Illness Stages

In this study, phospholipid metabolism of cell membranes, high-energy phosphate metabolism, and intracellular free magnesium concentration in the prefrontal cortex of first-episode drug-naive schizophrenic patients and medicated schizophrenic patients at different stages of illness were compared with those of controls. Localized in vivo phosphorus 31 magnetic resonance spectra of the left dorsolateral prefrontal cortex of 11 drug-native, eight newly diagnosed medicated, and 10 chronic medicated patients with schizophrenia were compared with controls of similar gender, education, parental education, and handedness. Significantly decreased levels of phosphomonoesters in drug-native, newly diagnosed medicated, and chronic medicated patients and significantly increased levels of phosphodiesters in drug-native patients were observed when compared with controls. There were no significant differences in the levels of high-energy phosphate metabolites between the groups except for a significant decrease in the inorganic orthophosphate levels of newly diagnosed medicated patients. A significant increase in the intracellular free magnesium concentration was observed in drug-naive, newly diagnosed medicated, and chronic medicated patients compared with controls. There were no correlations between the patients' negative and positive symptoms and the observed phosphorus-containing metabolites. A reduction in precursors of membrane phospholipid are observed during the early and chronic stages of the schizophrenia illness, and breakdown products of membrane phospholipids are increased at the early stage of illness before medication treatment.

BackgroundThis article assessed maternal and neonatal outcomes amongst users of prevention of mother-to-child transmission (PMTCT) of HIV services in Addis Ababa, Ethiopia.ObjectivesThe study aimed to assess the health outcomes (antiretroviral prophylaxis versus antiretroviral treatment, CD4 counts, World Health Organization (WHO) stages of illness, other illnesses) of women who had used these services, as well as the HIV status of their babies and the infant feeding method adopted.MethodsA quantitative, cross sectional, retrospective cohort design was used. Document reviews were conducted with a sample of 384 mother-infant pairs (out of a population of 796) who had used PMTCT services.ResultsAll respondents were using prophylactic antiretrovirals or antiretroviral therapy, but some were on the wrong treatment based on their CD4 counts. The CD4 counts increased four times more for women on antiretroviral treatment than for those on prophylactic antiretrovirals. The WHO’s stages of HIV illness did not improve but deteriorated in some cases, and 52 other illnesses were recorded. Out of the 384 infants, 6.0% (n = 23) were HIV-positive. Most respondents opted for exclusive breast feeding but some used mixed feeding during the first six months of their infants’ lives, despite having received health education related to infant feeding options.ConclusionThe respondents’ improved CD4 counts were inadequate to improve their World Health Organization stages of HIV illness. Some babies received mixed feeding during the first six months of their lives and 6% of the babies were HIV-positive despite their mothers’ utilisation of PMTCT services.

Lyme disease is the most common vector-borne disease in the United States. A cluster of children in Lyme, Connecticut, who had unexplained arthritis was reported by one of their parents in the mid-1970s. Investigation of this "epidemic" of arthritis led to the description of "Lyme" arthritis in 1976 and ultimately to the discovery of its bacterial etiology. Both the reported incidence of the disease and its geographic range have increased dramatically in recent years. Perhaps even more striking has been the increase in publicity about the illness in the consumer media, which has been accompanied at times by near-hysteria about both its risks and its complications. This publicity,combined with a very high frequency of misdiagnoses in people whose symptoms are due to other causes, has resulted in a degree of anxiety about Lyme disease (among both patients and physicians) out of proportion to the morbidity it causes.Lyme disease is caused by the spirochete Borrelia burgdorferi, a fastidious, microaerophilic bacterium that replicates very slowly and requires special media to grow in the laboratory. B burgdorferi is transmitted by ticks of the Ixodid species—in the United States, primarily Ixodes scapularis (previously called Ixodes dammini), the deer tick. Lyme disease occurs most commonly in areas where deer ticks are abundant and where the prevalence of B burgdorferi in these ticks is high (20% to 50%)—southern New England, southeastern New York, New Jersey, eastern Pennsylvania, eastern Maryland, Delaware, and parts of Minnesota and Wisconsin. Lyme disease is rare in the Pacific states because although Ixodes pacificus (the Western black-legged tick)can transmit B burgdorferi, very few (<2%) of these ticks are infected with the organism. People who have increased occupational,recreational, or residential exposure to tick-infested woodlands and fields(the preferred habitat of ticks) in endemic areas are at increased risk of developing Lyme disease.The life cycle of Ixodid ticks consists of three stages—larva, nymph, and adult—that occur during a 2-year period(Fig. 1). Each stage feeds only once. The adult female lays eggs in the spring, and the larvae emerge in the early summer. They overwinter and emerge the following spring as nymphs. In the fall, the nymphs molt and become adults. The adults spend the winter on an animal host, a favorite being the white-tailed deer (hence the name, the deer tick). In the spring, the females lay their eggs and die, completing the 2-year life cycle.Most larvae (98%) are not infected with B burgdorferi because transovarial transmission rarely occurs. The larvae feed on a wide variety of small mammals (such as Peromyscus leucopus, the white-footed mouse) that are important natural reservoirs for B burgdorferi and thereby may become infected. A tick can acquire infection with B burgdorferi at each stage in its life cycle, so the proportion of adult ticks that is infected is higher than that of either nymphs or larvae. However, most cases of Lyme disease occur after the bites of nymphal-stage ticks because they are more abundant than adult ticks, they are more difficult to detect due to their small size, and humans frequently enter tick-infested habitats at times of the year when they are prevalent.A number of factors are associated with the risk of transmission of B burgdorferi from ticks to humans. First, a tick has to be infected to transmit the organism. The proportion of infected ticks varies greatly both by geographic area and stage of tick in its life cycle. I pacificusoften feeds on lizards, which are not a competent reservoir for B burgdorferi. Consequently, only 1% to 3% of these ticks, even in the nymphal and adult stages, are infected with B burgdorferi. By contrast, I scapularis feeds on small mammals that are competent reservoirs for B burgdorferi. As a result,in endemic areas, rates of infection of I scapularis are approximately 2% for larvae, 15% to 30% for nymphs, and 30% to 50% for adults. Infection rates as high as 60% to 90% have been reported in selected areas.Lyme disease occurs throughout the world. In Europe, most cases are seen in the Scandinavian countries and in central Europe (especially Germany, Austria,and Switzerland), although cases have been reported throughout the continent. The incidence of Lyme disease varies tremendously from region to region and even within local areas. Information about the true incidence of the disease is complicated by reliance, in most instances, on passive reporting of cases as well as by the high frequency of misdiagnosis. Further, studies have indicated that as many as 50% of patients who develop serologic evidence of recent infection with B burgdorferi may be asymptomatic.In 1995, 11,603 cases of Lyme disease were reported to the United States Centers for Disease Control and Prevention (CDC) by 43 states and the District of Columbia, which was the second highest number reported since surveillance began in 1982 (although it was an 11% decrease from the 13,043 cases reported in 1994)(Fig. 2). More than 75% of the reported cases occurred in just 63 counties(Fig. 3). In Connecticut, which has the highest incidence of Lyme disease in the United States, the reported annual incidence of Lyme disease in 1995 was 47.1/100,000 persons and varied from 7.5/100,000 persons in Hartford County to 129.7/100,000 persons in Wyndham County. In certain towns in which the disease is hyperendemic (eg, Lyme), the annual incidence may be as high as 1,000/100,000 persons or more. The incidence of Lyme disease is highest among children. The reported incidence among children 5 to 10 years of age in Connecticut in 1995 was 79/100,000 per year. Because not all cases of Lyme disease are reported, these figures undoubtedly are underestimates.B burgdorferi is transmitted when an infected tick inoculates the organism into the blood vessels of the skin of its host. The risk of transmission from infected deer ticks is related to the duration of feeding. It takes hours for the mouth parts of ticks to implant fully in the host and much longer (days) for the tick to become fully engorged. Experiments with animals have shown that nymphal-stage ticks must feed for 36 to 48 hours or longer and adult ticks must feed for 48 to 72 hours or longer before the risk of transmission of B burgdorferi from infected ticks becomes substantial. The duration of time that a tick has fed can be estimated from indices of engorgement derived from experiments with animals. Based on these indices, there is evidence that approximately 75% of persons who recognize that they have been bitten by a deer tick remove the tick fewer than 48 hours after it has begun to feed. Indeed, the majority of persons who develop Lyme disease do not recall a tick bite. Unrecognized tick bites probably are associated with greater risk because unrecognized ticks may feed longer. A history of a tick bite is an indication that the person is at risk and should not be assumed to be the only exposure.Like other spirochetes, B burgdorferi is a cylindrically shaped organism, and its cell membrane is covered by flagella and a loosely associated outer membrane. The three major outer-surface proteins,OspA, OspB, and OspC (which are highly charged basic proteins of molecular weights of about 31, 34, and 23 kd, respectively), as well as the 41-kd flagellar protein, are important targets of the immune response of humans. Differences in the frequency of certain clinical manifestations of Lyme disease in Europe and in the United States (eg, the greater frequency of neuritis in European patients) have been attributed to differences in the molecular structure of different strains of B burgdorferi.After B burgdorferi is inoculated by the tick into the skin, it begins to spread locally. The inflammation results in a single erythema migrans rash in approximately two thirds of patients who become symptomatic. Days to weeks later, the spirochete may disseminate via either the bloodstream or the lymphatics to many other sites, including the skin(almost 25% of patients develop multiple erythema migrans), eye, muscle,bone, synovial tissue, central nervous system, and heart. Although it may be possible to isolate the organism from cultures of tissue, the small numbers that are present and the fastidious nature of its in vitro growth makes recovery of the spirochete difficult. Nevertheless, B burgdorferi has been isolated from the blood or from tissue at all stages of the illness.The pathogenesis of the symptoms late in the course of Lyme disease appears to be related to long-term persistence of organisms in tissues. It is likely that relatively few organisms actually invade the host, but mediators of inflammation amplify the inflammatory response and lead to much of the tissue damage. The spirochete prefers cell surfaces, but it will adhere to a wide variety of cell types, which may explain why it can cause clinical manifestations in such a broad array of organ systems. Because the organism may persist in tissues for prolonged periods of time, symptoms may appear very late in the course of infection. The symptoms of Lyme disease are due to inflammation, mediated by interleukin-1 and other lymphokines, that is a direct result of the presence of the organism. However, in a small subset of patients who have refractory symptoms despite antimicrobial treatment (such as recurrent Lyme arthritis), the symptoms may have an immunogenetic basis. There is substantial evidence that patients who have a high prevalence of the HLA-DR2, DR3, and DR4 allotypes may be genetically predisposed to develop chronic recurrent Lyme arthritis long after the bacteria have been killed.The clinical manifestations of Lyme disease generally are divided into two stages: early and late. Early Lyme disease often is subdivided further into early localized and early disseminated disease. The usual clinical manifestations of the different stages of Lyme disease are shown in Table 1. The skin is the initial target organ for infection by B burgdorferi. The first clinical manifestation is the typical annular rash, erythema migrans. It usually occurs 7 to 14 days after the tick bite, although its onset has been reported as few as 3 days and as many as 4 weeks later. The rash may be uniformly erythematous(Fig. 4)or it may appear as a target lesion with variable degrees of central clearing(Fig. 5). Occasionally there may be vesicular or necrotic areas in the center of the rash. The rash may be itchy, painful, or asymptomatic and may be accompanied by systemic symptoms, such as fever, myalgia, headache, or malaise. If the patient is not treated, the rash gradually expands (hence,the name "migrans"), sometimes to more than 1 ft in diameter. It will persist for at least 1 to 2 weeks and usually for longer. Approximately two thirds of children who have Lyme disease will have single erythema migrans.A substantial proportion of children (nearly 25%) in the United States who are acutely infected with B burgdorferidevelop multiple erythema migrans lesions, a manifestation of early disseminated disease that occurs approximately 3 to 10 weeks after initial infection. The secondary skin lesions, which may develop several days or even weeks after the first lesion, are smaller than the primary lesion. Fever and myalgia usually accompany the rash. Patients also may complain of headache, neck pain, or malaise, and conjunctivitis and regional lymphadenopathy may develop. Occasionally, when the erythema migrans rash resolves, new evanescent lesions, which usually are small (1 to 3 cm)erythematous annular lesions, appear and disappear over several weeks. These lesions may appear at different sites but generally do not expand.At this stage of the illness, aseptic meningitis may occur, although it is rare (about 1% of all patients). DNA of B burgdorferi has been found in the cerebrospinal fluid of patients at this stage of the illness. Focal neurologic manifestations, specifically cranioneuropathies, also may occur. Seventh-nerve palsy (facial palsy) is relatively common, affecting about 3% of children, and may be the presenting as well as the only manifestation of Lyme disease. The palsy usually lasts from 2 to 8 weeks before complete resolution (with or without treatment). Rarely, the palsy may resolve only partially or not at all. Bannworth syndrome (meningopolyneuritis)has been reported more commonly as a manifestation of Lyme disease in Europe. Encephalitis, with or without focal neurologic signs, occasionally occurs.Arthritis is the classic manifestation of late Lyme disease, occurring in about 7% of affected children. Patients who have arthralgia, a common, nonspecific symptom that frequently is present among patients who have early Lyme disease as well as those who do not have Lyme disease,should be differentiated from those who have objective evidence of synovitis(eg, an effusion), which is the hallmark of late Lyme disease. The arthritis occurs weeks to months after the initial infection. Primarily the large joints, especially the knee (which is affected in more than 90% of the cases), are involved. Although the affected joint is swollen and tender, the patient usually does not experience the exquisite pain that is typical of acute bacterial arthritis. Joint swelling generally resolves within 1 to 2 weeks (although it may last for several weeks) before recurring, often in other joints. Although the large joints are involved most commonly, any joint, including small ones, may be affected. If untreated, the episodes of arthritis often increase in duration, sometimes lasting for months. However,the disease usually resolves eventually, even in patients who are untreated and who have had many recurrences of arthritis. Most patients will not have a history of erythema migrans because those who have the rash usually are treated with antimicrobials and do not develop late manifestations of disease.Late central nervous system manifestations of Lyme disease(sometimes termed tertiary neuroborreliosis) rarely have been reported in children. In adults, chronic demyelinating encephalitis, polyneuritis, and impairment of memory have been attributed to Lyme disease, although there is controversy about the frequency with which such late manifestations occur,especially among patients who have been treated. Other very rare manifestations of late Lyme disease include acrodermatitis chronica atrophicans (a chronic, atrophic sclerotic lesion of the skin) and borrelia lymphocytoma, a localized, subcutaneous nodular lesion that usually occurs in either the earlobe or the breast.In the largest prospective study of children who had Lyme disease(a community-based study of 201 children in Connecticut), the initial manifestations of disease were: single erythema migrans (66%),multiple erythema migrans (23%), arthritis (7%), facial palsy (3%), aseptic meningitis (1%), and carditis(0.5%). Erythema migrans was more likely to occur on either the head or neck in younger children and on the extremities in older children,a finding similar to that recently reported from Europe. Only about one third of the children who had a single erythema migrans rash had positive serology for B burgdorferi at the time of presentation compared with almost 90% of the children who had multiple erythema migrans.More than 25% of the children had early disseminated Lyme disease at the time that they presented to a physician, and 89% had either single or multiple erythema migrans.Because clinical syndromes caused by congenital infection have been recognized with other spirochetal infections such as syphilis, the possible transmission of B burgdorferi from an infected pregnant woman to her unborn fetus has been of concern. Although case reports have been published in which B burgdorferi has been identified from several abortuses and from a few live-born children who had congenital anomalies, the placentas, abortuses, and tissues from affected children did not show histologic evidence of inflammation. In addition, no consistent pattern of congenital malformations (as would be expected in a"syndrome" due to congenital infection) has been identified. In two small longitudinal studies conducted by the CDC of pregnant women who developed Lyme disease, the adverse outcomes could not be attributed to infection with B burgdorferi. Furthermore, sero-surveys conducted in endemic areas found no difference in the prevalence of congenital malformations among the offspring of women who had serum antibodies against B burgdorferi and those who had no such antibodies.To assess the prevalence of clinically significant neurologic disorders attributable to congenital infection with B burgdorferi, two investigators conducted a survey of all pediatric neurologists in areas of the United States in which Lyme disease is endemic (Connecticut, Rhode Island, Massachusetts, New York, New Jersey, Wisconsin, and Minnesota). Of the 162 respondents to the survey (92%), none had seen a child who had a clinically significant neurologic disorder attributable to congenital Lyme disease or whose mother had Lyme disease during her pregnancy.There is no definitive evidence that B burgdorferi causes congenital disease, although the existence of such a syndrome also has not been excluded. If it does exist, congenital Lyme disease must be extremely rare. Finally, it should be noted that transmission of Lyme disease through breastfeeding never has been documented.The diagnosis of Lyme disease, especially in the absence of the characteristic rash, may be difficult because the other clinical manifestations of disease are not specific. Seventh-nerve palsy due to Lyme disease is indistinguishable from idiopathic Bell palsy, and Lyme arthritis may mimic either septic arthritis or pauciarticular juvenile rheumatoid arthritis. The clinical manifestations of Lyme meningitis may be difficult to distinguish from those of viral meningitis. Even the diagnosis of erythema migrans can be difficult because the rash initially may be confused with nummular eczema, granuloma annulare, an insect bite,ringworm, or cellulitis. However, the relatively rapid expansion of erythema migrans helps to distinguish it from these other conditions.Routine laboratory tests rarely are helpful in diagnosing Lyme disease because the associated abnormalities are nonspecific. The peripheral white blood cell count may be either normal or elevated. The erythrocyte sedimentation rate usually is elevated. The white blood cell concentration in joint fluid in patients who have Lyme arthritis may range from 25,000 to 125,000/mL, often with a preponderance of polymorphonuclear cells. When the central nervous system is involved, there usually is a with a of the of for B burgdorferi is and patients must an such as a or a to tissue or fluid for such tests are indicated only in rare including the that are on of of B burgdorferi have not been shown to be to be clinically studies in that is very Consequently, laboratory of Lyme disease usually on the of antibodies to B burgdorferi in the is well that the and of tests for Lyme disease The of is much than that of tests by that and the in the A study of the was conducted by the of and in with the In this and the CDC the (as by to of antibodies against B burgdorferi in of (with and to which the were The of the results in the laboratory with different as well as the of the results from different the were The of the of the from to and from to The investigators that with these for Lyme disease will result in a high rate of This is consistent with other reports of the of most tests for Lyme disease.The of Western the of serologic for Lyme disease. from the on of Lyme Disease in that a when tests for Lyme a either an or an and that result is positive or a Western to the If the or the is an is not The a of the concentration of antibodies against B burgdorferi. The about the of the that antibodies against of the spirochete are Most the presence of antibodies against at least either three or proteins of B least one of which is a more molecular outer for the to be tests are not for the diagnosis of early localized Lyme disease because only a of patients who have single erythema migrans will have a positive of tests very on the prevalence of the infection among patients who are because many including have the that nonspecific symptoms (eg, or may be manifestations of Lyme disease, parents of children who have only nonspecific symptoms frequently for Lyme disease tests for Lyme disease on such patients). Lyme disease will be the cause of the nonspecific symptoms in very of these children. However, because the of even tests for Lyme disease rarely 90% to of the tests in children who have no or symptoms of Lyme disease will be the majority of these will be Nevertheless, Lyme disease frequently is on these and such children often are treated with a patient has a positive serologic for antibodies to B burgdorferi, it is possible that Lyme disease may not be the cause of that In to the that the result is positive (a common the patient may have been infected with B burgdorferi and the symptoms may be to the infection. serum antibodies to B they may persist for many years despite treatment and clinical In addition, because a substantial proportion of people who become infected with B burgdorferi never develop symptoms, there will be a rate in endemic areas of When patients who had Lyme disease asymptomatic and untreated or clinically and develop any of symptoms and are for antibodies against B symptoms may be attributed to Lyme disease because of the positive should not tests for Lyme disease either for patients who have not been in endemic areas or for those who only nonspecific In the highly of certain proteins of B burgdorferi will become for in which will be more than for the treatment of children who have Lyme have been from studies of no clinical of treatment have been conducted among children. younger than years of age should not be treated with because it may cause of also is results with have been There is for new because the results of treatment with or have been so such as arthralgia, and myalgia may persist after a course of treatment for Lyme disease has been These nonspecific symptoms, which may accompany or more symptoms and of Lyme disease but almost never are the presenting resolve over several weeks. There is evidence that such symptoms are related to persistence of B burgdorferi, and there is no evidence that of antimicrobials their Because antibodies against B burgdorferi persist even after treatment of symptoms, there is no to tests of against B is a that Lyme disease is difficult to and that chronic recurrences are In the for treated children is The most common for treatment is the patient actually does not have Lyme In a of children who were treated for erythema all were well and none had developed symptoms of late disease at a of more than 3 years later. In a prospective study of 201 children who had Lyme disease had either early localized or early disseminated all were clinically at a of years later. The long-term for patients who are treated for late Lyme disease also is Although arthritis does especially among patients who have the or most children who are treated for Lyme arthritis are Indeed, long-term of children with Lyme disease before its cause was recognized of either were not treated with antimicrobials or were treated years after the onset of indicated that the arthritis multiple even in children who never were treated. of investigators tests on children to 4 years after they were treated and found no evidence of any long-term of the infection. Other investigators who are a community-based study of the long-term outcomes of persons who have Lyme disease have found no evidence of impairment of normal in children 4 to 10 years after endemic areas it is very common for children to be bitten by deer bites often However, the risk of Lyme disease is 1% to even in areas in which Lyme disease is of the it is highly Consequently, the of antimicrobial (the of which is for persons who have been bitten by a deer tick is not a tick is tests such as the is not although it may important The for infection of humans of either a positive or a result is The may be positive even only very few organisms are Furthermore, the no about either the of the or the duration of both of which may be of the risk of In addition, and results are more to Lyme disease is to (such as long when tick-infested areas and to for and remove ticks after time in such areas. may but they may be from the skin, and frequently or in large may significant especially in have to develop an against Lyme disease. against outer A against Lyme disease in animal proteins have been developed and are being in in humans. Because the spirochete in ticks and in stages of illness but not at the time of initial infection in is that the by the tick blood during before it inoculates the spirochete into humans. of B burgdorferi occurs in the tick. Even the is found to be it likely will be because the risk of disease is in most and outcomes among persons who the disease are rare. that other are being

Suicidal thoughts are highly prevalent among individuals with psychotic disorders and individuals at risk for psychosis. Although a growing body of literature demonstrates that this risk is greatest during the earliest stage of psychotic illness, few studies have directly compared rates of suicidal thoughts and behaviours across stages of illness. The current study addressed this gap by using a retrospective chart review to compare rates of past 2-week suicidal thoughts and past year suicidal behaviour across individuals at clinical high risk for psychosis (CHR-P; n = 50), first-episode psychosis (FEP; n = 84) and longstanding psychosis (LP; n = 59). Chi-squared analyses were used to compare groups on past two-week suicidal thoughts and past year suicidal behaviour. Frequencies of the various methods for suicidal behaviour were computed across the entire sample and within each group. Results indicate that individuals at CHR-P had the highest rate of past two-week suicidal thoughts compared to FEP and LP. The most common method for suicidal behaviour in all groups was overdose. These findings suggest that CHR-P is a particularly vulnerable period for suicide risk and highlight the continued need for research and resources for this population. These findings also underscore the importance of careful monitoring of medication use and efforts to reduce the risk of overdose.

Psychopathology in 90 consecutive human immunodeficiency virus-seropositive and acquired immune deficiency syndrome patients with mostly intravenous drug use history

The Interface Between Psychiatry and Palliative Medicine

Alcohol use disorder and circulating cytokines: A systematic review and meta-analysis

The sexuality of older adults at advanced stages of illness, or at the end of life, remains a taboo topic that is rarely addressed in the literature and in practice. As a result, the knowledge base informing the support needs of older adults at the final stages of life with regards to sexuality remains scant. The present study seeks to explore experiences of sexuality in older adults with serious illness or receiving palliative care, focusing specifically on the place of sexuality in their lives, the forms of sexuality expressed, and the challenges this population may face regarding their sexuality. The study is based on an interpretive qualitative design and relies on individual semi-structured interviews conducted with 10 older adults, between the ages of 69 and 86, who were receiving services from a palliative care program. The interpretive analysis of transcribed data generated two divergent themes that appeared to represent participants’ overall experiences with sexuality: “Sexuality excluded from life” and “Intimacy and sexuality integral to life”. While the analysis suggests that a distancing from sexuality can occur at advanced and terminal stages of incurable illness, it also suggests that sexuality does remain an important part of life for some older adults at advanced stages of a condition. The analysis further revealed a diversity of sexual expression which included, intimacy, genital sexual practices, and sexual thoughts and fantasies. The study contributes to the deconstruction of ageist and ableist biases by contesting the desexualization of older adults at the terminal stage of illness or at the end of life. The findings highlight the importance of acknowledging and addressing the sexuality of older adults in palliative care settings and in research.

Eating disorders represent a complex category of conditions, characterized by dysfunctional thoughts and behaviours about food and body weight or shape, heterogeneous clinical presentations, diagnostic migration and comorbidity. Such complexity highlights the limitations of conventional classification systems, which overlook clinically relevant eating-disorder characteristics such as illness progression. The clinimetric staging model presents an alternative conceptualization that may help differentiate stages of eating-disorder illness by focusing on clinically-relevant but often neglected illness characteristics and comorbidities. A novel statistical approach, namely network analysis, may facilitate the identification of specific eating-disorder stages. Network analysis has been widely applied to model psychiatric conditions as networks of interacting symptoms; this approach is particularly useful for examining the complexity of eating disorders. This study applied network analysis to explore the characteristics of eating disorders across healthy, at-risk, acute, and clinical populations by modelling symptom networks and comparing their structures. The findings reveal that clinically-significant eating disorder manifestations extend beyond eating-related symptoms and body weight or shape cognitions. In particular, the results underscore the importance of well-being and transdiagnostic dimensions in various populations, excluding clinical groups where symptoms of eating disorders predominate. Despite the intricacies of establishing a full staging model for eating disorders, the results obtained provide relevant information regarding clinical manifestations of eating disorders at different levels symptom intensity. This supports not only the development of a more refined staging model for these conditions, but also provides potential prevention and clinical targets for stage-specific interventions.

Part of the challenge in research on degenerative neurologic disease relates to distinguishing those measurements that essentially describe patient characteristics stable across the course of illness (traits) from those that vary systematically within subjects (states), particularly those specifically related to stage or duration of illness. A components-of-variance approach was used to examine the state versus trait aspects of the Alzheimer's Disease Assessment Scale (ADAS) Cognitive and Noncognitive subscales, a clinical instrument frequently used in research on Alzheimer disease. Subjects were 190 patients with probable AD followed longitudinally. Stage of illness was indexed by mental status scores. Analysis of variance was used to partition total variance into that associated with subjects (trait), stages (state: stage), subjects x stages (state: other), and error. ADAS Cognitive scores were strongly related to stage of illness (83% of true variance). ADAS Noncognitive scores were modestly related to stage (approximately 21% of true variance) and moderately related to state: other (47%). We discuss how state-trait analyses can be helpful in focusing attention on those areas of assessment most likely to accomplish specific objectives.

This study was undertaken to correlate the clinical features and pathologic changes noted during the initial and later stages of fatal typhoid illness. Five cases who died during the initial stage of the illness (< 2 weeks from onset) had altered mental status, tachypnea, and tachycardia. Three had shock and elevation of serum creatinine values. Autopsies of all five revealed hyperplastic Peyer's patches, features of adult respiratory distress syndrome, and megakaryocytosis. Five other cases died during the later stage of the illness (> or = 2 weeks after onset). They had a left shift in peripheral blood leukocyte count. Autopsies revealed deep ileal ulcerations with or without perforation and peritonitis and intercurrent pneumonia. Three of them had disseminated intravascular coagulation. Further studies are warranted to understand the mediators of shock and tissue injuries during the initial period of the illness.

Potentially severe and persistent or recurrent mental disorders pose the major threat to the health, happiness, and productivity of young people as they emerge from childhood to approach the threshold of adult life. The World Economic Forum has recently revealed that mental disorders now equal cardiovascular diseases (CVDs) as the major threat among noncommunicable diseases to the gross domestic product of modern economies.1 This is due largely to the timing in the life cycle of the onset of mental ill health,2 with 75% of disorders emerging by age 25. Universal or primary prevention is the ultimate solution and must be actively researched and pursued where it works, though it is difficult to assemble solid evidence for this.3 Where primary prevention is still out of reach (and the severe mood and psychotic disorders is one such domain), given we have a range of effective treatment strategies in psychiatry, there are 2 alternative pathways to actively follow.First, we must substantially extend the coverage of current interventions so that the vast majority of people who can benefit from mental health care can gain access. Currently, even in wealthy developed nations, only a minority of people with a mental disorder and a consequent need for care actually receive it, and in developing countries access is minimal and quality of care poor. This is why we need to support the global campaign for mental health.4·5 Second, timing is crucial, and early intervention offers the best hope for disease modification and the reduction of the widespread psychological, social, and economic impacts of treatment delay and poor quality care.6 This strategy is a cornerstone of mainstream health care, in cancer, diabetes, and CVD, yet early intervention or pre-emptive psychiatry7·8 has only recently been extended, deployed, and now widely endorsed within the mental health field. Even so, and somewhat surprisingly, a small yet diverse band of critics have not only questioned but also actively campaigned against early intervention concepts and reforms. Obviously such questioning is, to a significant extent, healthy and quite justifiable, being derived from a blend of genuine scientific conservatism, the late adopter phenomenon, and a valid fear of exposing patients to harmful stigma and overtreatment within traditional and narrow models of care, which can often do more harm than good and is more widespread than we care to acknowledge. However, the more extreme commentary on early intervention is evidence-poor and polemical, fueled by vested interests, apologists for the status quo of a narrow brand of traditional psychiatry, and, ironically, unreconstructed antipsychiatry. Nevertheless, we can take it as a positive that the tone and intensity of the debate indicates that real change and a genuine paradigm shift may be occurring. To succeed, it is crucial that early intervention remains strongly evidence-based.The frontier for early intervention is the prodromal or subthreshold stage of illness when a need for care is demonstrable yet the diagnostically clear or pathognomonic features of a particular syndrome or illness have not yet revealed themselves.9 The observation that such subthreshold or warning signs of future more severe illness, often lasting months or years, could be retrospectively identified was made more than 80 years ago by Sullivan10 and countless clinicians since then. The latter have usually experienced a sense of frustration that had they come on the scene during this more subtle phase, which turned out to be a prodromal stage of illness, perhaps it would have been possible to avert much of the patients' suffering and functional disturbance that subsequently ensued.10,11Careful research reconstructing the prodromal stage of psychotic illnesses'215 enabled the creation of operational criteria that could be used prospectively to identify a group of patients who proved to be at incipient risk of transition to psychosis. …

Clinical staging in psychiatry aims to classify patients according to the severity of their symptoms, from stage 0 (increased risk, asymptomatic) to stage 4 (severe illness), enabling adapted treatment at each stage of the illness. The staging model would gain specificity if one or more quantifiable biological markers could be identified. Several biomarkers reflecting possible causal mechanisms and/or consequences of the pathophysiology are candidates for integration into the clinical staging model of psychiatric illnesses. This review covers the evolution (from stage 0 to stage 4) of the most important brain functioning impairments as measured with electroencephalography (EEG), in psychosis spectrum and in severe mood disorders. The present review of the literature demonstrates that it is currently not possible to draw any conclusion with regard to the state or trait character of any of the EEG impairments in both major depressive disorder and bipolar disorder. As for schizophrenia, the most promising markers of the stage of the illness are the pitch mismatch negativity as well as the p300 event-related potentials, as these components seem to deteriorate with increasing severity of the illness. Given the complexity of major psychiatric disorders, and that not a single impairment can be observed in all patients, future research should most likely consider combinations of markers in the quest for a better identification of the stages of the psychiatric illnesses.

BackgroundIntensive case management (ICM) programmes for psychotic patients are effective in improving outcomes, but often unfeasible in resource-poor settings, as they typically require extensive human resources and expertise. We developed and evaluated the effectiveness of a less intensive case management program (LICM), led by community health workers, on one-year social functioning and service use.MethodsA prospective cohort study was conducted on patients aged 18 and above residing in a hospital catchment area. Outcomes were compared between LICM (n = 64) and non-LICM participants (n = 485). A counterfactual framework approach was applied to assess causal effects of the LICM on outcomes. The programme effectiveness was analyzed by augmented-inverse probability of treatment weighting (AIPW) to estimate potential outcome mean (POM) and average treatment effect (ATE). Outcomes were employment status and use of emergency, inpatient and outpatient services. Analyses were stratified by the number of previous psychotic relapse (≤ 1, > 1) to assess heterogeneity of treatment effect on those in an early and later stages of psychotic illness.ResultsIn the early-stage cohort, the likelihood of being employed at one year post-baseline was significantly greater in LICM participants than non-LICM participants (ATE 0.10, 95%CI 0.05–0.14, p < 0.001), whereas service use of all types, except outpatient, was not significantly different between the two groups. In the later-stage cohort, the likelihoods of employment between the two groups at post-baseline were similar (ATE -0.02, 95%CI -0.19–0.15, p = 0.826), whereas service use of all types was significantly higher in LICM participants.ConclusionLICM in a setting where community mental services are scarce may benefit those at an early stage of psychotic illness, by leading to better social functioning and no higher use of unscheduled services at the end of the programme, possibly through their better prognosis and medication adherence. A more intensive case management model may be appropriate for those in a later stage of the illness.

Molecular profiles of schizophrenia in the CNS at different stages of illness