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One such effort discussed was Sierra Valley Cancer Registry Services, which is a registry that collects self-reported information related to exposures and confirmed diagnosis of glioblastoma for Vietnam veterans. As of 2017, the registry contains information on 372 Vietnam veterans who have been diagnosed with glioblastoma. This correlation was confirmed in a further study of 14 human neuroblastoma samples. Synthesis Studies of Vietnam veterans have not found statistically significant associations between deployment and presumed exposure to the herbicides and incidence or mortality of brain or other nervous system cancers. However, the study lacked exposure estimates and was underpowered and potentially biased by missing data, and, ultimately, the committee considered it an exploratory analysis and did not give it full weight. Given the limited epidemiologic data available on glioblastoma, the committee heard invited presentations from two glioblastoma experts. Papillary carcinoma is the most common and accounts for the majority of the increasing incidence rate (Lubitz and Sosa, 2016). Follicular carcinoma (or follicular adenocarcinoma), which is associated with inadequate dietary iodine intake, accounts for about 10% of all cases and has greater rates of recurrence and metastasis. As radiation exposure is recognized as a risk factor for thyroid cancer, increased incidence is being observed in people who received radiation therapy directed at the neck (a common treatment in the 1950s for enlarged thymus, adenoids, and tonsils and for skin disorders) or who were exposed to iodine-125, for example, from the Chernobyl nuclear power-plant accident. However, based on 11 deaths, a statistically significant association between exposure and thyroid cancer-specific mortality was found both when analyzed in terms of log increments in the exposure opportunity scores and when comparing high- versus low-exposure groups (Yi et al. No pathology was available, and no clinical information on the patients was reported. With limited deaths, mortality risk estimates were imprecise and not statistically significant for any of the groups of workers. They are among the most common types of cancer induced by environmental and therapeutic agents. This classification was updated in 2016 and reviewed by several academics and clinicians (Arber et al. Myeloid cells include monocytes and three types of granulocytes (neutrophils, eosinophils, and basophils). All of these mature cells circulate in the blood and are collectively referred to as white blood cells or leukocytes. Monocytes move out of the bloodstream into inflamed tissues, where they differentiate into macrophages or dendritic cells. Antigen stimulation induces the T cells to differentiate into several subtypes involved in cell-mediated immunity, immune regulation, and the facilitation of B cell function. Progenitor or pre-B cells mature in the bone marrow into antigen-specific B cells. As the leukemic cells (blasts) fill the bone marrow, they actively secrete cytokines that prevent normal cellular proliferation, leading to reduced circulating normal blood cells. Lymphoma is a general term for malignancies that arise from lymphocytes (B, T, or natural killer cells). Lymphomas generally present as solid tumors at lymphoid proliferative sites, such as lymph nodes and the spleen. As stem cells mature into B or T cells, they pass through several developmental stages, each with unique functions. B cells give rise to a wide array of neoplasms, which are characterized by the stage at which B-cell development was arrested, as well as by the surface protein expression and the genetic characteristics of the malignant cells. Multiple myeloma is a lymphohematopoietic malignancy derived from antibody-secreting plasma cells, which also have a B-cell lineage, that accumulate primarily in the bone marrow but may also infiltrate extramedullary sites. Furthermore, the existing records that will serve as the basis of many current and even future studies will use earlier and evolving classifications, so a confounding of classification is likely to remain, even in new literature. The nomenclature has become more uniform in recent studies, but the possibility of ambiguity remains if earlier researchers did not use a unique code in accordance with some established system. Furthermore, treating these cells with benzo[a]pyrene suppresses B-cell differentiation. In addition to the occupational associations discussed below, higher rates of the disease have been observed in people who have suppressed or compromised immune systems. Other populations of Vietnam-era veterans likewise did not find an association (Anderson et al. A proportionate mortality ratio analysis that compared the experience of 33,833 U. Studies of Australian, New Zealander, and Korean veterans who served in Vietnam have also been reviewed. Subsequent findings have not contradicted those conclusions, especially given that most studies have had low statistical power, as was seen in the current extended follow-ups of occupational cohorts that reported two (Collins et al. The incidence rate is about 50% higher in white and black men than in women of the same race and is highest for whites. Nearly all cases occur after the age of 50 years, and the median age of diagnosis is 70 years. Additional information available to the committees responsible for later updates has not changed that conclusion. Risks were not significantly increased among the Dow Chemical Company Midland, Michigan, or Plymouth, New Zealand, chemical production workers, phenoxyherbicide sprayers, or 2,4-D production workers (Bloemen et al. A study of a subcohort of Hispanic workers in a larger cohort of 139,000 California members of the United Farm Workers of America (Mills et al. However, the extent of intercorrelation of these persistent organic pollutants greatly curtails the degree to which any effect can be specifically attributed to dioxin-like activity. Lymphoid leukemia showed a nonstatistically significant decreased risk based on nine low-exposure and five high-exposure deaths. However, providers were not blinded to exposure status, and, because patients were younger, these factors may have influenced the therapy paradigm used. Information on demographics, laboratory and disease-related parameters at the time of the initial diagnosis, and the type and number of treatments received was taken from medical records. The Cox proportional hazards model included age, Rai stage, and baseline laboratory parameters. Dust samples were collected and analyzed from vacuum cleaners for participants who had used their vacuum cleaner within the past year and owned at least half of their carpets or rugs for 5 years or more. Nor has long-term exposure to phenoxy herbicides or cacodylic acid resulted in an increased incidence of lymphomas in laboratory animals. It is known to be increased in B-cell neoplasms, including multiple myeloma and various lymphomas, and especially diffuse large B-cell lymphomas (Hussein et al. The authors found a higher prevalence of cells carrying the translocation in the farmers whose blood had been drawn during a period of high pesticide use than in those whose blood had been drawn during a low-use period. In most cases of follicular lymphoma, tumor cells carry the t(14;18) chromosomal translocation, and there is evidence that an increased frequency of lymphocytes from the peripheral blood carrying this tumor marker may be a necessary but not sufficient step toward the development of follicular lymphoma (Roulland et al. When examining immunoglobulin (IgG, IgA, IgM, IgD, and IgE) and complement (C3 and C4) concentrations measures of humoral immunity, Saberi Hosnijeh et al. Limiting the analyses to workers from Factory A and examining serum concentrations of 16 cytokines, 10 chemokines, and 6 growth factors, Saberi Hosnijeh et al. Plasma cell neoplasms are lymphoid neoplasms of terminally differentiated B cells, all of which exhibit the expansion of a single clone of Ig-secreting plasma cells. The condition is typically discovered as an incidental finding when a protein electrophoresis test is performed for reasons unrelated to plasma cell dyscrasias. The presence of one of two factors (an abnormal serum free light-chain ratio and a high serum M protein level [ 1. After an adjustment for competing causes of death, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years (Kyle et al. Data and biospecimens were collected prospectively from individuals to whom structured questionnaires and physical exams were given at set times over 20 years, with the final exam conducted in 2002. The study included 479 Ranch Hand veterans (who conducted aerial spray missions of the herbicides from 1962 to 1971) and 479 controls (comparison veterans who were also in the Air Force and had similar job duties and were deployed to Southeast Asia during the same period) who participated in the 2002 follow-up examination and had given a serum specimen and were at least 50 years old at the 2002 follow-up. The incidence of multiple myeloma is highly age-dependent and is relatively low in people under 40 years old.

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Firefighters, who are routinely exposed to numerous pyrolysis products, have a significantly increased mortality risk after 20 or more years of employment (Youakim, 2006). Results were reported separately for kidney cancer (n = 186 cases) and renal pelvis cancer (n = 23 cases), but no excess cancer risk for the kidney or renal pelvis was found when compared with the general Korean population (Yi, 2013) or when internal comparisons of high- versus low-exposure-opportunity scores were made (Yi and Ohrr, 2014). When kidney, renal pelvis, and ureter cancer deaths were combined for the internal cohort comparison of high versus low exposure, no excess cancer mortality was found (Yi et al. Information on smoking or other lifestyle habits was not available for this cohort during the follow-up through 2003, and thus the modest associations could be due to confounding by smoking or obesity. Studies of Vietnam veterans have not found statistically significant associations between deployment and presumed exposure to the herbicides and incidence or mortality of renal cancers. Similarly, no increases of risk or mortality from renal cancers have been reported among the several occupational cohorts, where exposure was often better characterized. Several types of cancer are usually grouped together; although this may bias results in unpredictable ways, the most likely consequence is a dilution of risk estimates toward the null. Other environmental exposures-such as to petroleum products, electromagnetic fields, and cell-phone use-are unproven as risk factors (Gomes et al. The causes of most cancers of the brain and other portions of the nervous system are unknown. The committees responsible for Update 1996, Update 1998, Update 2000, Update 2002, and Update 2004 did not change that conclusion. That committee considered one study that suggested a relationship between phenoxy acid herbicides and adult gliomas (W. Vietnam veterans nurses study is limited by the issue of multiple comparisons, the possibility of false positives, and imprecise risk estimates. No date or language parameters were applied, and a total of 153 articles were found. The study is limited by the lack of specific exposure information; industry and occupation information was incomplete in the registry (of the initially eligible subjects, 34% of cases and 38% of controls were excluded from the final sample due to missing information), restricted to "usual" or "longest held" job, and obtained from the medical record at the time of diagnosis and subject to misclassification. Therefore, while these data are consistent with some other studies that suggest an agricultural chemical exposure risk for brain cancer, they are very nonspecific and must be considered exploratory. Hearing from the scientific experts ensured that the committee had information that was as complete and current as possible regarding the science of glioblastoma, whereas hearing from the families of veterans who had been diagnosed with glioblastoma provided a reminder of the burden of the disease. Although a relatively small number of all new cancer cases each year originate in the brain or nervous system for both men and women (1. In the United States, incidence is about 50% higher in males than in females, highest for non-Hispanics whites, and associated with higher socioeconomic status. Of interest, about 25% of glioma risk is estimated to be genetic, and current research has identified 12 common genetic variants that explain approximately 27% of the genetic risk for glioblastoma. These novel mechanisms may fundamentally change how we think about the evolution of this (and other) cancers. Odds ratios were calculated and adjusted for age, residence, medical history, and smoking. A statistically significant increased risk of multiple myeloma was observed with exposure to Mecoprop but not with exposure to 2,4-D. It is known to be increased in B-cell neoplasms, including multiple myeloma and various lymphomas (Hussein et al. In comparing the frequency of specific variants of several metabolic genes between multiple myeloma cases and controls, Gold et al. Most of these cancers also arise from B cells, so the committee hypothesized that it would be etiologically plausible for the association with multiple myeloma to belong with the lymphomas in the sufficient category. Two well-designed studies of well-characterized cohorts were reviewed in the current update. The pattern of organ involvement depends on the nature of the protein; some amyloid proteins are more fibrillogenic than others. The Amyloidosis Foundation estimates that approximately 4,500 new cases are diagnosed each year (Amyloidosis Foundation, 2018). It usually affects people from ages 50 to 80 years and occurs more often in males than in females. Historically, bone marrow biopsies emphasized routine histochemical analysis, but modern immunocytochemistry and flow cytometry now commonly identify monoclonal populations of plasma cells with molecular techniques. The National Cancer Institute estimated that in the United States in 2018, 60,300 people would receive a new diagnosis of and 24,370 men and women would die from some form of leukemia. Additional information available to the committees responsible for Update 1996 through Update 2010 did not change that conclusion. They also reported the incidence of 21 leukemias overall, which resulted in a statistically significantly elevated standaridized incidence ratio. Results were stratified by incident non-lymphoid and lymphoid leukemias, but only the lymphoid leukemia standardized incidence ratio was statistically significant. Other Identified Studies Several other studies (occupational, environmental, and case-control designs) were identified that examined leukemia outcomes, but all lacked sufficient exposure specificity (e. In this context, information in a letter to the editor of the American Journal of Hematology from Nguyen-Khac et al. Vietnam veterans, findings have been null, and risk estimates have been less than 1. Likewise, a statistically significant increased risk of death compared with the standardized U. Most involve the number of cytopenias, dependence on transfusion, cytogenetic abnormalities, and the number of blasts in the marrow. Exposures to radiation, a number of drugs, and some industrial chemicals (such as benzene) are recognized as risk factors for this condition, but it may also arise from an autoimmune disease. They followed Ahr-null mice, showing that they have diminished survival, splenomegaly, leukocytosis, and anemia. The hematopoetic stem cells showed diminished selfrenewal capacity, with somatic changes compatible with a profile of accelerated aging and hematopoetic stem cell exhaustion. Whenever the information was available, an attempt has been made to evaluate the effects of exposure on males and females separately. The categories of association and the approach to categorizing the health outcomes are discussed in Chapter 3. To reduce repetition throughout the report, Chapter 5 characterized study populations and presents design information related to new publications that report findings or that revisit study populations considered in earlier updates. Dioxin exposure has the potential to disrupt male reproductive function by altering the expression of genes that are pertinent to spermatogenesis and by altering steroidogenesis (Wong and Cheng, 2011); it has the potential to disrupt female reproductive function by altering the expression of genes relevant to ovarian follicle growth and maturation, uterine function, placental development, and fetal morphogenesis and growth (Bruner-Tran et al. The core histones that are retained in human sperm carry epigenetic modifications to maintain open nucleosomes, which permits the transcription of genes that are important during embryo development (Casas and Vavouri, 2014). The mobilization of dioxin during pregnancy may be increased because the body is drawing on fat stores to supply nutrients to the developing fetus. Data indicate that dioxin can accumulate in placental tissue and that dioxin can transfer from the placenta to the developing fetus (Mose et al. Several of these components and some health outcomes related to male fertility, including reproductive hormones and sperm characteristics, can be studied as indicators of fertility. Both are secreted into the circulatory system in episodic bursts by the anterior pituitary gland and are necessary for normal spermatogenesis. A more detailed review of the male reproductive hormones can be found elsewhere (Strauss and Barbieri, 2013). Several agents, such as lead and dibromochloropropane, affect the neuroendocrine system and spermatogenesis (for reviews, see Schrader and Marlow, 2014; Sengupta, 2013). Additional information available to the committees responsible for subsequent updates did not change these conclusions. This study was limited by its very small sample size and by a failure to use all of the semen quality markers available. It also had a confusing sampling frame with cases and controls sampled first based on an unsuccessful conception within 12 months status, and then further divided by total motile count. The paper lacked many details on the recruitment of the men, the number of men was small, and no analysis of the impact of adjustment for other factors was presented. This report is based on a well-designed study, including a prospective follow-up and adjustment for multiple potential confounders. Moreover, its utility is limited by the fact that subjects were exposed to dioxins in a different period of their life (infancy, childhood, and adolescence) than the Vietnam veterans, and the generalizability of the results is open to question.


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Neuropathies can be purely motor, presenting as deficits in strength, but most often they present with the involvement of both motor and sensory fibers. Neuropathies are often symmetric and start with symptoms related to dysfunction of fibers that travel the greatest distance to their target organ. For that reason, the symptoms of neu ropathy often start in the digits and travel toward the torso. In this update, the chapter reviews data pertinent to persistent neurologic disorders of all types. The scientific evidence supporting the biologic plausibility of each category of disorders is also reviewed here. For citations new to this update that revisit previously studied populations, the relevant details on the experimental design can be found in Chapter 5. This section summarizes in a general way some of the information reviewed in the current update and, for completeness, includes pertinent information from prior updates. Those mechanisms are im portant for maintaining the connections between nerve cells, which are necessary for neuronal function and are involved in axon regeneration and recovery from peripheral neuropathy. As discussed in Chapter 4, extrapolating observations of cells in culture or in animal models to humans is complicated by differences in sensitivity and susceptibility among animals, strains, and species; by the lack of strong evidence of organ-specific effects occurring consistently across species; and by differences in the route, dose, duration, and timing of chemical exposures. Therefore, such results were not considered by the committee when weighing the evidence for specific conclusions. Age-specific hospitalization rates were calculated using the total number of annual hospitalizations published by the Ministry of Health and the average annual resident population. Results were presented for eight categories of mental and neurologic disorders and a ninth category for "other nervous disorders. No urinary marker of 2,4-D was associated with any deficit in any of the domains of neurobehavior that were tested. Exposure was dichotomized into high and low, with the 95th percentile for each congener serving as the cutpoint. For each class (low, high, and dioxinlike), an individual was placed in the category of high if his or her level of at least one congener in that class was elevated. Thus, it is difficult to interpret the findings of this study, although it should be noted that the crosssectional nature is not a weakness, given that the halflives of these compounds are generally a decade or longer. The physical function tests were a 10foot walking test of functional mobility, a coin-flipping test of manual dexterity, a grip strength test, and a reach down test of lower body mobility. Other Identified Studies One additional study in this area was identified by the committee, but it examined biologic markers of effect of neurotransmission pathways that do not 1 p = 0. Moreover, highly chlori nated congeners were more strongly associated with increased concentration of homovanillin acid but significantly reduced concentration of vanillylmandelic acid, after adjustment for creatinine. Neither informa tion on diet nor diagnoses of hypertension were collected, which may confound the association. Its primary clinical manifestations are bradykinesia, resting tremor, cogwheel rigidity, and gait instability. Pathology findings in other forms of Parkinsonism show different patterns of brain injury and protein aggregation. Although the gold standard of diagnosis is pathology of the protein ag gregates in the brain (Lewybodies), this standard is rarely, if ever, achieved in an epidemiologic investigation due to the low rate of autopsies or brain collection. On the other hand, the longer the disease durations, the more likely it is that the diagnosis is accurate (Adler et al. Clinical accuracy also is much higher if patients are diagnosed in specialty clinics of tertiary care facilities (by movement disorder specialists). Of note, it has been proposed that the latter factors-especially smoking-may not be protective but rather a case of reverse causation (Ritz et al. Mutations associated with an autosomal recessive inheritance pattern have also been described; however, these disease genes are found in only a handful of familial cases worldwide. Two studies reviewed in Update 2008 examined the association specifically with chlorophenoxy acid and ester herbicides and found increased odds ratios (Brighina et al. Additional studies considered by the committees responsible for Update 2010 and Update 2012 led them to affirm this conclusion. Two environmental studies were also identified-one among the residents of rural central California (Narayan et al. Research on the neurotoxicity of 2,4D has been going on for a number of years, but most of it has focused on its effects on the developing rodent nervous system. The studies have often used high doses of 2,4D that have resulted in adverse changes in the developing nervous system-both neurochemical (such as changes in D2 receptors, tyrosine hydroxylase, and dopamine betahydroxylase) and behavioral (for example, Bortolozzi et al. The association was even stronger after controlling for smoking and education in a multivariate model but quite imprecise. Self-reported information on 39 specific military exposures was also collected, some of which were conflict-specific (e. Inverse probability weighting was used to adjust for potential bias from con founding, missing covariate data, and selection arising from a case group that disproportionately included longterm survivors and a control group that may or may not have differed from U. Inverse probability weights were used to adjust for potential confounding and missing covariate data biases as well as to adjust for potential selection bias among a case group that included a dispropor tionate number of longterm survivors at enrollment. Participants completed a selfadministered written survey that collected information on demographics, occupational and residential exposures, military service, and smoking history. Spe cifically, there were 58 identified exposure risk factors, 20 occupational groups, and 20 industrial groups queried for each job. Of 2,025 eligible subjects, only half (n = 1,016) agreed to participate and completed a questionnaire to assess medical history, smoking history, and medication use. The manifestations of neuropathy can include a combination of sensory changes, weakness, and autonomic instability. Peripheral neuropathy resulting from toxic exposure usually affects nerve fibers in a symmetric pattern, beginning distally in the longest fibers (in the toes) and mov ing proximally (toward the spine). As many as 30% of neuropathies are "idiopathic," that is, no etiology is determined despite exhaustive clinical evaluation. Peripheral neuropathy also occurs commonly as a complication of diabetes; its reported prevalence in people who have chronic diabetes is up to 50%. Toxicant exposure can result in earlyonset (immediate) peripheral neuropa thy or delayedonset peripheral neuropathy, which occurs years after the external exposure has ended. For classification purposes, the committee considers a neu ropathy early onset if abnormalities appear within 1 year after external exposure ends and delayedonset if abnormalities appear more than 1 year after external exposure ends. The focus of this section is on data related to delayedonset peripheral neuropathy. In both analyses, there were strong and significant associations between serum di oxin concentrations and possible and probable neuropathy, and significant trends were found with increasing concentrations of dioxin. However, there were too few nondiabetic subjects to produce useful estimates of risk in the absence of the contribution of diabetes. However, this study was limited by the small sample size and a lack of information regarding the duration of diabetes. Neuronal cell cultures treated with 2,4-D showed decreased neurite extension associated with intracellular changes, including a decrease in microtubules, an inhibition of the polymerization of tubulin, dis organization of the Golgi apparatus, and an inhibition of ganglioside synthesis (Rosso et al. The normal activity of those target processes is important for maintaining synaptic connections between nerve cells and for supporting the mechanisms involved in axon regeneration during recovery from peripheral neuropathy. Since Update 2010, only one relevant study was identi fied and reviewed, and that study was reviewed in Update 2014. The most common forms of hearing im pairment in adults are presbycusis and tinnitus. Heritable factors may influence the susceptibility to hearing loss, but external agents can also contribute. The frequency-specific deficit was hypothesized to be secondary to a postnatal hypothyroxinemia that occurred during a sensitive period for the development of the lowfrequency regions of the cochlea, which was consistent with the finding that the pups had decreased serum T4 concentrations on postnatal day 21. Most cases of diabetes mellitus are classified as being in one of two categories: type 1 diabetes or type 2 diabetes. As with many autoimmune diseases, genetic and environmental factors both influence its pathogenesis.

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The following table provides guidelines on drugs which are considered safe or relatively safe in pregnancy, drugs which should be used with caution and only when necessary, and drugs which are contraindicated. The clinical features of malaria in pregnancy depend, to a large extent, on the immune status of the woman, which in turn is determined by her previous exposure to malaria. Clinical Features 229 Non-immune (women from endemic area): High risk of maternal perinatal mortality. Acute febrile illness; severe haemolytic anaemia; hypoglycaemia; coma/convulsions; pulmonary oedema. One of the dangers of malaria in these settings is that it is not detected or suspected. Antimalarials should form part of the case management of all women with severe anaemia who are from endemic irrespective of whether they have a 230 fever or a positive blood slide [see 18. This may however be negative in a woman from endemic areas, despite placental parasitisation. If travel is not avoidable they should take special precautions in order to prevent being bitten such as using mosquito repellents and an insecticide treated bednet. Mostly twin pregnancy but others may be encountered, triplets, etc and these may be associated with use of fertility drugs. Multiple pregnancy generally 231 carries a much higher risk (antenatal, intrapartum and postpartum) than a singleton. Foetal heart rates at two different areas with a difference of 15 beats per minute. Otherwise do a Caesarean section to expedite delivery at shortest possible interval which should be the overall goal. Hypertension being defined as a blood pressure of 140/90 or higher on more than 2 occasions of about 6 hours apart. It carries a high foetal mortality and maternal morbidity and mortality if undiagnosed or poorly managed. This to titrate against level of consciousness to keep them well sedated but arousable. Other ways of isoimmunization include transfusion with Rhesus incompatible blood, ectopic pregnancy, hydatidiform mole, and abortion. Clinical Features Usually none but severe isoimmunization can lead to: Spontaneous abortion. Severely affected neonates who require exchange transfusion to avoid hyperbilirubinaemia. If he is Rh -ve then the foetus should be Rh -ve and hence no risk of isoimmunization in the mother. It is more common in pregnancy due to physiological changes that cause dilatation of the urinary system and relative stasis of urine. Recurrence cases are high and may indicate resistant organism, urologic abnormalities (e. Management - General Proper management of labour reduces maternal and perinatal mortality and morbidity. It is a graphic display of labour record to show progress of labour: cervical dilatation, descent of the head, foetal condition, maternal condition. An "alert line" and an "action line" should be noted, Parameters are charted against time. The partogram is especially useful where there is shortage of staff, and where majority of labours and deliveries are managed by midwives, clinical officers, medical officers or patients have to be transferred to other facilities for operative deliveries (e. Descent assessed by abdominal palpation, noting the number of fifths of the head felt above the pelvic brim. Management - Supportive Proper management of the first stage ensures the woman reaches second stage strong enough for safe delivery. When this happens: - placenta delivered by controlled cord traction - uterus gently massaged - placenta and membranes examined for completeness, infarcts, retroplacental clot and any other abnormalities - placenta weighed. Patient then observed closely for 1-2 hours before being transferred to the postnatal ward. Other causes of obstructed labour are malpresentations or malpositions of the foetus, and soft tissue abnormalities of the genital tract. Obstructed labour is the commonest cause of ruptured uterus and a major cause of maternal mortality. Obstructed labour and ruptured uterus can be prevented by appropriately timed Caesarean section. Clinical Features Clinical features may be insidious ("quiet") or obvious ("classical"). Alternate stitches are removed on the sixth day and all stitches on the seventh day. This is a time when complex adaptations of physiology and behaviour occur in women. Although usually a low risk period, life threatening emergencies or serious complications may occur that must be recognised and managed efficiently. Those caring for women postpartum should be sensitive to the initiation of family bonding, a special process not to be disturbed unless maternal or neonatal complications arise. Some of the maternal complications include postpartum haemorrhage, puerperal sepsis, deep vein thrombosis, psychosis, breast engorgement, mastitis or breast abscess. Retained placental fragments or membranes A common complication in which there is delay in completion of the third stage of labour. Spontaneous detachment of placenta occurs within 15 minutes - 90% of cases and 30 minutes - 95% of cases.

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Indirect adjustment was used, as age-calendar-year-specific rates from a standard population (Connecticut) were applied to the age-calendar-year distribution (of women-years) in the study population. Here is a detailed explanation: For the indirect standardization or adjustment procedure, "standard rates" were obtained from the Connecticut population. These rates were both age-specific and calendar-year specific, to control for changes in incidence over time. Thus, a table of standard rates like the following would have been used: Breast cancer incidence (per 100,000 Connecticut women per year) (hypothetical data) Age 30-34 35-39 40-44 45-49 1935-39 20 30 50 70 1940-44 22 33 54 72 Period 1945-49 1950-54 26 28 35 38 57 59 75 78 1955-59 30 40 62 81 etc. Source: Connecticut Cancer Registry (1950-1969) The weight could be population or population-time (person-years, or in this case, women-years). Boice and Monson tell us that they computed women-years within 5-year age groups and 5-year calendar time intervals (quinquennia) (which is why the above table is constructed as it is). Boice and Monson also divided the follow-up period for each woman into 5- (their lucky number!? Dividing up the follow-up period is not part of the adjustment procedure, but enables the investigators to analyze the results for different lengths of follow-up after exposure. It is not possible to calculate by the method used by Boice and Monson, since their method requires age-calendar-year specific incidence rates whereas the rates given in the question are not specific for calendar year. The advantage of this more complex adjustment procedure is that it controls for secular changes in breast cancer incidence. The 5 in the denominator is needed to obtain the annual incidence, since the numerator contains cases accumulated during 5 years. There is also a slight increased incidence in whites in Wilson County: 16 white cases observed vs. Therefore the ratio of directlystandardized rates equals the ratio of crude rates. This question asks about the situation in which there is a constant rate ratio between groups A and B within each age stratum. The assumption of a constant multiple may not hold in reality, but it may be reasonably correct with study group we are examining. Intuitively, if two populations are alike in terms of a particular variable, then that variable cannot be responsible for observed differences between them. Directly standardized rates are comparable, regardless of age distributions, because the specific rates in each population are weighted by the same external standard. So a comparison of indirectly standardized rates in this case is the same as a comparison of their crude rates, which was shown above to be valid. Relating risk factors to health outcomes Quantifying relationships between two factors or one factor and the occurrence, presence, severity, or course of disease the "Big Picture" At this point in the course, it will be good to take stock of where we are and where we are going. After a brief overview of population and health, we have thoughtfully considered the phenomenon of disease in relation to how epidemiologists study disease. Under that topic we examined issues of definition, classification, and natural history. We then turned to the question of how to measure disease frequency and extent in populations. We examined some general issues in numeracy and descriptive statistics, and then took up the fundamental epidemiologic measures of prevalence and incidence, with the latter approached as a proportion or as a rate. From there we took up the topic of standardization, which facilitates comparisons between prevalence and incidence across populations with different demographic composition, and we saw how these various measures and concepts are used in descriptive epidemiology and surveillance. For the next section of the course we will be concerned with how to investigate associations between health outcomes and potential risk factors. That task involves questions of study design, measures of association, validity, inference and interpretation. The topics of study design and measures of association are so intertwined that whichever one we begin with, it always seems that we should have begun with the other! Analytic studies provide the data for estimating measures of association and impact, but measures of association and impact motivate the design of the studies. However, the basic epidemiologic approach to relating risk factors to health outcomes is more general than the specifics of either topic. Consider a population in which a disease or some other condition occurs throughout the population but more often in persons with characteristic A. We are likely to be interested in how the existence (prevalence) or occurrence (incidence) of the disease among people with characteristic A compares with that for the population as a whole and for people with some other characteristic B (which could simply be the absence of A). Quantify the potential impact of the characteristic on the condition, if we are willing to posit a causal relationship. Now we turn to measures of However, much of epidemiology is concerned with relationships among factors, particularly with the effect of an "exposure" on "a disease". Therefore the present topic addresses the question "How strong is the relationship between two factors? Nevertheless, two factors that are strongly associated are more likely to be causally related. There are a number of ways in which the strength of the relationship between two variables can be assessed. We can, for example, assess the extent to which a change in one variable is accompanied by a change in the other variable or, equivalently, the extent to which the distribution of one variable differs according to the value of the other variable. A second perspective is the extent to which the level of one of the factors might account for the value of the second factor, as in the question of how much of a disease is attributable to a factor that influences its occurrence. Most of the measures we will cover in this topic apply to relationships between a factor that is dichotomous (binary, having two possible values) and a measure of frequency or extent, in particular, a rate, risk, or odds. Measures of association A measure of association provides an index of how strongly two factors under study vary in concert. The more tightly they are so linked, the more evidence that they are causally related to each other (though not necessarily that one causes the other, since they might both be caused by a third factor). Association - two factors are associated when the distribution of one is different for some value of the other. To say that two factors are associated means, essentially, that knowing the value of one variable implies a different distribution of the other. Consider the following two (hypothetical) tables: * Although this term and "measure of effect" have frequently been used interchangeably (e. In the absence of knowing the proportion of cases, our best estimate would be the overall proportion in the population, 0. But is we knew the proportion of cases in the sample, we could move our estimate up (if more than one-third were cases) or down (if fewer than one-third were cases). Correlation and Agreement Association is a general term that encompasses many types of relationships. Two important ones are: Correlation is a type of association in which the relationship is monotonic, i. Linear correlation (measured by the Pearson product-moment correlation coefficient) assesses the extent to which the relationship can be summarized by a straight line. Nonparametric correlation coefficients, such as the Spearman rank correlation coefficient, assess the extent to which the two factors are correlated For example, two sphygmomanometers should give the same readings when used on the same person on the same occasion, not merely readings that are correlated. Two measurements of a stable phenomenon should agree with each other, not merely correlate. If one of the measures is known to be highly accurate and the other is being assessed, then we can assess validity of the latter, rather than merely agreement between the two.

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Hematogenous spread Typical for all sarcomas and certain carcinomas- the spread appears to be selective with seed and soil phenomenon. Lung & liver are common sites of metastasis because they receive the systemic and venous out flow respectively. In the circulation, tumour cells form emboli by aggregation and by adhering to circulating leukocytes particularly platelets. Cancer Epidemiology the only certain way to avoid cancer is not to be born, to live is to incur the risk. Over the years cancer incidence increased in males while it slightly decreased in females (due to largely screening Procedures-cervical, breast etc. In the studied populations the most common cancer in males is broncogenic carcinoma while breast carcinoma in females. Acute leukemias and neoplasms of the central nervous system accounts for about 60% of the deaths. Geographic factors (geographic pathology): Specific differences in incidence rates of cancers are seen worldwide. Inherited cancer syndromes (Autosomal dominant) with strong familial history include Familial retinoblastomas usually bilateral, and a second cancer risk particularly osteogenic sarcoma. Oncosupressor gene is the basis for this carcinogenesis 196 - Familial adenomatous polyps of the colon. Endometrial hyperplasia Cervical dysplasia Bronchial dysplasia Regenerative nodules - endometrial carcinoma - cervical cancer - bronchogenic carcinoma - liver cancer Certain non-neoplastic disorders may predispose to cancers. Chronic atrophic gastritis Solar keratosis of skin Chronic ulcerative colitis Leukoplakia of the oral cavity, vulva and penis - squamous cell carcinoma - gastric cancer - skin cancer - colonic cancer Certain types of benign neoplasms Large cumulative experiences indicate that most benign neoplasms do not become malignant. Molecular Basis of Cancer (Carcinogenesis) Basic principles of carcinogenesis: the fundamental principles in carcinogenesis include 1) Non-lethal genetic damage lies at the heart of carcinogenesis. Such genetic damage (mutation) may be acquired by the action of environmental agents such as chemicals, radiation or viruses or it may be inherited in the germ line. However, initiation alone is not sufficient for tumour formation and thus, promoters can induce tumours in initiated cells, but they are non-tumourogenic by themselves. Furthermore, tumours do not result when a promoting agent applied before, the initiating agent. Promoters render cells susceptible to additional mutations by causing cellular proliferation. Directly acting compound these are ultimate carcinogens and have one property in common: They are highly reactive electrophiles (have electron deficient atoms) that can react with nucleophilic (electron-rich) sites in the cell. Indirect acting compounds (or pro-carcinogens) Requires metabolic conversion in vivo to produce ultimate carcinogens capable of transforming cells. Most known carcinogens are metabolized by cytochrome p-450 dependent monooxygenase. Examples of this group include polycyclic and heterocyclic aromatic hydocarbones, and aromatic amines etc. These chemical carcinogens lead to mutations in cells by affecting the functions of oncogenes, onco-suppressor genes and genes that regulate apoptosis. Miners for radioactive elements-lung cancer Therapeutic irradiations have been documented to be carcinogenic. Thyroid cancer may result from childhood & infancy irradiation (9%), and by the same taken radiation therapy for spondylitis may lead to a possible acute leukemia year later. In atomic bonds dropped in Hiroshima and Nagasaki initially principal cancers were acute and chronic mylogenous leukemias after a latent of about 7 years solid tumours such as breast, colon, thyroid and lung cancers) increased in incidence. In intermediate category are cancers of the breast, lungs, and salivary glands In contrast, skin, bone and gastrointestinal tract are relatively resistant to radiationinduced neoplasia. The infection of B- cell is latent and the latently infected B-cell is immortalized. The actively dividing B- cells are at increased risk of mutations (t- 8; 14) translocation that juxta - pose C- myc with one of Immuno- globuline gene loci. Helicobacter pylori There is an association between gastric infections with helicobacter pylori as a cause of gastric lymphoma. The lymphoid cells reside in the marginal zones of lymphoid follicles and hence alternatively named as mantle zone lymphoma. Although cancer evaluation may suggest one or the other, the only unequivocal benign mass is the excised and histopathologically diagnosed one. Effects of tumour on the host: Both benigin and malignant neoplasms may cause problems because of 1. Neoplasms in the gut (both bening and malignant may cause obstruction as they enlarge Benign neoplasms more commonly of endocrine origin may produce manifestations by elaboration of hormones. For example a benign B- cell adenoma of pancreatic islets less than 1 cm in diameter may produce sufficient insulin to cause fatal hypoglycemia the erosive destructive growth of cancers or expansile pressure on benign tumour of any natural surface may cause ulceration secondary infection and bleeding. Cancer cachexia Cachexia is a progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia and anemia. The origin of cancer cachexia are obscure Clinically anorexia is a common problem in patients with cancer. Reduced food intake has been related to abnormalities in taste and central control of appetite. In patents with cancer, calorie expenditure often remains high and basal metabolic rate is increased despite reduced food intake. Paraneoplastic syndromes Paraneoplastic syndrome is an aggregate of symptom complexes in cancer - bearing patients that can not readily be explained either by the local or distant spread of the tumour or by the elaboration of hormones indigenous to the tissue from which the tumour arose Paraneoplastic syndrome occurs in about 10% of patients with malignant disease Despite its infrequency, the syndrome is important for three reasons: 1. In affected patients, they may represent significant clinical problems and may even be lethal. Laboratory Diagnosis of Cancer Every year approach to laboratory diagnosis of cancer becomes more complex more sophisticated and more specialized with time. Clinical data are invaluable for optimal pathologic diagnosis for example radiation changes in the skin or mucosa can be similar to cancer and similarly section taken from a healing fracure can mimic remarkably an osteosarcoma. The laboratory sample to be diagnosed need to be adequate, representative and well preserved Several sampling approaches are available: 1. Advanced techniques Immunocytochemistry Flow cytometry Tumour markers Excisional biopsy Selection of an appropriate site for biopsy of a large mass requires awareness that the margins may not be representative and the center largely necrotic. Appropriate preservation of specimens is obvious thus, formalin for routine fixation glutaraldehide for electron microscopy prompt refrigration to permit optimal hormone by receptor analysis 207 Requesting, "quick frozen section" diagnosis is sometimes desirable for determining (for example in breast carcinoma) for evaluating the margins of an excised cancer to ascertain that the entire neoplasm has been removed. Fine needle aspiration the procedure involves aspirating cell and attendant fluid with a small needle followed by cytologic examination of the stained smear this method is used most commonly for the assessment of readily palpable lesions such as breasts, thyroid and lymph nodes etc. It is also used for the identification of tumour cell in abdominal, pleural joint and cerebrospinal fluids Tumour markers Tumour markers are biochemical indicators of the presence of a tumour. Tumour markers can not be construed as primary modalites for the diagnosis of cancer and thus, act as supportive laboratory tests. Immunocytochemistry the availability of specific monoclonal antibodies has greatly facilitates the identification of cell products and surface markers. Some examples of utility of immunocyto chemistry in the diagnosis of malignant neoplasms are 209 o Categorization of undifferentiated malignant tumours here intermediate filaments are important. Learning objectives By the time the student is through with this lecture note he/she should be able to: 1. Introduction Human beings are subjected to a variety of metabolic diseases, as we are a complex set of structures that function through quite a varied and intertwined metabolic processes. Most metabolic diseases have genetic basis while some are acquired in life or need the complex interplay between nature and nurture for their existence. Genetic diseases either follow a single gene disorder or a polygenic basis with multifactorial disorders. Metabolic diseases with a single gene disorder these metabolic diseases follow a Mendelian type of inheritance i. Phenylketonuria, Galactosemia, Glycogen storage diseases); and x-linked recessive disorders (e. These are all rare Biochemical genetic diseases and they are beyond the scope of this lecture note. Metabolic disease with a polygenic disorder these metabolic diseases have multifactorial modes of inheritance.

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Bolus Insulin Many individuals with type 2 diabetes may require mealtime bolus insulin dosing in addition to basal insulin. Premixed Insulin pulmonary disease and is not recommended in patients who smoke or who recently stopped smoking. U-500 regular insulin, by definition, is five times as concentrated as U-100 regular insulin and has a delayed onset and longer duration of action than U-100 regular, possessing both prandial and basal properties. These concentrated preparations may be more comfortable for the patient and may improve adherence for patients with insulin resistance who require large doses of insulin. Inhaled Insulin Inhaled insulin is available for prandial use with a more limited dosing range. In general, three times daily premixed analog insulins have been found to be noninferior to basal-bolus regimens with similar rates of hypoglycemia (62). Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, doubleblind, placebo-controlled trial. Diabetes medications as monotherapy or metforminbased combination therapy for type 2 diabetes: a systematic review and meta-analysis. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. For prevention and management of diabetes complications in children and adolescents, please refer to Section 12 "Children and Adolescents. Modifiable abnormal risk factors should be treated as described in these guidelines. Cardiovascular disease and risk management: Standards of Medical Care in Diabetesd2018. Hypertension, defined as a sustained blood pressure $140/90 mmHg, is common among patients with either type 1 or type 2 diabetes. Screening and Diagnosis Recommendations c c c Blood pressure should be measured at every routine clinical visit. B All hypertensive patients with diabetes should monitor their blood pressure at home. E Blood pressure should be measured by a trained individual and should follow the guidelines established for the general population: measurement in the seated position, with feet on the floor and arm supported at heart level, after 5 min of rest. Orthostatic blood pressure measurements should be checked on initial visit and as indicated. Moreover, home blood pressures may improve patient medication adherence and thus help reduce cardiovascular risk (8). Therefore, patients with type 1 or type 2 diabetes who have hypertension should, at a minimum, be treated to blood pressure targets of,140/90 mmHg. Intensification of antihypertensive therapy to target blood pressures lower than,140/90 mmHg (e. Such intensive blood pressure control has been evaluated in large randomized clinical trials and meta-analyses of clinical trials. Taken together, these meta-analyses consistently show that treating patients with baseline blood pressure $140 mmHg to targets,140 mmHg is beneficial, while more intensive targets may offer additional, though probably less robust, benefits. Individualization of Treatment Targets Patients and clinicians should engage in a shared decision-making process to determine individual blood pressure targets, S88 Cardiovascular Disease and Risk Management Diabetes Care Volume 41, Supplement 1, January 2018 Table 9. Similar to the factors that influence management of hyperglycemia, factors that influence blood pressure treatment targets may include risks of treatment (e. Patients who have higher risk of cardiovascular events (particularly stroke) or albuminuria and who are able to attain intensive blood pressure control relatively easily and without substantial adverse effects may be best suited for intensive blood pressure targets. A Patients with confirmed office-based blood pressure $160/100 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of two drugs or a single-pill combination of drugs demonstrated to reduce cardiovascular events in patients with diabetes. B Initial treatment for people with diabetes depends on the severity of hypertension (Fig. Single-pill antihypertensive combinations may improve medication adherence in some patients (25). A meta- analysis of randomized clinical trials found a small benefit of evening versus morning dosing of antihypertensive medications with regard to blood pressure control but had no data on clinical effects (35). In two subgroup analyses of a single subsequent randomized controlled trial, moving at least one antihypertensive medication to bedtime significantly reduced cardiovascular events, but results were based on a small number of events (36). B Resistant hypertension is defined as blood pressure $140/90 mmHg despite a therapeutic strategy that includes appropriate lifestyle management plus a diuretic and two other antihypertensive drugs belonging to different classes at adequate doses. Prior to diagnosing resistant hypertension, a number of other conditions should be excluded, including medication nonadherence, white coat hypertension, and secondary hypertension. Mineralocorticoid receptor antagonists also reduce albuminuria and have S90 Cardiovascular Disease and Risk Management Diabetes Care Volume 41, Supplement 1, January 2018 Figure 9. A 2014 Cochrane systematic review of antihypertensive therapy for mild to moderate chronic hypertension that included 49 trials and over 4,700 women did not find any conclusive evidence for or against blood pressure treatment to reduce the risk of preeclampsia for the mother or effects on perinatal outcomes such as preterm birth, smallfor-gestational-age infants, or fetal death (47). Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralzine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (46). Diuretics are not recommended for blood pressure control in pregnancy but may be used during late-stage pregnancy if needed for volume control (46,48). There is evidence for benefit from even extremely low, less than daily statin doses (51). Statin Treatment Recommendations c c c In adults not taking statins or other lipid-lowering therapy, it is reasonable to obtain a lipid profile at the time of diabetes diagnosis, at an initial medical evaluation, and every 5 years thereafter if under the age of 40 years, or more frequently if indicated. In clinical practice, providers may need to adjust the intensity of statin therapy based on individual patient response to medication (e. Meta-analyses, including data from over 18,000 patients with diabetes from 14 randomized trials of statin therapy (mean follow-up 4. For patients who do not tolerate the intended intensity of statin, the maximally tolerated statin dose should be used. The relative benefit of lipid-lowering therapy has been uniform across most subgroups tested (53,61), including subgroups that varied with respect to age and other risk factors. Recently, risk scores and other cardiovascular biomarkers have been developed for risk stratification of secondary prevention patients (i. However, heterogeneity by age has not been seen in the relative benefit of lipid-lowering therapy in trials that included older participants (53,60,61), and because older age confers higher risk, the absolute benefits are actually greater (53,65). In the Heart Protection Study (lower age limit 40 years), the subgroup of ;600 patients with type 1 diabetes had a proportionately similar, although not statistically significant, reduction in risk as patients with type 2 diabetes (55). Together, they found reductions in nonfatal cardiovascular events with more intensive therapy, in patients with and without diabetes (53,57,64). These three large trials comprised over 75,000 patients and 250,000 patient-years of follow-up, and approximately one-third of participants had diabetes. Patients were randomized to receive subcutaneous injections of evolocumab (either 140 mg every 2 weeks or 420 mg every month based on patient preference) versus placebo. Importantly, similar benefits were seen in prespecified subgroup of patients with diabetes, comprising 11,031 patients (40% of the trial) (73).

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The lung and liver are not significant contributors in the metabolism of remifentanil. Terminal elimination half-life is 10 to 20 minutes, however, the effective 727 Micormedex NeoFax Essentials 2014 biological half-life is 3 to 10 minutes. Clearance rates were 90 mL/kg/min in 5 days to 8 weeks of age infants, 92 mL/kg/min in children older than 2 months to younger than 2 years, 76 mL/kg/min in children 2 to 6 years of age, and 46 to 59. Monitoring Vital signs, especially oxygen saturation, should be continuously monitored for evidence of apnea or respiratory depression during administration and following the discontinuation of infusion. Monitor for skeletal muscle rigidity, including chest wall rigidity and an inability to adequately ventilate [3]. Special Considerations/Preparation Ultiva(R): Available in 3-mL, 5-mL, and 10-mL vials containing 1 mg, 2 mg, and 5 mg, respectively, of remifentanil lyophilized powder for solution. The reconstituted solution should then be diluted to a final concentration of 20, 25, 50, or 250 mcg/mL prior to administration. Stable for 24 hours at room temperature after reconstitution and further dilution. A final concentration of 20 or 25 mcg/mL for pediatric patients 1 year or older is recommended [3]. Terminal Injection Site Compatibility 728 Micormedex NeoFax Essentials 2014 Remifentanil 0. Terminal Injection Site Incompatibility Amphotericin B cholesteryl, amphotericin B lipid complex, daptomycin, pantoprazole. Stoppa F, Perrotta D, Tomasello C et al: Low dose remifentanyl infusion for analgesia and sedation in ventilated newborns. Prophylaxis for high-risk contacts of invasive H influenzae type b disease: 10 mg/kg per dose orally every 24 hours, for 4 days. Uses Used in combination with vancomycin or aminoglycosides for treatment of persistent staphylococcal infections [1] [2] [3]. Pharmacology Rifampin is a semisynthetic antibiotic with a wide spectrum of antibacterial activity against staphylococci, most streptococci, H influenzae, Neisseria species, Legionella, Listeria, some Bacteroidesspecies, Mycobacterium tuberculosis, and certain atypical mycobacterium. Rapidly deacetylated to desacetylrifampin (active metabolite) and undergoes enterohepatic circulation. Rifampin in a potent inducer 731 Micormedex NeoFax Essentials 2014 of several cytochrome P450 enzymes. If administered concomitantly, the following drugs may have decreased pharmacologic effects due to increased metabolism: aminophylline, amiodarone, cimetidine, corticosteroids, digoxin, enalapril, fluconazole, midazolam, morphine, phenobarbital, phenytoin, propranolol, and zidovudine. Special Considerations/Preparation Available as a lyophilized powder for injection in 600-mg vials. Reconstitute with 10 mL of sterile water for injection to make a final concentration of 60 mg/mL. Shama A: Intravenous rifampicin in neonates with persistent staphylococcal bacteraemia. Prophylaxis for high-risk contacts of invasive meningococcal disease: 5 mg/kg per dose orally every 12 hours, for 2 days. Adverse Effects Causes orange/red discoloration of body secretions (eg, sweat, urine, tears, sputum). Preparation of oral suspension using capsules yields variable dosage bioavailability. Uses Skeletal muscle relaxation/paralysis in infants requiring endotracheal intubation. Pharmacology Rocuronium is an amino steroid nondepolarizing neuromuscular blocking agent that is an analog of vecuronium with 10% to 15% of its potency. Onset of clinical effect usually occurs within 2 minutes and the duration ranges from 20 minutes to 2 hours. It can have differential effects on various muscle groups (eg, laryngeal vs adductor pollicis vs diaphragm). Despite this difference, rocuronium has the fastest onset of any currently available nondepolarizing muscle relaxant. Adverse Effects the use of rocuronium in infants has only been studied in patients under halothane anesthesia. Respiratory and metabolic acidosis prolong the recovery time, respiratory alkalosis shortens it. Rocuronium may be associated with increased pulmonary vascular 735 Micormedex NeoFax Essentials 2014 resistance, so caution is appropriate in patients with pulmonary hypertension. Monitoring Assess vital signs frequently and blood pressure continuously if possible. Special Considerations/Preparation Zemuron for intravenous injection is available in 5 mL and 10 mL multiple-dose vials containing 10 mg/mL. Upon removal from refrigeration to room temperature storage conditions (25 degrees C/77 degrees F), use within 60 days. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine and edrophonium. Plasma levels of rocuronium follow a three compartment open model following intravenous administration. The rapid distribution half-life is 1 to 2 minutes and the slower distribution half-life is 14 to 18 minutes. The onset of laryngeal adductor paralysis is significantly slower with rocuronium compared with succinylcholine. Rocuronium is approximately 30% protein bound, and is primarily excreted by the liver. Most pediatric patients anesthetized with halothane who did not receive atropine for induction experienced a transient increase (30% or greater) in heart rate after intubation, whereas only 1 of 19 infants anesthetized with halothane and fentanyl who received atropine for induction experienced this magnitude of change. Aminoglycosides, vancomycin, and hypermagnesemia may enhance neuromuscular blockade. Rocuronium may be associated with increased pulmonary vascular resistance, so caution is appropriate in patients with pulmonary hypertension. The package insert statement that rocuronium is not recommended for rapid sequence intubations in pediatric patients is due to the lack of studies. Special Considerations/Preparation 737 Micormedex NeoFax Essentials 2014 Zemuron for intravenous injection is available in 5 mL and 10 mL multiple-dose vials containing 10 mg/mL. The solution is clear, colorless to yellow/orange, and is adjusted to isotonicity with sodium chloride and to a pH of 4 with acetic acid and/or sodium hydroxide. Eikermann M, Hunkemoller I, Peine L, et al: Optimal rocuronium dose for intubation during inhalation induction with sevoflurane in children. The recommended vaccination schedule is 2 months of age (minimum age 6 weeks and maximum age 14 weeks 6 days), 4 months of age, and 6 months of age (maximum age 8 months). Pharmacology RotaTeq is a bovine-based pentavalent vaccine containing 5 live reassortant rotaviruses. The fifth reassortant virus expresses the attachment protein (P1A[8]) from the human rotavirus parent strain and the outer capsid protein G6 from the bovine rotavirus parent strain. Each vaccine dose contains sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell-culture media, and trace amounts of fetal bovine serum. Analysis of these events revealed a persistent clustering of events during days 3 to 6 after administration of the first dose. Transmission of vaccine virus strains from vaccinees to non-vaccinated contacts has been reported. In clinical studies, vaccine virus shedding was noted from 1 day to 15 days after a dose. Special Considerations/Preparation RotaTeq is supplied as a suspension for oral use in individually pouched single-dose tubes. Vaccination should not be initiated for infants 15 weeks, 0 days of age and older [2] [3]. Vaccination should be deferred in infants with acute moderate to severe gastroenteritis, and infants with moderate to severe acute illness [3]. The rotavirus parent strains of the reassortants were isolated from human and bovine hosts.

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Infections may spread through the tissues causing cellulitis and present with fever, swollen face, pain and malaise. Comments: Dental consult is needed because deep periodontal scaling or extraction of the tooth is necessary to eliminate the infected pulp. Acute necrotizing ulcerative gingivitis Signs and symptoms includes foul breath, gingival pain, malaise, thick ropy saliva, with or without fever. On examination of the oral cavity, the gingiva is edematous and ulcerated with a pseudomembrane on the interdental papillae. Antibiotic therapy should be followed within a few days by localized gingival curettage by a dentist and oral rinses with 0. Juvenile periodontitis this condition occurs in otherwise healthy children and is localized to the molar and incisor regions. Deep gingival pocketing and bone resorption occur and may cause tooth loss in this area. Dental consult is necessary; it can usually be controlled with root debridement and plaque control only. If condition does not respond to conservative management then antibiotics should be started. Periodontal abscess this condition manifests as a red, fluctuant swelling of the gingiva, which is extremely tender to palpation. After abscess resolution, infected pulpal tissues should be removed by subgingival scaling and root planing. Antibiotic treatment is only necessary if any of the following are present: acute onset facial or oral swelling, swelling inferior to the mandible, trismus, dysphagia, lymphadenopathy, fever >38. Pericoronitis Microorganisms and debris may be impacted under the soft tissue overlying the crown of the tooth in a third molar or any erupting permanent teeth. If the natural drainage is blocked, this may lead to infection of adjacent soft tissues and fascial spaces. The infection is lifethreatening due to the possibility of asphyxia and aspiration pneumonia. Typically, there is no lymphadenopathy, but with tender, symmetric, "woody"induration. Comments: Mainstays of treatment include management of the airway, empiric antibiotics. Antibiotic treatment is only necessary for systemic signs such as fever and lymphadenopathy. For cases of acute diarrhea with dysentery (blood in the stool), give ciprofloxacin for 3 days. For suspected antibioticassociated colitis, mild disease does not warrant antibiotic treatment since symptoms resolve within 7-10 days after discontinuing precipitating antibiotics. Immunization of infants starting at 6 weeks of age with either of 2 available live attenuated rotavirus vaccines is recommended to afford protection against severe rotavirus disease. The monovalent human rotavirus vaccine is given as a 2-dose series and the pentavalent human bovine rotavirus vaccine is given as a 3-dose series. Treat at 5 days and perhaps longer if documented bacteremia Comments: Perform analysis (check bleeding parameters first), Gram stain and culture of peritoneal fluid to distinguish primary from secondary peritonitis. Secondary peritonitis Etiology: Usually polymicrobial consisting of anaerobes and facultative gramnegative bacilli: Bacteroides fragilis group, Peptostreptococcus, E. Comments: Patient may require either immediate surgery to control the source of contamination and to remove necrotic tissue, blood and intestinal contents from the peritoneal cavity or a drainage procedure if a limited number of large abscesses can be shown. Infection almost always limited to abdominal cavity; complicating bacteremia is rare. Comments: P: Hepatitis A vaccine is given intramuscularly as a 2-dose series at a minimum age of 12 months. Immunoglobulin might be preferred over Hepatitis A vaccination among seronegative individuals with significant underlying liver disease (Sanford Guide to Antimicrobial Therapy, 2016). When symptomatic, common complaints include fatigue, nausea, anorexia, myalgias, arthralgias, asthenia, weight loss (except where ascites). If symptomatic, usually abates in days to weeks; rarely associated with hepatic failure. For anaerobic or mixed infections piperacillin-tazobactam, ertapenem (or other carbapenem) are sufficiently active alone and metronidazole may be discontinued. Gallbladder infection Etiology: Acute acalculous cholecystitis is uncommon in children and usually caused by an infection secondary to Groups A and B Streptococci, Gram-negative bacilli (like Salmonella) and Leptospirosis interrogans. Comments: Laparoscopic cholecystectomy is the most common surgical treatment for acute calculous or acalculous cholecystitis in over 95% of pediatric cases. Other treatment options when laparoscopic or open cholecystectomy is not feasible include cholecystostomy. Biliary complicated intra-abdominal infections Clinical Setting: Community-acquired acute cholecystitis of mild-tomoderate severity Community-acquired acute cholecystitis of severe physiologic disturbance, advanced age, or immunocompromised state Acute cholangitis following bilio-enteric anastamosis of any severity. Normalization of serum procalcitonin concentration may assist in customizing the duration of therapy. Some centers continue antibiotics until the serum procalcitonin serum concentration is <0. Those with necrosis involving 30% or more of the pancreas are at greatest risk of developing infection. Nelson Textbook of Pediatrics, 20th edition, Philadelphia, Pennsylvania: Elsevier Inc, 2016. Antibiotic management of complicated intra-abdominal infections in adults: the Asian perspective, Annals of Medicine and Surgery 3 (2014) 85-91 Lucero M, Saniel M, Geronimo J, Ang C, Leano F, Mate R, Trajano E, Sanvictores E, Forbes Z, Tupasi T. Retrospective analysis of azithromycin versus fluoroquinolones for the treatment of legionella pneumonia. Philippine Foundation for Vaccination and the Philippine Society for Microbiology and Infectious Diseases. Saniel M, Moriles R, Monzon O, Salazar N, Leano F, Trajano B, Sombrero L, Mat R, Villanueva J, Geronimo J, Balis A. The relative importance of various enteropathogen in the etiology of acute diarrhea: a hospital-based study in urban Philippines. Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Consensus guidelines for the prevention and treatment of catheterrelated infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Treatment involves patient education about disease chronicity and need for long term commitment to lid hygiene with regular application of warm compresses, gentle lid massage and lid washing. Topical antibiotic steroid combination during the acute phase for around 2 to 4 weeks. The decision to use an antibiotic-steroid combination will depend on the judgment call of the physician on the degree of inflammation involved. It is best to obtain specimen for culture and sensitivity testing prior to treatment initiation. Orbital cellulitis is a serious infection with risk of cavernous sinus thrombosis. Surgical debridement is warranted with abscesses or if medical management fails to lead to an improvement in the first 24-36 hours. Hospitalization may be considered in cases of suppurative bacterial infection with associated lacrimal gland abscess. Canaliculitis (Lacrimal apparatus) Etiology: Actinomyces, Staphylococci, Streptococci; fusobacterium, Nocardia sp. Referral to ophthalmologist for removal of granules and local irrigation with an antibiotic solution. Topical Gentamicin, Ciprofloxacin 6-8x/d Comments: Hyperpurulent discharge is observed.

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If the person vomits and is on dry land, roll them into a side-lying recovery position to prevent aspiration (or choking). If possible, use a protective barrier, such as disposable latex-free gloves, gauze or even Responding to Emergencies 359 Water-Related Emergencies a handkerchief. If the person is still in the water, gently roll the person partially while maintaining stabilization and clear the vomit. Moving an Unresponsive Person to Dry Land If you are on a sloping shore or beach, you can use a beach drag to remove an unresponsive person from the water for the purpose of giving care. Always call 9-1-1 or the designated emergency number when a person has been involved in a drowning incident, even if the person is responsive and you think the danger has passed. Complications can develop as long as 72 hours after the incident and may be fatal. Helping Someone Who Has Fallen Through Ice If a person falls through the ice, do not go onto the ice to attempt a rescue, as the ice may be too thin to support you. It is your responsibility as a trained lay responder to call 9-1-1 or the designated emergency number immediately. In the case of a drowning person, always attempt to rescue the person using reaching and throwing assists (Figure 20-5) if you can safely do so. If you are able to safely pull the person from the water, give care for hypothermia as you learned in Chapter 19. Use reaching and throwing assists to rescue a drowning person who has fallen through the ice. The American Red Cross has swimming courses for people of any age and swimming ability. Never leave children unattended or unsupervised around water, including bathtubs, toilets, wading pools or buckets of water. Children or inexperienced swimmers should take extra precautions, such as wearing a U. Be knowledgeable of the water environment and the potential hazards (deep and shallow areas, currents, depth changes, obstructions, and where the entry and exit points are located). Never dive into an aboveground pool, the shallow end of any inground pool or headfirst into breaking waves at the beach. If you are bodysurfing, always keep your arms out in front of you to protect your head and neck. Summary Many drownings can be prevented by following simple precautions when in, on or around water (see Smart Moves: Preventing Water-Related Emergencies). Use the basic methods of reaching, throwing or wading to rescue or assist a person in the water without endangering yourself. If there is any chance that you cannot safely and easily help the person in trouble, call 9-1-1 or the designated emergency number immediately. Always call 9-1-1 or the designated emergency number for a person involved in a drowning incident as potentially fatal complications can develop later. Further training in water safety and lifeguarding is available through the American Red Cross. Think back to the water emergency in the opening scenario, and use what you have learned to respond to this question: 1. Knowing that the pool is deep where the child fell in, what is the best way to try to rescue the child? List the general care steps for a drowning victim who is unresponsive and breathing normally in shallow water. Figuring she did not hear you-after all, her hearing is not the best and she does not always wear her hearing aid-your friend uses the spare key she has to go inside. In the living room, you discover the real reason Grandma Mary did not come to the door. Explain how to observe an injured or ill child or infant, and how to communicate with the parents or guardian. Describe the signs and symptoms and care for common childhood illnesses and injuries. Describe four issues that can affect older adults and their implications for care. Explain how to communicate with and assist a person with a physical disability or mental impairment. Explain the options available when trying to communicate with a person when there is a language barrier. Child abuse: Action that results in the physical or psychological harm of a child; can be physical, sexual, verbal and/or emotional. Child neglect: the most frequently reported type of child abuse in which a parent or guardian fails to provide the necessary, age-appropriate care to a child; insufficient medical or emotional attention or respect given to a child. Responding to Emergencies 365 Pediatric, Older Adult and Special Situations Introduction In any emergency, you should be aware of the unique needs and considerations of the person involved. For example, children and infants, older adults, persons with disabilities and persons who speak a different language than your own have special needs and considerations that affect your approach to giving care. It is also important to know what to do if you find yourself in a crime scene or hostile situation. This chapter includes information to help you better understand the nature of an emergency and give appropriate, effective care. Children and Infants Children and infants have unique needs that require special care. At certain ages, children and infants do not readily accept strangers and may be very apprehensive. Very young children and infants also cannot tell you what is wrong and have difficulty expressing their feelings. Communicating with Injured or Ill Children or Infants We tend to react more strongly and emotionally to a child who is in pain or scared. You will need to try exceptionally hard to control your emotions and your facial expressions. To help an injured or ill child or infant, you also need to try to imagine how the person feels. This includes being injured or ill, being touched by strangers, and being separated from their parents or guardian. Depending on the age of the child, it may be necessary to direct questions about the situation to the parents or guardian. Communicating with Children Who Have Special Healthcare or Functional Needs When communicating with children and parents or guardians, remember to observe the whole situation and ask questions to determine if the child has special physical, developmental or functional needs. Generally, the parents and guardians can give you the best information since they are the most familiar with any medical equipment needed by the child. Do not assume the child has a mental disability because they are unable to express thoughts or words. Responding to Emergencies 366 Pediatric, Older Adult and Special Situations Communicating with Parents and Guardians If parents or guardians are excited or agitated during the emergency, the child is likely to be, too. When you can calm the parents or guardians, the child will often calm down as well. Remember to get consent to give care from the parent or guardian of the child when possible. Any concerned adults need your support, so behave as calmly as possible, explaining what you intend to do at each step. Characteristics of Children and Infants To be able to effectively check children and infants, it is helpful to be aware of certain characteristics of children and infants in specific age groups. Infants less than 6 months old are relatively easy to approach and are unlikely to be afraid of you. If you reassure the toddler that they will not be separated from a parent or guardian, the toddler may be comforted. A toddler may also respond to praise or be comforted by holding a special toy or blanket. Children in this age group are usually easy to check if you use their natural curiosity.