A). The message from the motor neuron must then be passed to the muscle fiber through the neuromuscular junction. The process whereby electrical events in the Chapter 2 Understanding Muscle Contraction Thin filament: actin, troponin, tropomyosin Thick filament: myosin 21 Connections between two sarcomeres from adjacent myofibrils: desmin Z line (Z disc): actinin Nebulin M line M protein Myomesin M creatine kinase C stripes C protein X protein H protein Elastic filaments: titin Figure 2-6 Representation of auxiliary proteins in the sarcomere. The Sliding-Filament Theory of Muscle Contraction B C Tail Thin filament Thick filament D Z disc A great deal of data has been amassed since the 1950s on the basis of x-ray, light microscopic, and electron microscopic studies to support the sliding-filament theory of muscle contraction. The force of contraction is generated by the process that slides the actin filament over the myosin filament. The lengths of the thick and the thin filaments do not change during muscle contraction. The length of the sarcomere decreases as the actin filaments slide over the myosin filaments and pull the Z discs toward the center of the sarcomere. The generation of force Sarcomere Z disc Figure 2-7 Molecular organization of thick filaments. B, Individual molecules are arranged so that the tails form a rodlike structure and the globular heads project outward to form crossbridges. C, Myosin subunits are oriented in opposite directions along the filament, forming a central bare zone in the middle of the filament (H zone). D, Thick filament (myosin) within a single sarcomere showing the myosin heads extending toward the thin filament. When calcium is released from the sarcoplasmic reticulum (the second phase), it binds to the troponin molecules on the thin filament. The binding of calcium to troponin causes 22 Sports-Specific Rehabilitation (A) G actin Active site (B) F actin (C) Actin filament (D) Tropomyosin (E) Troponin (F) Thin filament Troponin I Troponin T Troponin C Figure 2-8 Molecular organization of thin filaments. A, Individual actin subunits (globular, G actin) shown with active site for binding to myosin heads. C, Actin filament with two strands of fibrous actin wound around itself to form a coiled coil. E, Troponin is a regulatory protein that, when bound to Ca2++, removes tropomyosin from its blocking position on actin. The third phase of excitation-contraction coupling is the cross-bridging cycle (point 5 in Figure 2-10). The cross-bridging cycle describes the cyclic events that are necessary for the generation of force or tension within the myosin heads during muscle contraction. The generation of tension within the contractile elements results from the binding of the myosin heads to actin and the subsequent release of stored energy in the myosin heads. As shown in Figure 2-11, four individual steps are necessary for the crossbridging cycle3,4,7: 1. Activation of myosin heads the first step in the cross-bridge cycle is the binding of activated myosin heads (*M) with the active sites on actin, forming cross-bridges. In Figure 2-11 a centered dot (·) is used to indicate binding, and an asterisk (*) is used to indicate activated myosin heads. Thus A·*M indicates that the activated A B TnT TnI TnC Tropomyosin Actin Figure 2-9 Regulatory function of troponin and tropomyosin. B, Resting condition: Tropomyosin blocks the active sites on actin, preventing actin and myosin from binding. C, Contraction: When troponin binds with Ca2+, it undergoes a configurational change and pulls tropomyosin from the blocking position on the actin filament, following myosin heads to form cross-bridges with actin. During this step, activated myosin heads swivel from their high-energy, activated position to a low-energy configuration (M with no *). This movement of the myosin crossbridges results in a slight displacement (sliding) of the thin filament over the thick filament toward the center of the sarcomere. Activation of the myosin heads is extremely important because it provides the cross-bridges with stored energy to move the actin during the power stroke. On the other hand, activated myosin remains in the resting state awaiting the next stimulus if calcium is not available in sufficient concentration to remove tropomyosin from its blocking position on actin (see step 4b in Figure 2-11). Because each cycle of the myosin cross-bridges barely displaces the actin, the myosin heads must bind to the actin and be displaced many times for a single contraction to occur. Thus myosin makes and breaks its bond with actin hundreds or even thousands of times during a single muscle twitch. In order for this make-and-break cycle to occur, myosin heads must detach from actin and then be reactivated. In a similar manner, the myosin head possesses stored energy, which is released when the myosin heads bind to actin and swivel. The final phase of muscular contraction is muscular relaxation (see point 6 in Figure 2-10 and step 4b in Figure 2-11). Relaxation occurs when the nerve impulse ceases and calcium is pumped back into the sarcoplasmic reticulum by active transport. In the absence of calcium, tropomyosin returns to its blocking position on actin, and myosin heads are not able to bind to actin. Although emphasis is often placed on muscle contraction, the ability to relax a muscle following contraction is just as important. Changes in the Sarcomere during Contraction Much of the evidence supporting the sliding-filament theory comes from observation of changes in the length of a sarcomere during muscular contraction. Diagrams of the sarcomere during rest and during contraction are shown in Figure 2-12, A and Figure 2-12, B, respectively. B, During contraction of the sarcomere, the lengths of actin and myosin filaments are unchanged. Sarcomere shortens because actin slides over myosin, pulling Z discs toward the center of the sarcomere. The I band shortens because the thin filaments are pulled over the thick filaments toward the center of the sarcomere. Thus there is little or no area where the thin filaments do not overlap the thick filaments. The H zone shortens and may disappear because the thin filaments are pulled over the thick filaments toward the center of the sarcomere. If the thin filament overlaps the thick filament for the entire length of the thick filament, there is no H zone. The shortening of the sarcomere is the result of the attachment of the myosin heads with the active site on actin and the subsequent release of stored energy that swivels the myosin crossbridges. This step causes the actin to pull the Z disc toward the center of the sarcomere, which, in turn, causes the sarcomere and hence the muscle fiber length to decrease. All-or-None Principle According to the all-or-none principle, when a motor neuron is stimulated, all of the muscle fibers in that motor unit contract to their fullest extent or they do not contract at all. The minimal amount of stimuli necessary to initiate that contraction is referred to as the threshold stimulus; that is, if the threshold of contraction is reached, a muscle fiber will contract to its fullest extent. This phenomenon is related to the electrical properties of the cell membrane and refers to the contractile properties of a motor unit or a single muscle fiber only, not to the entire muscle. If sufficient pressure is applied to the switch (to reach a threshold for flipping it on), the lights are turned on to their fullest extent. Expanding the analogy to a motor unit, when a light switch that controls a group of lights (such as the overhead lights in a classroom) is turned on, all of the lights connected to it will turn on to their fullest extent. The lights do not become brighter if the light switch is pulled (or pushed) harder. The same is true for an individual muscle fiber or a motor unit: Either a threshold stimulus is reached and contraction occurs, or a threshold stimulus is not reached and contraction does not occur. Muscle Fiber Types Muscle fibers are typically described by two characteristics: their contractile, or twitch, properties and their metabolic properties (Figure 2-13). Metabolic Properties On the basis of differences in metabolic properties, human muscle fibers can be described as glycolytic, oxidative, or a combination of both, oxidative/glycolytic. Despite the ability of all muscle fibers to produce energy by both glycolytic and oxidative processes, one or the other may predominate or the production may be balanced. Thus the metabolic properties of muscle fibers do not represent discrete entities as much as a continuum (oxidative to glycolytic), or shades of gray, as opposed to the black-and-white type of dichotomy seen for twitch speed (slow or fast twitch). As described previously, the twitch speed of a muscle fiber depends largely on the motor neuron that innervates it. In addition, because all muscle fibers in a motor unit are recruited to contract together, they will require the same metabolic capabilities as well. Thus when reference is made to muscle fiber types, it also means motor unit types. To understand the difference between twitch speeds, the integration of muscles and nerves must be considered. Skeletal muscle fibers are innervated by alpha motor neurons, which are subdivided into two categories, 1 and 2. The size difference is important because small motor neurons have low excitation thresholds and slow conduction velocities and are thus recruited at low workloads. In contrast, larger motor neurons have a higher excitation threshold and are not recruited until high force output is necessary. B, If the neurons supplying the muscles are switched (cross-innervated), the muscle fibers acquire the properties of the new motor neuron. The size of the muscle fiber is related to the size of the nerve fiber innervating it but primarily reflects the amount of contractile proteins within the muscle cell. Figure 2-15 indicates differences in force production, twitch speed, and fatigue curves for the three types of muscle fibers. The metabolic differences among muscle fibers both require and reflect differences in energy substrate availability. Fiber type differences help explain individual differences in performance and response to training. The relationship among fiber types, training, and performance in elite athletes helps in the design of training programs for others who wish to be successful in specific events even if they do not know their exact fiber type percentages or distribution. Distribution of Fiber Types All of the muscles of the human body are composed of a combination of slow-twitch and fast-twitch muscle fibers arranged in a mosaic pattern. This arrangement is thought to reflect the variety of tasks that human muscles must perform. The relative distribution, or percentage, of these fibers, however, may vary greatly from one muscle to another. The distribution may also vary considerably from one individual to another for the same muscle group. The distribution of fiber types is not different for males and females, although males tend to show greater extremes or variation than females. After early childhood the fiber distribution does not change significantly as a function of age. Assessment of Muscle Fiber Type Muscle fiber type is typically determined by an invasive procedure that involves collecting a small sample of skeletal muscle by a needle biopsy (Figure 2-16). Muscle biopsies are most commonly obtained from the gastrocnemius, vastus lateralis, or deltoid muscles. Before the collection of the muscle sample, the skin is thoroughly cleaned and a topical anesthetic is applied to numb the area. The biopsy needle is then inserted into the belly of the muscle to extract a small amount of skeletal muscle tissue (20 to 40 mg). The small sample of muscle is frozen in liquid nitrogen and sliced into thin crosssections. The cross-sections are then chemically stained so that the muscle fibers can be differentiated into categories. When the stained muscle fibers are viewed in cross-section under a microscope, the muscle fiber types appear a different color. Notice that the different fiber types are intermingled, revealing a mosaic pattern. Counting the number of fibers of each category and dividing by the total number of fibers seen will indicate a percentage of each fiber type. In addition to counting the number of fibers and expressing them as a percentage, researchers often measure the diameter of the muscle fibers. However, a large range of fiber type exists in each group, indicating that athletic success is not determined solely by fiber type. Not only do endurance athletes differ in general fiber type from power or resistance athletes, but often these differences are site specific within athletic groups. An interesting question arises when looking at the fiber type distribution of various athletes: Did training for and participating in a given sport influence the fiber type, or did fiber type influence the type of athletic participation? The neurons that carry information from the central nervous system to the muscle are called efferent neurons. Efferent neurons that innervate skeletal muscles are referred to as motor neurons. Motor neurons may be classified as alpha motor neurons or gamma motor neurons. Alpha motor neurons are relatively large motor neurons that innervate skeletal muscle fibers and result in contraction of muscles. As a nerve enters the connective tissue of the muscle, it divides into branches, with each branch ending near the surface of a muscle fiber. Because the axon of the motor neuron branches, each neuron is connected to several muscle fibers. A motor neuron and the muscle fibers it innervates is called a motor unit (Figure 2-20). Because each muscle fiber in a motor unit is connected to the same neuron, the electrical activity in that neuron controls the contractile activity of all the muscle fibers in that motor unit. Although a single neuron may innervate Percent of slow-twitch fibers 70 60 50 40 30 20 10 0 Percent of slow-twitch fibers Males Females 80 70 60 50 40 30 20 10 0 Vastus lateralis Deltoid High Cyclists Untrained Sprinters Middledistance jumpers runners Figure 2-18 Fiber distribution among athletes.
The two most common barriers to seeking treatment for a substance use disorder that lawyers reported were not wanting others to find out they needed help and concerns regarding privacy or confidentiality the infection 0 origins movie buy ivermectin 3mg on line. Top concerns of law students in the Survey of Law Student Well Being were fear of jeopardizing their academic standing or admission to the practice of law bacteria labeled buy 3mg ivermectin mastercard, social stigma antibiotics over the counter buy ivermectin 3 mg without prescription, and privacy concerns antimicrobial agents and chemotherapy abbreviation generic ivermectin 3 mg amex. The result of these barriers is that virus questions discount 3mg ivermectin otc, rather than seeking help early bacterial diseases purchase ivermectin 3mg otc, many wait until their symptoms are so severe that they interfere with daily functioning infection 4 months after c section generic ivermectin 3mg without prescription. Removing these barriers requires education antimicrobial keyboard covers 3 mg ivermectin free shipping, skillbuilding, and stigma-reduction strategies. Research shows that the most effective way to reduce stigma is through direct contact with someone who has personally experienced a relevant disorder. Ideally, this person should be a practicing lawyer or law student (depending on the audience) in order to create a personal connection that lends credibility and combats stigma. Because many soldiers (like many lawyers) perceive seeking help as a weakness, the campaign also has sought to re-frame help-seeking as a sign of strength that is important to resilience. Castro, Perceived Stigma and Barriers to Care for Psychological Treatment: Implications for Reactions to Stressors in Different Contexts, 27 J. Shaw, Attitudes and Factors Related to Seeking Mental Health Treatment among Medical and Dental Students, 14 J. Lee, How Are Perceived Stigma, Self-Stigma, and Self-Reliance Related to Treatment-Seeking? Many cover a range of well-being-related topics including substance use and mental health disorders, as well as cognitive impairment, process addictions, burnout, and chronic stress. Judges, regulators, legal employers, law schools, and bar associations should ally themselves with lawyer assistance programs to provide the above services. These stakeholders should also promote the services of state lawyer assistance programs. They also should emphasize the confidential nature of those services to reduce barriers to seeking help. Lawyers are reluctant to seek help for mental health and substance use disorders for fear that doing so might negatively affect their licenses and lead to stigma or judgment of peers. We also recommend coordinating regular meetings with lawyer assistance program directors to create solutions to the problems facing the profession. Lawyer assistance programs can help organizations establish confidential support groups, wellness days, trainings, summits, and/ or fairs. We also recommend partnerships with lawyer wellbeing committees and other types of organizations and consultants that specialize in relevant topics. A number of state bars also have well-being committees including Georgia, Indiana, Maryland, South Carolina, and Tennessee. We recommend that all stakeholders develop and enforce standards of collegiality and respectful engagement. Judges, regulators, practicing lawyers, law students, and professors continually interact with each other, clients, opposing parties, staff, and many others. It depletes energy and motivation, increases burnout, and inflicts emotional and physiological damage. For example, in a 1992 study, 42 percent of lawyers and 45 percent of judges believed that civility and professionalism among bar members were significant problems. In a 2007 survey of Illinois lawyers, 72 percent of respondents categorized incivility as a serious or moderately serious problem33 in the profession. A recent study of over 6,000 lawyers found that lawyers did not generally have a positive view of lawyer or judge professionalism. As a start, we recommend that bar associations and courts adopt rules of professionalism and civility, such as those that exist in many jurisdictions. This should include an expectation that all leaders in the profession be a role model for these standards of professionalism. Research reflects that organizational diversity and inclusion initiatives are associated with employee well-being, including, for example, general mental and physical health, perceived stress level, job satisfaction, organizational commitment, trust, work engagement, See C. Lawrence, Incentivizing Lawyers to Play Nice: A National Survey on Civility Standards and Options for Enforcement, 48 U. Porath, On the Nature, Consequences and Remedies of Workplace Incivility: No Time for "Nice"? Gallus, Assessing Workgroup Norms for Civility: the Development of the Civility Norms Questionnaire-Brief, 27 J. Magley, Selective Incivility as Modern Discrimination in Organizations: Evidence and Impact, 30 J. Given the above, we recommend that all stakeholders urgently prioritize diversity and inclusion. Regulators and bar associations can play an especially influential role in advocating for initiatives in the profession as a whole and educating on why those initiatives are important to individual and institutional well-being. Another relevant initiative that fosters inclusiveness and respectful engagement is mentoring. Research has shown that mentorship and sponsorship can aid wellbeing and career progression for women and diverse professionals. Practices that rob lawyers of a sense of autonomy and control over their schedules and lives are especially harmful to their well-being. Research studies show that high job demands paired with a lack of a sense of control breeds depression and other psychological disorders. Obst, Depression and Belongingness in General and Workplace Contexts: A Cross-Lagged Longitudinal Investigation, 33 J. Wiethoff, the Interactive Effects of Gender and Mentoring on Career Attainment: Making the Case for Female Lawyers, 37 J. Marmot, the Importance of Low Control at Work and Home on Depression and Anxiety: Do these Effects Vary by Gender and Social Class? Achor, Rethinking Stress: the Role of Mindsets in Determining the Stress Response, 10 J. All stakeholders should ensure that legal professionals receive training in identifying, addressing, and supporting fellow professionals with mental health and substance use disorders. Some evidence reflects that social norms predict problem drinking even more so than stress. A more comprehensive, systemic campaign is likely to be the most effective-though certainly the most challenging. To alleviate resistance based on such concerns, prevention programs should consider making "it clear that they are not a temperance movement, only a force for moderation," and that they are not designed to eliminate bonding but to ensure that drinking does not reach damaging dimensions. Efforts aimed at remodeling institutional and organizational features that breed stress are 9. Like the general population, the lawyer community is aging and lawyers are practicing longer. At the same time, however, aging lawyers have an increasing risk for declining physical and mental capacity. Yet few lawyers and legal organizations have sufficiently prepared to manage transitions away from the practice of law before a crisis occurs. The result is a rise in regulatory and other issues relating to the impairment of senior lawyers. We make the following recommendations to address these issues: Well-being efforts must extend beyond detection and treatment and address root causes of poor health. All stakeholders should participate in the development and delivery of educational materials and programming that go beyond detection to include causes and consequences of distress. Appendix B to this report offers examples of well-being-related educational content, along with empirical evidence to support each example. Create transition programs to respectfully aid retiring professionals plan for their next chapter. McNickle, A Grounded Theory Study of Intrinsic Work Motivation Factors Influencing Public Utility Employees Aged 55 and Older as Related to Retirement Decisions (2009) (doctoral dissertation, Capella University) (available from ProQuest Dissertations and Theses Database). Second, judges, legal employers, bar associations, and regulators should develop succession plans, or provide education on how to do so, to guide the transition of aging legal professionals. Programs should include help for aging members who show signs of diminished cognitive skills, to maintain their dignity while also assuring they are competent to practice. Lawyers whose self-esteem is contingent on their workplace success are likely to delay transitioning and have a hard time adjusting to retirement. On the other hand, social norms can also lead colleagues to encourage those who abuse alcohol to seek help. The expectation of drinking is embedded in the culture, which may contribute to over-consumption. Legal employers, law schools, bar associations, and other stakeholders that plan social events should provide a variety of alternative non-alcoholic beverages and consider other types of activities to promote socializing and networking. They should strive to develop social norms in which lawyers discourage heavy drinking and encourage others to seek help for problem use. Extensive research has demonstrated that random drug and alcohol testing (or "monitoring") is an effective way of supporting recovery from substance use disorders and increasing abstinence rates. The medical profession has long relied on monitoring as a key component of its treatment paradigm for physicians, resulting in longterm recovery rates for that population that are between 70-96 percent, which is the highest in all of the treatment outcome literature. Workplace cultures or social climates that support alcohol consumption are among the most consistent predictors of employee drinking. Koestner, the Role of Passion for Work and Need for Satisfaction in Psychological Adjustment to Retirement, 88 J. Gold, Setting the Standard for Recovery: Physicians Health Programs Evaluation Review, 36 J. Shore, the Oregon Experience with Impaired Physicians on Probation: An Eight Year Follow-Up, 257 J. Although the benefits of monitoring have been recognized by various bar associations, lawyer assistance programs, and employers throughout the legal profession, a uniform or "best practices" approach to the treatment and recovery management of lawyers has been lacking. Through advances in monitoring technologies, random drug and alcohol testing can now be administered with greater accuracy and reliability-as well as less cost and inconvenience- than ever before. Law schools, legal employers, regulators, and lawyer assistance programs would all benefit from greater utilization of monitoring to support individuals recovering from substance use disorders. One model for this is through a "Call to Action," where members of the legal community and stakeholders from lawyer assistance programs, the judiciary, law firms, law schools, and bar associations are invited to attend a presentation and community discussion about the issue. When people who have been affected by the suicide of a friend or colleague share their stories, other members of the legal community begin to better understand the impact and need for prevention. Suicide, like mental health or substance use disorders, is a highly stigmatized topic. While it is an issue that touches many of us, most people are uncomfortable discussing suicide. Therefore, stakeholders must make a concerted effort towards suicide prevention to demonstrate to the legal community that we are not R. If you or someone you know is experiencing suicidal thinking, please seek help immediately. The National Suicide Prevention Lifeline can be reached at 1-800-273-8255, suicidepreventionlifeline. Stakeholders can contact their state lawyer assistance programs, employee assistance program agencies, or health centers at law schools to find speakers, or referrals for counselors or therapists so that resources are available for family members of lawyers, judges, and law students who have taken their own life. For law firms, it also may help counterbalance the "profits per partner metric" that has been published by the American Lawyer since the late 1980s, and which some argue has driven the profession away from its core values. Judges presiding over domestic relations dockets make life-changing decisions for children and families daily. A number take the bench with little preparation, compounding the sense of going it alone. We further recognize that many judges have the same reticence in seeking help out of the same fear of embarrassment and occupational repercussions that lawyers have. The public nature of the bench often heightens the sense of peril in coming forward. In light of these barriers and the stressors inherent in the unique role judges occupy in the legal system, we make the following recommendations to enhance well-being among members of the judiciary. The highest court in each state should set the tone for the importance of the well-being of judges. Judges are not immune from suffering from the same stressors as lawyers, and additional stressors are unique to work as a jurist. Miller, Evidence of Secondary Traumatic Stress, Safety Concerns, and Burnout Among a Homogeneous Group of Judges in a Single Jurisdiction, 37 J. It is essential that the highest court and its commission on judicial conduct implement policies and procedures for intervening with impaired members of the judiciary. For example, the highest court should consider adoption of policies such as a Diversion Rule for Judges in appropriate cases. Administrative and chief judges also should implement policies and procedures for intervening with members of the judiciary who are impaired in compliance with Model Rule of Judicial Conduct 2. They should feel comfortable referring members to judicial or lawyer assistance programs. Educating judicial leaders about the confidential nature of these programs will go a long way in this regard. Judicial associations should invite lawyer assistance program directors and other well-being experts to judicial conferences who can provide programming on topics related to self-care as well as resources available to members of the judiciary experiencing mental health or 16. As reflected in Recommendation 4, the stigma surrounding mental health and substance use disorders poses an obstacle to treatment. We recommend they work to reduce this stigma by creating opportunities for open dialogue. Simply talking about these issues helps combat the unease and discomfort that causes the issues to remain unresolved. In a similar vein, we encourage judges to participate in the activities of lawyer assistance programs, such as volunteering as speakers and serving as board members. Topics could include burnout, secondary traumatic stress, compassion fatigue, strategies to maintain well-being, as well as identification of and intervention for mental health and substance use disorders. Judicial educators also should make use of programming that allows judges to engage in mutual support and sharing of self-care strategies. One such example is roundtable discussions held as part of judicial conferences or establishing a facilitated mentoring 17. This report was triggered in part by the Study and the Survey of Law Student Well-Being. We have identified isolation as a significant challenge for many members of the judiciary. Roundtable discussions and mentoring programs combat the detrimental effects of this isolation. For example, a judicial association could create wellness guides such as "A Wellness Guide for Judges of the California State Courts. Judges, for example, can devote a bench-bar luncheon at the courthouse to well-being and invite representatives of the lawyers assistance program to the luncheon. Judicial educators should include a section in bench book-style publications dedicated to lawyer assistance programs and their resources, as well as discussing how to identify and handle lawyers who appear to have mental health or substance use disorders. Further, judges and their staff should learn the signs of mental health and substance use disorders, as well as strategies for intervention, to assist lawyers in their courtrooms who may be struggling with these issues. Judges can also advance the well-being of lawyers who appear before them by maintaining courtroom decorum and deescalating the hostilities that litigation often breeds. Judges know when a lawyer is late to court regularly, fails to appear, or appears in court under the influence of alcohol or drugs. They witness incomprehensible pleadings or cascading requests for extensions of time. We make the following recommendations tailored to helping judges help the lawyers appearing before them. They should understand the confidentiality protections surrounding these referrals. Judges also should invite lawyer assistance programs to conduct educational programming for lawyers in their jurisdiction using their courtroom or other courthouse space. We broadly define "regulators" to encompass all stakeholders who assist the highest court in each state in regulating the practice of law. Courts and their regulators frequently witness the conditions that generate toxic professional environments, the impairments that may result, and the negative professional consequences for those who do not seek help. Regulators are well-positioned to improve and adjust the regulatory process to address the conditions that produce these effects. As a result, we propose that the highest court in each state set an agenda for action and send a clear message to all participants in the legal system that lawyer well-being is a high priority. Regulators can transform this perception by building their identity as partners with the rest of the legal community rather than being viewed only as its "police. Accordingly, we offer the following recommendations to ensure that the regulatory process proactively fosters a healthy legal community and provides resources to rehabilitate impaired lawyers. To carry out the agenda, regulators should develop their reputation as partners with practitioners. In doing so, it recommended proactive programs offered by the Colorado Lawyer Assistance Program and other organizations to assist lawyers throughout all stages of their careers to practice successfully and serve their clients. Such objectives will send a clear message that the court prioritizes lawyer well-being, which influences competent legal services. The goal of the proposed amendment is not to threaten lawyers with discipline for poor health but to underscore the importance of wellbeing in client representations. It is intended to remind lawyers that their mental and physical health impacts clients and the administration of justice, to reduce stigma associated with mental health disorders, and to encourage preventive strategies and self-care. California and Illinois are examples of state bars that already have such requirements. Notably, we do not recommend discipline solely for a 96 97 Washington Courts, Suggested Amendments to General Rules (2017). Tennessee is one example of a pioneering state that authorizes credit for a broad set of well-being topics. Require Law Schools to Create Well-Being Education for Students as An Accreditation Requirement.
