N. Dennis. Connecticut College.
The diet is the principal source of such intake buy zantac 300 mg free shipping, with estimates of per capita daily consumption in Europe and North America exceeding 200 mg/day cheap zantac 300 mg online. Following oral administration buy zantac 150mg on-line, caffeine is rapidly and completely absorbed buy 150mg zantac otc, and it is then eliminated essentially completely (>95%) by metabolism. Such metabolism is complex, with at least 17 metab- olites being formed and excreted in the urine. However, these arise from three primary pathways that contribute to over 95% of the drug’s overall metabolic clearance; N-demethylation to form paraxanthine (80%), N1-demethylation to form theobromine (11%), and N7-demethylation to form theophylline (4%). C8-Hydroxylation and C8–N9 bond scission together account for the remaining 5% or so of caffeine’s metabolism. Accordingly, measurement of the in vivo probe’s oral clearance is the 592 Wilkinson gold standard by which this isoform’s activity can be evaluated. The caffeine may be given in the form of an available over-the-counter formulation or as a measured amount of coffee of known caffeine content or similarly as a cola drink. Some investigators have administered caffeine intravenously and used systemic clearance as the phenotypic trait measure (48,49). However, since caffeine is a low-clearance drug, the potential value of this approach is not particularly great and is outweighed by the disadvantage of administering the caffeine by intra- venous injection. Because caffeine is ubiquitous in the diet, phenotyping involves a caffeine-free period of one to three days prior to and also during the study period. However, if measurable caffeine is present in the plasma prior to administration of the in vivo probe, a pharmacokinetically based correction can take this into account (47). In addition, this phenotypic trait value is robust and reproducible when studied in the same subjects over a four-month period (50). In order to minimize the number of required blood samples, it has been suggested that estimation of caffeine’s elimination half-life based on three or four postabsorption plasma levels could provide an alternative phenotypic trait measure (51,52). Since caffeine’s volume of distribution is similar to total body water, such an estimate can also be used to obtain an approximate value of the probe’s clearance (48). This factor probably accounts for the lower accuracy and higher intrasubject variability found with foreshortened sampling protocols (49). Recently, a Bayesian estimation of caffeine clearance based on a single plasma level obtained at either 12 or 24 hours after intravenous administration of the probe was shown to be well correlated with the directly determined value (49). Caffeine is not extensively bound to plasma proteins; therefore, it readily distributes into saliva with a saliva:plasma concentration ratio of total drug between 0. Not surprisingly, therefore, a close correlation exists between saliva and plasma caffeine levels and derived pharmacokinetic parameters. Because of its noninvasiveness, even when sali- 1 vary flow rate is stimulated by chewing Parafilm or by the application of citric acid to the tongue, a large number of samples may be obtained for pharmacokinetic analysis, and collection can be extended beyond the clinical setting. Indeed, comparisons of caffeine’s oral clearance values independently determined from plasma and saliva concentrations are essentially the same (47,53–55). In an attempt to further simplify the caffeine phenotyping test, a trait measure based on the plasma or salivary paraxanthine:caffeine concentration ratio between three hours and seven hours after administration of the probe has been suggested (56). Generally, labeling has been at the N-3 methyl position, since this is the site of the major pathway of caffeine metabolism; however, labeling of all three N-methyl groups (58) and N-7 labeling has also been investigated (59). The need for mass spectrometry-based analytical methodology in the case of stable-labeled caffeine is in most instances outweighed by the safety issue related to exposure to radioactivity associated with the use of radio- labeled carbon. Other than equipment requirements, the caffeine breath test is 13 simple to perform and for [ C]-(N-3-methyl) caffeine, a commercial kit is available for this purpose. Typically, exhaled breath is collected at several intervals up to one to eight hours following an oral dose of labeled caffeine. The caffeine breath test appears to be reproducible, although extensive testing of this characteristic has not been reported. Early studies demonstrated the feasibility of this approach and its potential application to evaluating hepatic function (65,66). No extensive validation was attempted, so it is difficult to determine how well this test reflects the enzyme’s intrinsic clearance, rather than perhaps some other determinant, such as liver blood flow. However, the situation appears to be moot since phenacetin is no longer an approved drug worldwide because of its renal side effects following chronic dosing; accordingly, further studies of this approach are unlikely. These metabolites account for about 20%, 40%, and 15%, respec- tively, of the urinary recovery of caffeine-derived products. In addition, approxi- mately 10% of 17X is excreted unchanged and another 20% is hydroxylated to form 1,7-dimethylurate (17U). Theobromine (37X) is in part excreted unchanged (10%), and about 20% is metabolized to 3-methylurate (37U) and approximately 50% to 7-methylxanthine (7X). About 10 to 15% of theophylline (13X) is excreted into urine, with about 50% of this primary metabolite being metabolized to 1,3-demethylurate (13U) and some 23% to 1U. Finally, a small amount of caffeine is excreted unchanged in urine, and some additional minor metabolites are formed (45,51). Thus, the metabolism of caffeine results in a complex urinary recovery profile involving multiple primary and secondary metabolites as well as unchanged drug. A major difficulty in the application of these phenotypic trait measures is that they are essentially all empirical, and until recently their limitations were not understood or, more importantly, appreciated. A rigorous sensitivity analysis based on a phar- macokinetic model of caffeine’s metabolism and urinary excretion profile identi- fied a number of confounding variables that contributed to this situation (51). Experimental investigations have subsequently confirmed these theoretical findings. For example, significant correlations were obtained between Ratio 4 and caffeine’s oral clearance (r ¼ 0. As a result, con- clusions drawn from the interpretation of such flawed data may be inaccurate. Moreover, numerous studies based on the determination of caffeine’s plasma clearance in large numbers of subjects have not provided any evidence of discrete subgroups with either low or high values within a log- normal distribution. Modeling analysis also indicates the likelihood that the polymodal distribution could be an artifact (51); this is supported by the observations that despite the fact that the frequency distributions of Ratio 4 and caffeine clearance were unimodal, the distribution for Ratio 2 in the same subjects was bimodal (70). The metabolism of theophylline (1,3-dimethylxanthine) is similar to that of caffeine but less complex (vide supra). However, potential analytical sen- sitivity problems and, more importantly, safety considerations do not suggest that theophylline has any advantage over caffeine for this purpose (86). The gold standard approach depends on determination of the drug’s oral clearance following a single phenotyping dose under dietary caffeine-free conditions. Alternatively, a caffeine breath test can similarly provide such within-subject information. Activity is localized mainly in the liver; however, extrahepatic distribution is also present, especially in the nasal epi- thelium and lung. The 7-hydroxylation of coumarin (1,2-benzopyrone) is a major urinary metabolic pathway that accounts for about 60% of an orally administered dose (102). The phenotypic trait measure is simply the percentage of a 5-mg dose of coumarin excreted in urine as 7-hydroxycoumarin over the zero- to two-hours period following oral administration in the fasted state (102). Because the 7-hydroxy metabolite is excreted mainly as a conjugate, urine is pretreated with b-glucuronidase prior to analysis, and a methodology based on chromatographic separation would appear to be preferable to one using solvent extraction (103). Application of this phenotyping procedure to various population groups has shown that the trait measure exhibits considerable interindividual variability, and it is unimodally distributed in a normal fashion (102–104). Accordingly, it would be expected that in the general population all three phenotypes (extensive, intermediate, and poor) would be present. First, is the fact that the trait value is entirely empirical and has been validated and characterized to only a very limited extent. As expected, severe but not mild liver disease reduces the urinary recovery of 7-hydroxycoumarin, but, not unexpect- edly, renal dysfunction has also been found to affect the trait value (109). This is because of the extreme analytical difficulties associated with measuring plasma coumarin levels because of its relatively high volatility, and this problem is further compounded by the low dose used for phenotyping (5 mg). Coumarin is also excreted in the urine as a result of dietary and environmental exposure through fragrances and other sources. Such daily exposure may be as high as 25 mg (110), which probably accounts for the finding that in certain subjects the urinary molar recovery of 7-hydroxycoumarin exceeds the molar dose of cou- marin administered to determine the trait value (103,110). An additional con- sideration, especially in North America, is the absence of an available approved formulation containing coumarin, which was removed from the market 45 years ago because of its hepatotoxicity and carcinogenic properties in animals (111).
His blood test sug- gested parasites (high platelet count) and Fasciolopsis was found order zantac 150 mg mastercard. He acted quickly to clear up his Staph aureus infection by having a wisdom tooth pulled zantac 150 mg fast delivery. Later we noticed a common lung infection discount zantac 300mg visa, Pneumocystis discount 150 mg zantac with mastercard, but he still could not stop smoking. At the last visit he had picked up the intestinal fluke again, probably from eating rare meat but he had no solvents in his body. This explains why the parasite stayed in the intestine and did not move to his liver or lungs. This bout with lung cancer was missed by his medical doctor whom he continues to see regularly. Perhaps if his medical doctor had also seen the cancer, he would have quit smoking. He and his wife have been neglectful of the parasite program and other restrictions. Richard England Lymphoma In Bone Richard England has 2 preschool children and a wife who brought him here. Due to his resentment at being “dragged” in by his wife, I tested only for Fasciolopsis and Sheep liver fluke. His young children sat quietly in their chairs during the appointment, sensing the grave danger their father was in. But he made jokes about my technical com- petence and devices instead of listening. A friend who had gone through our cancer program successfully tried to encourage him at home. He was always talking about his exceptional oncologist and the great rapport and team work in the hospital. His wife would have gladly moved from their fossil fuel contaminated home or turned the furnace off and put in an electric space heater till they could sell the home. So I began with a conversation with her husband in the office instead of with her. The chronology of her illness was: 6 months ago she had arthritis; 3 months ago it became more serious; 1½ months ago walking was very painful; 1¼ months ago she needed a walker; 4 weeks ago she could not walk. Her clinical doctor diagnosed rheumatoid arthritis and treated her with a steroid. They put steel reinforcement in one leg and cut out the cancerous part in the other leg. She will have another week of this but her doctor let him know they could only expect a short remission, if any. I discussed my approach with her husband, reassuring him that I did not controvert any clinical treatment. She was using a walker and had visible pain, but she was interested in my approach. They have a lot of electronic equipment in house, but no copier; computer is on porch. She is wearing a metal partial denture; she will not wear it at night and change this to plastic soon. She has been using Efferdent for cleaning her teeth; she will switch to grain alcohol. She is not on any supplements except magne- sium (300 mg) 1/day and Vitamin B6 (500 mg) 1/day. Her friend who is cooking for her said she would eat only noodles with any enjoyment. We are adding Vitamin D, prescribed by dentist (50,000 u) 1/day for 30 days for pain and to help healing. She thinks the kidney herbs were instrumental in her suddenly feeling “like my old self. We are now starting a regimen of: 6 caps per week only; then 5 days/week; then 4 days/week; then 2 caps per week indefinitely. She is not using any as- sistance with walking and sits down easily on a chair by herself without discomfort. One week later She is not using her cane and is sitting comfortably on a chair without a cushion. Start on 07 (a commercial preparation of chlo- rine dioxide) and peroxy (17½ % hydrogen peroxide). Her husband and friends supported her and were not negative about alternative therapy. She had a particularly difficult time killing all the parasite stages but pursued the program diligently without being discouraged and quitting. She has had kidney infections (pain over kidney, frequency of very yellow urine, dizziness, ears are shut). Hopefully, she will continue to work on her health and clear her,, remaining parasites. Half a year later She had all metal removed from her mouth but got a severe infection afterward. She will avoid eating solvent-polluted food and products and using solvent- polluted products and go back on the parasite program. Her com- plaint is bloating and gas, loss of bowel control, and pain across the mid- abdomen. She has stayed on their herb recommendations and been health conscious ever since. She asked whether she should risk expanding her food list now that her pain and diarrhea are gone. One week later She can eat cheese and applesauce again, her favorite foods, without pain. Potassium very low radon in adrenals She will live with son for a while to clear radon from her body. Summary: This very pleasant woman apparently recovered from bone cancer decades ago! A case like this should have been followed by the National Cancer Institute to verify all the facts and not miss finding out what was responsible for her survival. She has no kidney stones and only one additional parasite: possibly the herbs, whose names she had forgotten after she threw them out recently, kept her free of parasites and also kept her youthful! Go off caffeine and onto milk, 2 pints of water/day, citrus juice, freshly squeezed or fresh squeezed frozen. Summary: Debbie and her elderly mother who came with her were radiating joy at her last visit. Five days after starting the parasite-killing program all the malignancy was gone. She moved her bed to the other end of the house and the com- puter-room door was kept closed Her husband was supportive. She complied immediately with all the changes recommended She is inter- ested now in learning to make home-made cosmetics. She was so happy to have her life returned to her, she feels radiant and full of plans for the future. She chokes and coughs, especially in damp weather, asthma-like; a lot of laryngitis. She said she had skin biopsies done by a derma- tologist in Illinois about one year ago, taken from the red big blotches on her skin. We did not see her again but trust that she would hurry back if a new problem occurred. Pleural biopsy showed adenocar- cinoma (scattered malignant clear cell carcinoma). They will take their laundry to a commercial laundry to dry and not use clothes dryer nor hair dryer. I made the mistake of thinking he would certainly return in a few days for his appointment and we would get him started on his parasite program then.
Dose in hepatic impairment: in patients with a Child--Pugh Class A or B use the standard loading dose but half the maintenance dose discount zantac 300 mg visa. Discard the vial if the vacuum of the vial does not pull the diluent into the vial purchase zantac 150mg with amex. Withdraw the required dose and add to a suitable volume of compatible infusion fluid to give a solution containing 0 order zantac us. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present discount zantac online master card. Displacement value 1mL/200mg Stability after preparation From a microbiological point of view, should be used immediately, however: * Reconstituted vials may be stored at 2--8 C for 24 hours. Monitoring Measure Frequency Rationale Infusion-related Throughout therapy * Flushing and nausea are the most common -- if reactions severe consider stopping treatment. Development of a * Although rare exfoliative cutaneous reactions may rash occur, e. Serum amylase or * Patients with risk factors for acute pancreatitis lipase should be monitored closely, e. Visual function * Visual acuity, visual field, and colour perception should be monitored if treatment lasts longer than 28 days. Significant * Efavirenz may "voriconazole levels or effect (or "side-effects): interactions Restrict doses of efavirenz to 300mg/day and double the voriconazole dose. Monitor for any toxicity and/or lack of efficacy when given with efavirenz or nevirapine. Low-dose ritonavir should be avoided also unless risk/benefit justifies the use of voriconazole. Phenytoin should be avoidedif possible -- if it cannot, monitor phenytoin levels and increase maintenance dose of voriconazole to 5mg/kg every 12 hours. Causes very large increase in sirolimus levels and may increase levels of ergot alkaloids (avoid). Ciclosporin dose should be halved, tacrolimus dose decreased by a third and levels monitored with dose adjustment as necessary (process reversed on ceasing voriconazole). Monitor blood glucose closely if taking sulfonylureas -- possible "levels causing hypoglycaemia. Visual perception may be altered/enhanced, blurred vision, colour vision change or photophobia occurs commonly -- effects are transient and fully reversible (usually lasting about 1 hour). This assessment is based on the full range of preparation and administration options described in the monograph. Prevention of maternal-fetal transmission: pregnant women (over 14 weeks of gestation) should be given 500mg/day orally (100mg five times per day) until the beginning of labour. Dose in renal impairment: adjusted according to creatinine clearance: * CrCl 10--50mL/minute: 1--2mg/kg every 8 hours. If it is not possible to monitor plasma zidovudinelevels, monitor for signs ofintolerance e. Inspect visually for particulate matter or discoloration prior to administration and discard if present. Zidovudine | 863 Technical information Incompatible with Meropenem Compatible with Flush: NaCl 0. Stability after preparation From a microbiological point of view, should be used immediately; however, prepared infusions may be stored at 2--8 C and infused (at room temperature) within 24 hours. Alternatively, recovery may be enhanced by brief (2--4 weeks) interruption of therapy, with marrow recovery usually observed within 2 weeks after which time therapyatareduceddosagemayberecommenced. Signs of immune * Inflammatory symptoms are more likely to occur in reactivation the first few weeks or months of initiation of syndrome therapy and should be evaluated with treatment instituted as appropriate. Significant * The following may "zidovudine levels or effect (or "side-effects): interactions fluconazole, ganciclovir (risk of profound myelosuppression, avoid combination if possible), probenecid, ribavirin ("risk of anaemia, avoid combination), valproate ("risk of haematological toxicity). Action in case of No specific antidote, management should be supportive as appropriate. This assessment is based on the full range of preparation and administration options described in the monograph. It inhibits bone resorption, but appears to have less effect on bone mineralisation. Pre-treatment checks * Do not give to patients already receiving other bisphosphonates. Women of child-bearing potential should take contraceptive precautions during planned treatment. Especially important in especially elderly patients and those receiving diuretic therapy. Table Z1 Dose adjustment in renal impairment Baseline CrCl (mL/minute) Zometa dose (mg) for prevention of skeletal-related events <30 Not recommended 30--39 3 mg 40--49 3. Inspect visually for particulate matter or discolor- ation prior to administration. Intermittent intravenous infusion (Zometa) The patient must be adequately hydrated using NaCl 0. Inspect visually for particulate matter or discolor- ation prior to administration. Zoledronic acid | 867 Table Z2 Volume of Zometa concentrate required Prescribed dose of Zometa (mg) VolumeofZometaconcentratesolution(mL) 4. Stability after From a microbiological point of view, should be used immediately; however, preparation opened vials (Aclasta) and prepared infusions (Zometa) may be stored at 2--8 C and infused (at room temperature) within 24 hours. Mg * Serum Ca may determine whether further treatment is necessary or appropriate. Additional information Common and serious Injection/infusion-related: Local: Injection-site reactions have been observed undesirable effects (redness, swelling, pain). Other: Renal dysfunction, asymptomatic and symptomatic #Ca (paraesthesia, tetany), pruritus, urticaria, exfoliative dermatitis, fever and influenza-like symptoms, malaise, rigors, fatigue and flushes (usually resolve spontaneously), arthralgia, myalgia, bone pain (may resolve on stopping treatment); eye disorders: uveitis, scleritis, conjunctivitis; jaw osteonecrosis (see above). Pharmacokinetics Excreted unchangedvia the kidney and taken up by bone inatriphasicprocess. Advise on importance of taking calcium and vitamin D supplements as prescribed where these are indicated. Advise patients with risk factors for osteonecrosis of the jaw (see Pre-treatment checks) not to undergo invasive dental procedures during treatment. This assessment is based on the full range of preparation and administration options described in the monograph. Zuclopenthixol acetate | 869 Zuclopenthixol acetate 50mg/mL oily solution in 1-mL and 2-mL ampoules This preparation must not be confused with the depot preparation. Pre-treatment checks * Do not give to patients in comatose states, including alcohol, barbiturate or opiate poisoning. If required, an additional injection may be given 1--2 days after the first injection. Technical information Incompatible with Not relevant Compatible with Not relevant (continued) 870 | Zuclopenthixol acetate Technical information (continued) pH Not applicable -- oily injection Sodium content Nil Storage Store below 25 C in original packaging. Monitoring Measure Frequency Rationale Therapeutic improvement Daily * To ensure that treatment is effective. Significant interactions * Zuclopenthixol may "risk of ventricular arrhythmias with the following drugs: amiodarone (avoid combination), disopyramide (avoid combination), erythromycin (avoid combination), moxifloxacin (avoid combination), sotalol (avoid combination). This assessment is based on the full range of preparation and administration options described in the monograph. Zuclopenthixol decanoate 200 and 500mg/mL oily solution in 1-mL ampoules This preparation is adepot preparation and must not beconfused with therapid-acting injection. Pre-treatment checks * Avoid in patients in comatose states, including alcohol, barbiturate, or opiate poisoning. Monitoring Measure Frequency Rationale Therapeutic improvement Periodically * To ensure that treatment is effective. Additional information Common and serious Drowsiness and sedation more common at start of treatment and at high doses. Significant * The following may "zuclopenthixol levels or effect (or "side-effects): interactions clozapine (avoid combination -- depot preparation cannot be withdrawn quickly if neutropenia occurs). If the patient is in shock, treatment with metaraminol or noradrenaline may be appropriate. Counselling Advise patients not to drink alcohol, especially at the beginning of treatment. Zuclopenthixol decanoate may impair alertness so do not drive or operate machinery until their susceptibility is known. This assessment is based on the full range of preparation and administration options described in the monograph.
In this study buy zantac 150 mg on line, if a person reported use of blood pressure medication within the past week this was regarded as using antihypertensives for calculation of the risk score buy zantac 300 mg with mastercard. Diabetes classification was based on reported doctor’s diagnosis or current use of diabetes medication order zantac 300 mg otc. Occupational groups were classified into the following main 48 categories: executives 300 mg zantac with visa, white collar, blue collar, unskilled workers and farmers. Each person was classified according to the occupation practiced for the longest period (Fogelholm et al. Postmenopausal was defined as having no regular menstruation within the last 12 months. Depression was not directly assessed in the Finnish former elite athlete cohort’s 1985 questionnaire, but life satisfaction was measured with Allardt’s scale containing the items ”interestingness of life”, ”life happiness”, ”life easiness” and ”loneliness” (Koskenvuo et al. Life satisfaction has previously been shown to correlate with depression in this cohort (Bäckmand et al. The Finnish former elite athlete cohort is a prospective study as described earlier. All subjects who were alive at the start of the follow-up on January 1, 1985, who answered the baseline questionnaire, and were not deceased by cancer within the first two years of follow-up (between January 1, 1985 and December 31, 1986), who did not answer ”cannot say” to the sleep quality question, were not shooters, and also provided information on other variables of interest were included in the analyses (n=1660). For each person, a probability to belong to every latent class is estimated based on item- response probabilities for the measured variables, conditional on latent class. The highest probability for a person’s class membership describes the most likely latent class for this person. The number of latent classes represents the number of different subpopulation clusters in the sample (Collins and Lanza, 51 Material and methods 2010; Lanza et al. The class prevalence likelihoods also represent estimations of classification error (Collins and Lanza, 2010). Data on questionnaire items was assumed to be missing at random, and was handled within an expectation-maximization algorithm. The expectation- maximization algorithm produces full information maximum likelihood estimates for parameters (Lanza et al. The difference in G2 statistic was statistically significant, suggesting that measurement invariance could not be assumed to hold across genders. Due to high degrees of freedom in the models, the G2 statistic does not follow the chi-squared distribution and, consequently, the p-value for absolute model fit cannot be calculated (Collins and Lanza, 2010). Model entropy and identification percentage were also considered where entropy close to 1 and an identification percentage closer to 100% describes better 52 model homogeneity. Furthermore, information about average posterior probabilities for the latent classes, that describe class separation were also considered. Finally, the decision was also based upon the interpretability and prevalence of the latent classes. Likewise, based on above mentioned criteria, the choice of best chronotype model in the substudy I fell on the four class model. Here, to confirm the choice of the four chronotype classes, the distributions in midpoint of sleep, a suggested measure of chronotypes (Roenneberg et al. The four classes differed, as was expected, in their midpoint of sleep and this was regarded as additionally supportive for the choice of a four-class chronotype classification in substudy I. Personal identifiers and possible dates of emigration or death for the Finnish former elite athlete cohort were obtained from the Population Register Centre of Finland. The proportional hazards assumption for each exposure was tested for by including an interaction with time in crude, univariate models. In table 2 the item-response probabilities that can range from 0 to 1 in each latent class are shown for men and in table 3 for women, respectively. Within each latent class, a certain pattern of responses is most likely or very unlikely to occur, respectively. Between the latent classes, certain class-specific item-response probabilities characterize the specific classes as compared to the others. The “Physically inactive, poor sleepers” is the least prevalent, fourth Profile in men (4. For each Profile, the characterizing highest probabilities in all variables are bolded and in italic. Furthermore, if an item response probability distinguishes the Profile from the others, the value is bolded and highlighted. The third Profile in women is called “Occupationally active, unsatisfied evening type sleepers” (17. The “Physically inactive, short sleepers” is the least prevalent, fourth Profile in women (10. For each Profile, the characterizing highest probabilities in all variables are bolded and in italic. Furthermore, if an item response probability distinguishes the Profile from the others, the value is bolded and highlighted. Members in Profiles 1 and 3 were younger than members in Profiles 2 and 4, and they had on average more educational years than members in Profiles 2 and 4. Highest prevalence of current smoking, as well as the highest alcohol consumption was observed for members in Profile 3. No significant differences were observed in weight between members of the Profiles. Men ”Physically “Lightly ”Occupation ”Physically Results of active, active, ally active, inactive, statistical normal morning evening type poor testing for range types with short sleepers” differences sleepers” normal sleepers” between range sleep” Profiles Profile number 1 2 3 4 Age, mean 46. Members in Profiles 1 and 3 were on average younger than members in Profiles 2 and 4, they had more educational years, and consumed on average more alcohol than members in Profiles 2 and 4. Women ”Physically ”Lightly ”Occupational ”Physically Results of active, active, ly active, inactive, statistical good normal unsatisfied short testing for sleepers” range evening type sleepers” differences sleepers” sleepers” between Profiles Profile number 1 2 3 4 Age, mean (years) 45. As was expected, the corrected midpoint of sleep in the four latent chronotypes differed, as follows: morning types, 2:49 a. This model suggested a division of chronotype into five latent groups, where one “tired, more evening type” and one “rested, more evening type” were identified. The characteristics of the “tired, more evening types” (17%) included not that easy to get out of bed in the morning, to be somewhat tired and have a not that good alertness in the morning and rate one-self as more evening- than-morning type, whereas the “rested, more evening types” (28%) were characterized by having quite easy to get up from bed in the morning, to be somewhat rested, but not having that good alertness in the morning, to rate oneself as more evening-than-morning type. The three other classes that were identified by the 5-class chronotype model included “morning types”, “rested, more morning types”, and “evening types”. The “morning types” (23%) were characterized by high likelihoods of having very easy to get out of bed in the morning, to be very rested and alert in the morning, and to rate oneself as definitely morning type. The “rested, more morning types” (24%) were characterized by having quite easy to get up from bed in the morning, to be somewhat rested and have a moderate alertness in the morning, to rate oneself as more morning- than-evening type and prefer morning working hours. The “evening types” (8%) were characterized by not that easy to get out of bed in the morning, to be somewhat tired and having very poor alertness in the morning, to report oneself as definitely evening type and to prefer afternoon working hours. The mean corrected midpoint of sleep in the five latent chronotypes differed, as follows: morning types, 02:48 a. When participants in working life were studied, similar associations were observed. However, after adjustments for age, smoking, alcohol consumption and education, as compared to membership in the “Physically active, normal range sleepers” Profile 1, only the association of membership in “Physically inactive, poor sleepers” Profile 4 with high HbA1c remained significant (Table 6). In women, most associations between membership in Profiles and high cardiometabolic risk factor levels were observed for membership in Profile 2 and Profile 4, as compared to Profile 1, respectively (Table 7). In men the membership in Profiles 2 and 4 was associated with a significantly higher risk score than membership in the Profiles 1 and 3, in both age-adjusted and fully adjusted models. In women, the Framingham 10-year Risk Score was highest for membership in Profile 2, differing from all other Profiles also in the fully adjusted models. Throughout the models was also membership in Profile 4 associated with a significantly higher risk score than in Profiles 1 and 3. Nevertheless, the interaction between history of sports and sleep duration or sleep quality regarding mortality was not significant and neither in former athletes or referents the sleep duration nor sleep quality were independently associated with mortality. Small gender differences between the Profiles were observed, but mainly the Profiles had similar characteristics in men as in women. Studying the operationalization of chronotype in the population-based sample, it was observed that chronotype classes are characterized by differences in morning- and evening preference and also morning tiredness. These Profiles were estimated to comprise of 45% and 47% of men and women, respectively.