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Gout is the clinical m anifestation of hyperuricem ia purchase 20 mg cialis super active mastercard erectile dysfunction supplements. After transplantation order 20 mg cialis super active with visa impotence psychological treatment, cyclosporine can exacerbate hyperuricem ia, and severe gout can be problematic even in the presence of chronic immunosuppression. M anagement of gouty arthritis usually involves some com bination of colchicine and judicious use of short courses of nonsteroidal anti-inflammatory drugs. Concomitant administration of allopurinol and azathioprine can cause profound bone m arrow suppression and is avoided by m ost physicians who treat transplant recipients. Because the m etabolism of m ycophenolate m ofetil (M M F) is not dependent on xanthine oxidase, use of allopurinol in patients treated with M M F is relatively safe [39,40]. FIGURE 13-27 FIGURE 13-28 Photograph of gingival hyperplasia. Gingival hyperplasia occurs Post-transplantation diabetes m ellitus (PTDM ). PTDM com plicates in approxim ately 10% of transplant recipients treated with the course of treatm ent in 5% to 10% of patients on cyclosporine- cyclosporine. Its severity reflects the interaction of effective dental based im m unosuppressive therapy. It is m ore com m on in blacks hygiene, cyclosporine dose, and concomitant administration of calcium and in patients with a fam ily history of glucose intolerance. This com plication does PTDM often reflects the substantial steroid-related weight gain not seem to occur with use of tacrolim us, and com plete resolution that sometimes occurs after transplantation. The severity of PTDM of gingival hyperplasia has been noted with conversion from can be attenuated by weight loss and corticosteroid withdrawal, cyclosporine-based therapy [25,41]. In a m ulticenter trial, PTDM occurred with greater frequency among patients treated with tacrolim us, particularly blacks. Although PTDM resolved over tim e in alm ost half of affected patients (as doses of tacrolim us and corticosteroids were gradually reduced), PTDM rem ained m ore com m on in patients receiving tacrolim us [25,42,43]. Ralph Crowe, Bruce Julian, Catherine Listinsky, Birmingham for contributing many of the illustrations used in this Brendan M cGuire, Klaus M onckemuller and Colleen Shimazu. United States Renal Data System : 1996 Annual Data Report. Blackstone EH , N aftel DC, Turner M E: The decom pensation of tim e Bethesda, M D: The N ational Institutes of H ealth; 1996. Suthanthiran M , M orris RE, Strom TB: Im m unosuppressants: cellular concom itant inform ation. Kershner RP, Fitzsim m ons W E: Relationship of FK506 whole blood 28:159–172. Penn I: Cancers in cyclosporine-treated versus azathioprine-treated 35:115–246. Cam pana C, Regazzi M B, Buggia I, M olinaro M : Clinically significant 10. Penn I: Occurrence of cancers in immunosuppressed organ transplanta- drug interactions with cyclosporin. Cecka JM , Los Angeles: UCLA Tissue Typing Laboratory; 1995, 99–109. M assy ZA, M a JZ, Louis TA, Kasiske BL: Lipid-lowering therapy in virus–encoded sm all RN A (by the EBER-1 gene) in liver specim ens patients with renal disease. Cockfield SM , Preiksaitis JK, Jewell LD, Parfrey N A: Post-transplan- 29. A com parison of cyclosporine and conventional Transplantation 1993, 56:88–96. Curtis JJ: H ypertension following kidney transplantation. Am J virus transform ation-associated genes in tissues of patients with EBV Kidney D is 1994, 23:471–475. Gaston RS, Curtis JJ: H ypertension in renal transplant recipients. Tricontinental M ycophenolate M ofetil Renal Transplantation Study 32. Curtis JJ, Luke RG, Jones P: H ypertension in cyclosporine-treated Group: A blinded, random ized clinical trial of m ycophenolate m ofetil renal transplantation recipients is sodium -dependent. Am J M ed 1988, for the prevention of acute rejection in cadaveric renal transplantation. Sollinger H W , US Renal Transplantation M ycophenolate M ofetil Study converting enzyme in renal transplantation recipients with hypertension. Group: M ycophenolate m ofetil for the prevention of acute rejection in N Engl J M ed 1983, 308:377–381. Gaston RS, Julian BA, Curtis JJ: Posttransplantation erythrocytosis: stenoses or renal-artery stenosis in a solitary kidney. M anske CL, W ilson RF, W ang Y, Thom as W : Atherosclerotic vascular 35. Kidney Int 1997, com plications in diabetic transplantation candidates. Pereira BJG, Levey AS: H epatitis C virus infection in dialysis and 19. M anske CL, Thom as W , W ang Y, W ilson RF: Screening diabetic renal transplantation. Kasiske BL: Risk factors for accelerated atherosclerosis in renal trans- 325:544–550. Julian BA, Quarles LD, Niemann KM W : M usculoskeletal complications 22. Am J Kidney rejection: im m unologic and nonim m unologic risk factors. Bristol-M yers Squibb: H yperlipidem ia and atherosclerosis in organ hyperuricem ia and gout. N oble S, M arkham A: Cyclosporin: a review of the pharm acokinetic properties, clinical efficacy and tolerability of a m icrolesion-based 24. Grundy SM for the N ational Cholesterol Education Program : Second form ulation (N eoral). Jindal RM : Posttransplantation diabetes m ellitus: a review. H ricik DE, M ayes JT, Schulak JA: Independent effects of cyclosporine renal transplantation. Barry enal transplantation is the preferred treatment method of end- stage renal disease (ESRD). It is more cost-effective than is Rmaintenance dialysis and usually provides the patient with a better quality of life. Adjusted mortality risk ratios indicate a sig- nificant reduction in mortality for kidney transplantation recipients when compared with that for patients receiving dialysis and patients receiving dialysis who are on a waiting list for renal transplantation (Fig. The indication for renal transplantation is irreversible renal failure that requires or will soon require long-term dialytic therapy.

Cyclosporine cheap cialis super active 20 mg mastercard doctor for erectile dysfunction in ahmedabad, pred- Controversy over whether pregnancy accelerates graft loss nisone buy 20mg cialis super active fast delivery erectile dysfunction medications and drugs, and azathioprine are safe during pregnancy and are not Patients are advised to wait 2 y after transplantation before pregnancy associated with fetal abnorm alities. Lim ited experience exists with m ycophenolate m ofetil during pregnancy. Hypertensive Disorders in Pregnancy FIGURE 10-20 Developing nations Developed nations M ortality and hypertension. W orldwide, hypertensive disorders are a Sepsis major cause of maternal mortality, accounting for almost 20% of mater- 8% nal deaths. M ost deaths occur in women with eclampsia and severe Hemorrhage 20% hypertension (HTN) and are due to intracerebral hemorrhage. Embolism Sepsis 20% Other 40% 25% HTN Abortion 15% 17% Other HTN 25% 17% Hemorrhage 13% 100–800/100,000 12/100,000 (deaths, births) (deaths, births) Kidney Disease and Hypertension in Pregnancy 10. The one used Rapid weight gain birth, fetal growth restriction, prem ature most commonly in the United States is that Headache, visual disturbances, delivery, and long-term developmental prob- proposed in 1972 by the American College abdominal or chest pain lems secondary to prematurity. These com- of Obstetricians and Gynecologists and plications are more frequent when hyperten- endorsed by the National High Blood sion is due to preeclampsia. The distinction is made between the pregnancy-specific FIGURE 10-23 hypertensive disorder (preeclampsia, and the The diagnosis of preeclam psia is strength- convulsive form, eclampsia) and chronic ened when one or m ore of the risk factors hypertension that precedes pregnancy, which are present. H ypertension develops after 20 usually is due to essential hypertension. Although edem a is a greater risk for preeclampsia (20–25% ). This disorder may recur with disturbances, and abdom inal or chest pain each pregnancy (in contrast to preeclampsia, are signs of im pending eclam psia. FIGURE 10-24 CLINICAL FEATURES OF CHRONIC W om en with chronic hypertension are usually older and m ay be HYPERTENSION IN PREGNANCY m ultiparous. Although hypertension often is detectable before 20 weeks, in som e wom en the pregnancy-m ediated vasodilation is sufficient to norm alize blood pressure so that wom en with W omen are older, more likely to be multiparous stage 1 or 2 hypertension m ay have norm al blood pressures by Hypertension: present before 20 wk, or documented previous pregnancy the tim e of their first antepartum visit. The risk of preeclam psia is substantially increased in wom en with chronic hypertension. Blood pressure may be significantly lower or normal in mid pregnancy Risk of superimposed preeclampsia of 15–30% 10. AND CHRONIC HYPERTENSION In addition to proteinuria, which may occur late in the course of the disease, hyperuricemia, mild azotemia, hemoconcentration, and hypo- calciuria are observed commonly. Some women with preeclampsia Chronic hypertension Preeclampsia may develop a microangiopathic syndrome with hemolysis, elevated liver enzymes, and low platelet counts (HELLP). The presence of the Renal: HELLP syndrome usually reflects severe disease and is considered an Creatinine Normal Increased; increased indication for delivery. W omen with uncomplicated chronic hyperten- blood urea nitrogen, sion have norm al laboratory test results unless superim posed creatinine preeclampsia or underlying renal disease exists. Current evidence suggests that an underlying genetic pre- disposition leads to abnorm alities in placental adaptation to the m aternal spiral arteries that supply blood to the developing feto- Fetal placental unit. These abnorm alities in the m aternal spiral arteries syndrome (IUGR, IUD, prematurity) lead to inadequate perfusion of the placenta and m ay be the earli- est changes responsible for the m aternal disease. The m aternal dis- ease is characterized by widespread vascular endothelial cell dys- function, resulting in vasospasm and intravascular coagulation and, ultim ately, in hypertension (H TN ), renal, hepatic, and central ner- M aternal vous system (CN S) abnorm alities. The fetal syndrom e is a conse- syndrome quence of inadequate placental circulation and is characterized by (HTN, renal, CNS) growth restriction and, rarely, dem ise. Prem ature delivery m ay occur in an attem pt to am eliorate the m aternal condition. IUD— intrauterine death; IUGR— intrauterine growth retardation. Placental disease M aternal disease Abdominal implantation Vasoplasm Placental vascular lesions Intravascular coagulation Endothelial dysfunction Genetic susceptibility (maternal x fetal) Kidney Disease and Hypertension in Pregnancy 10. Cooper and coworkers also noted an increased incidence in relatives by m arriage (eg, daughter-in-laws), and Increased incidence observed in mothers, daughters, 10 instances in which the disease occurred in one but not the other m onozygotic twin. The m ode of Mode of inheritance unknown: inheritance of preeclam psia is not known. Several possibilities have been suggested, includ- Single recessive gene? Normal pregnancy Preeclampsia Fetus M other A B (placenta) (uterus) Cell column of Spiral arteries anchoring villus M yometrium Cytotrophoblast stem cells Decidua AV Fetal Uterine Basement stroma blood membrane vessels Syncytiotrophoblast M aternal blood FV space Invasion Zone I Zone II and III Zone IV Zone V A Umbilical artery Villus Intervillus space Umbilical vein FIGURE 10-29 (containing fetal (maternal blood) arteriole and venule) Transform ation of the spiral arteries. A, The process by which the m aternal spiral arteries are transform ed into dilated vessels in preg- nancy is believed to involve invasion of the spiral arterial walls by FIGURE 10-28 endovascular trophoblastic cells. These cells m igrate in retrograde Uteroplacental circulation in normal pregnancy and preeclampsia. The m echanism s involved in this com - walled m uscular arteries into saclike flaccid vessels that perm it plex process are only beginning to be elucidated. These m echa- delivery of greater volumes of blood to the uteroplacental unit. The arteries, therefore, (c) rem ain thick-walled and m uscular, the diam eters in the m yom etrial Tunica media segm ents being half those m easured during norm al pregnancy. Recently, it has been reported that in preeclam psia the invading cytotrophoblasts fail to properly express adhesion receptors neces- sary for norm al rem odeling of the m aternal spiral arteries. This failure of cytotrophoblast invasion of the spiral arteries is con- sidered to be the m orphologic basis for decreased placental perfu- Fully modified Partially modified Unmodified sion in preeclam psia. AV–anchoring villus; CTBs— cytotrophoblast cells; Decidua M yometrium B FV— floating villi. A m ajor unresolved issue in the Lipid peroxides Cytokines pathophysiology of preeclam psia is the m echanism whereby abnor- m alities in placental m odulation of the m aternal circulation lead to m aternal system ic disease. The current schem a, which is a hypothe- Endothelial cell damage Platelet aggregation sis, depicts a scenario whereby placental ischem ia leads to the release of substances that m ight be toxic to m aternal endothelial cells. The resulting endothelial cell dysfunction also results in increased platelet aggregation. These events lead to the widespread Thromboxane A2 ↑ system ic vasospasm , intravascular coagulation and decreased organ Serotonin, PDGF ↑ flow that are characteristic of preeclam psia. N O — nitric oxide; PGI2 ↓ Systemic PDGF— platelet-derived growth factor; PGI2— prostacyclin 2. NO ↓ vasoplasm Thrombin ↑ Endothelin ↑ M itogenic factors↑ (eg, PDGF) ↓ Organ flow Intravascular coagulation Kidney Disease and Hypertension in Pregnancy 10. Preeclam psia is a m ultisystem maternal disorder, with dramatic alterations in heart, kidney, circulation, liver, and brain. Interestingly, all of these abnorm alities resolve within a few weeks of delivery. A ↓ Plasma renin Finally, sodium retention NO/PGl S1 ↓ Aldosterone 2 Endothelin owing to renal vasocon- Relaxation Contraction striction m ay further Antiproliferation Proliferation ↑ Sympathetic nervous system S2 increase blood pressure. TX ET cAM P— cyclic adenosine Vascular smooth cGM P/cAM P muscle cells monophosphate; cGM P— cyclic guanosine monophosphate; 5-HT— serotonin; PThr— parathyroid hormone; FIGURE 10-32 S2— serotonergic receptors; H ypertension in preeclam psia. Although the m echanism of the increased blood pressure in preeclampsia is Thr— thombin TX— not established, evidence suggests it may involve multiple processes. A possible scenario involves the following: thromboxane; TXA — 2 decreased placental production of estrogen and progesterone, both of which have hem odynam ic effects; thromboxane A2. These processes m ay then result in alterations in platelet– vascular and Dubey; endothelial cell function, with decrease in vasodilators such as nitric oxide and prostacyclin and increased production with permission.

Oxygen diffuses from the tissue through the catheter into an 70 | Critical Care in Neurology electrolyte chamber where an electrical current is generated effective 20 mg cialis super active erectile dysfunction urologist. Brain tissue oxygen tension is normally lower than arterial oxygen tension (15-50 mmHg); whilst tissue CO2 is normally higher (range 40-70 mmHg) order cialis super active without a prescription erectile dysfunction vacuum device. The sensors are useful in monitoring local changes and trends in tissue oxygenation that might be missed by SjvO2 measurements. At present it is primarily used in severe head injury and poor- grade subarachnoid hemorrhage, and in conjunction with other monitoring modalities. The technique allows a continuous method of monitoring of regional tissue oxygenation and in particular, monitoring areas of high ischemic risk, and is a promising and reliable clinical tool. Direct measures of CBF: Measurement of injectable tracers that reach the brain after peripheral injection using signal intensity changes. Xenon-Enhanced CT: In this technique xenon, a diffusible agent is used. The patient inhales a mixture of 28% xenon and 72% oxygen for approximately 4 minutes after baseline CT scans are obtained. Sequential scanning of the same slices occurs during the inhalation period. The arterial concentration is proportional to the expired xenon concentration. Advantages are the relatively low cost and high ease of use. The downside is a high sensitivity to motion artifact (Andrew 2010). SPECT (Single Photo Emission CT): In SPECT scanning, the radioisotope technetium-99m (Tc-99m) is combined with hexamethylpropyleneamine (HMPAO) or ethyl cysteinate dimer. SPECT scanning has the advantage of being easy to perform. However, there are limitations with regards to assembly of the compound. MR Perfusion: “Dynamic Susceptibility Contrast Imaging” also called “first-pass” or “bolus tracking” MR perfusion imaging is based on rapid acquisition of MR signal intensity data from the brain during the injection of a contrast agent. Signal intensity- Neurocritical Monitoring | 71 time curves are generated for each pixel in the image then CBF is calculated. Noninvasive Monitoring Continuous measures of CBF by Transcranial Doppler Transcranial Doppler (TCD) is a noninvasive technique that calculates blood flow velocity in the cerebral vasculature. An ultrasound beam is reflected back by the moving bloodstream at a different frequency than it was transmitted (Doppler shift), and from the Doppler equation, the velocity of blood flow (FV) can be calculated. Changes in FV correlate well with changes in CBF, as long as the orientation of the transducer and the vessel diameter remain constant. It is used clinically to diagnose vasospasm, to test cerebral autoregulation, and to detect emboli during cardiac surgery and carotid endarterectomy (Moppett 2004). From the FV waveform systolic, diastolic, and mean velocities can be calculated. The mean FV in the middle cerebral artery (MCA) is usually 35-90 cm/s and correlates well with CBF. The FV can be influenced by age, being lowest at birth (24 cm/s), highest at age 4-6 years (100 cm/s), and then declining until the seventh decade of life (40 cm/s). FV is also 3-5% higher in females and increases in hemodilutional states. Technique for Insonating the Middle Cerebral Artery (MCA): The M1 branch of the MCA is the commonest vessel to be insonated, and is visualized through a transtemporal window with a 2 MHz pulsed Doppler signal. The anterior and posterior cerebral arteries can also be accessed through this window, whilst a transorbital approach allows access to the carotid siphon and the suboccipital route to the basilar and vertebral arteries. This reflects distal cerebrovascular resistance and correlates with CPP. Uses of TCD in Intensive Care Head Injury: Three distinct phases have been shown in severe head injury with regard to CBF and MCA FV. The use of TCD allows interpretation of the dynamic physiological changes seen in severe head injury, and in combination with other modalities allows perfusion and oxygenation to be optimized for the individual patient. The highest MCA FV recorded at any stage is an independent predictor of outcome from head injury, and the loss of autoregulation (calculated by regression of CPP on MCA FV) has also been shown to be a predictor of poor outcome from head injury. Subarachnoid Hemorrhage: Vasospasm occurs in approximately 50% of people with subarachnoid hemorrhage between 2-17 days post-event, and is associated with significant morbidity and mortality. TCD may be used to detect vasospasm by the increase in MCA FV associated with vessel narrowing. Spasm is also assumed to be occurring when blood velocity is Neurocritical Monitoring | 73 >120 cm/s. High MCA FV is associated with worse-grade SAH, larger blood loads on CT (assessed by Fisher Grade) and hence worse outcome (Steiger 1994). Near Infrared Spectroscopy While the criticism of jugular venous oximetry is that it is representative of global oxygen delivery, near infrared spectroscopy (NIRS) is a noninvasive technique that measures regional cerebral oxygenation. Light in the near infrared wavelength (700-1,000 nm) can pass through bone, skin, and other tissues with minimal absorption, but is partly scattered and partly absorbed by brain tissue. The amount of light absorbed is proportional to the concentration of chromophobes (iron in hemoglobin, and copper in cytochromes), and measurement of absorption at a number of wavelengths provides an estimate of oxygenation (Owen-Reece 1999). The probes illuminate a volume of about 8-10 ml of tissue and are ideally suited for use in neonates because of their thin skull, but have been used with success in adults. Advantages of this technique are that it is non-invasive, and provides a regional indicator of cerebral oxygenation. Its major limitation is its inability to distinguish between intra- and extra- cranial changes in blood flow. Electrophysiological Monitoring An electroencephalogram (EEG) is obtained using the standardized system of electrode placement. Practically, this is not often readily available and requires expert interpretation. The EEG is affected by anesthetic agents and physiological abnormalities such as hypoxia, hypoperfusion and hypercarbia. A number of methods have been developed to simplify and summarize the EEG data: – Cerebral Function Monitor (CFM): This is a modified device from a conventional EEG. It uses a single biparietal or 74 | Critical Care in Neurology bitemporal lead, and is processed to give an overall representation of average cortical activity. The bispectral index (BIS) is a dimensionless number statistically derived from these phased and power frequencies and ranges from 0 to 100 (100-awake, 60-unconscious, 0- isoelectric EEG). This technology was derived with normal subjects and is not readily transferable to the injured brain, but may have a use in guiding sedation and analgesia. Spectral Edge Frequency: Compressed Spectral Array: Raw EEG data is processed into a number of sine waves (Fourier analysis).

Weight status of children was defined by UK90 growth reference standards order cialis super active 20mg on line impotence treatment reviews. The analyses were based on the proportion of adults who were overweight or obese at the age of 50 years as a result of weight status at 9 and 13 years order 20mg cialis super active amex erectile dysfunction natural remedies, respectively. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 57 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Height and weight measurements were taken at birth, and at 1, 14, and 31 years of age. Data at 14 years were obtained from a questionnaire that was sent to participants, and follow-up data at 31 years (1997–8) were obtained from a questionnaire, a clinical examination or both. Adolescence (age 14 years) overweight was defined as a BMI ≥ 85th to < 95th percentile and obesity as a BMI ≥ 95th percentile. Adult BMI at 31 years was classified as follows: underweight (< 18. The analysis was restricted to individuals for whom BMI data were available for all measurement points (males, n = 2876; females, n = 3404). A cohort study of 8498 children aged 7–15 years participated in the 1985 Australian Schools Health and Fitness Survey. Of these, 4571 completed a follow-up questionnaire at age 24–34 years in 2001–5. Height and weight were measured in 1985, and self-reported at follow-up. The accuracy of self-reported data was checked for 1185 participants. Overweight and obesity in childhood were defined according to international standard definitions for BMI, and, in adulthood, as a BMI of 25–29. Summary The longitudinal studies identified here presented data on tracking of weight status from childhood into adulthood. The results presented for each of the identified studies indicate that childhood overweight/ obesity persists into adulthood, endorsing the broader evidence base which supports the use of childhood weight status as a strong predictor of adult weight status in a policy context (e. There were methodological differences between the included studies, for example the number of participants included in the studies, the ages at which authors predicted weight status to and from, prevalence of overweight and obese across the studies, the thresholds used to define weight status as a child, the centile categories used to describe the distribution of weight status, and the growth reference population. All studies have limitations; however, these are considered to be high-quality longitudinal studies. Data from each of these four longitudinal studies have been used to predict adult weight status by childhood weight status, represented in the form of transition probabilities across the defined child to adult weight status categories (Table 28). For stage 1 of the Exeter Obesity Model transition probabilities derived from the longitudinal data reported by Power et al. These probabilities were applied to the distribution of children at the start of the model, expected to be informed by the 24-month follow-up data in the HeLP study, in order to predict the expected distribution of the cohort by adult weight status at the age of 33 years. Although not specifically appropriate for sensitivity analyses, the estimate transit probabilities using data reported by Venn et al. Model development (stage 2): predicting the impact of overweight and obesity on incidence of weight-related health events Weight-related events Stage 2 of the model starts with a cohort of people with a given distribution by weight status (healthy weight, overweight or obese), as described in stage 1. Stage 2 uses CHD, stroke, T2DM and CRC as the weight-related health events of interest. The selection and inclusion of these four events is considered a conservative assumption (i. The selection and inclusion of these four events is based 58 NIHR Journals Library www. Of importance when identifying health events for inclusion in the model was the simplifying assumption in the model that once a person experienced a condition they were then not exposed further to additional events. This led to a focus on the main primary health conditions, rather than events such as hypertension, which, although relatively frequent (and serious), was considered to be analogous to an intermediate outcome increasing the future risk of events such as CHD, stroke and T2DM. Incidence (probability) of the weight-related health events was informed using a targeted keyword literature search (in MEDLINE) to identify studies that estimated the incidence of comorbidities related to obesity and overweight. The search strategy was structured using the following terms: (obesity OR adipose tissue OR body mass index OR body composition) AND (comorbidit$OR multimorbidit$OR chronic disease). No date limits or language restrictions were applied to the search. Eligible studies were systematic reviews of cohort studies, reporting risk estimates based on the incidence of weight-related events including T2DM, cardiovascular disease (including hypertension, coronary artery disease, congestive heart failure, pulmonary embolism, stroke and dislipidaemia) and CRC. Of these, only one was considered eligible for inclusion. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 59 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Twenty comorbidities were initially included in this analysis: cancer (kidney, colorectal, prostate, ovarian, uterine/endometrial, esophageal, pancreatic and postmenopausal breast), T2DM, cardiovascular disease (hypertension, coronary artery disease, congestive heart failure, pulmonary embolism, stroke and dislipidaemia), gallbladder disease, chronic back pain, osteoarthritis, asthma and sleep apnoea. For each of the weight-related events evaluated in Guh et al. We used these data to estimate the incidence of the events in the reference group (i. Using these raw data on incidence in the reference group, we then applied the risk ratios reported by Guh et al. Mortality data People are exposed to an annual mortality risk in each cycle of the model in stage 2. People in the disease-free state (no weight-related event) are subject to all-cause mortality risks based on age-specific data from the UK Office for National Statistics,89 using data reported for 2012–14, assuming a cohort of people with a gender ratio of 1 : 1. Data on mortality risks by health condition, whereby people are in health states defined by the weight-related health events, were informed by a targeted literature search of the published literature. We searched the literature using terms for the population of interest (i. T2DM, CHD, stroke and CRC) with terms for mortality rate using the MEDLINE database in December 2015. Table 30 presents the data that we have used to populate the model on mortality risks for the health events. For stroke and CRC, we have used a mortality input for year 1 of the event, together with a separate mortality parameter for subsequent years in that condition/health state. This structure on mortality data is consistent with the findings from the literature search. TABLE 29 Estimated incidence rate (probability) of adult weight-related events by weight status: cases per 1000 person-years Weight status Weight-related event HE OW OB CRC 0. The search method involved targeted keyword searching in MEDLINE (December 2015) for CHD, T2DM, stroke and CRC. In addition, we used the data reported in the model-based economic evaluations for obesity identified earlier (see Table 26).

F. Hogar. Mount Saint Mary College.