Miracle-dz/UniFAR-FTUs huggingface dataset:
First-episode psychosis: primary care experience and implications for service development

AIM AND METHODS To capture the local primary care experience of first-episode psychosis before developing a local early intervention in psychosis service. A survey of Northamptonshire general practitioners (GPs) using a confidential questionnaire was carried out. RESULTS Out of 284 GPs, 123 (43%) responded. General practitioners are unlikely to start treatment before referring to a specialist service: 63 GPs (51% of responders) start treatment in 10% or less of individuals with first-episode psychosis and 19 (15.5%) GPs start treatment in 75% or more before referring them to psychiatric service; 42 GPs (34%) refer those who request/accept a referral and 66 GPs (53%) refer all even if they refuse. Overall, 92 GPs (74%) agreed that an early intervention in psychosis service is needed and 77 (63%) GPs welcome having a mental health clinic in their surgery. CLINICAL IMPLICATIONS Individuals are more likely to accept referral to a psychiatric service if offered than to ask for it. People disengaging, stigma, the service being difficult to access/inappropriate and carers’ lack of knowledge about mental illness are the likely causes for delayed referral.
Novel biologic mechanisms of levosimendan and its effect on the failing heart

Background: Calcium sensitizers belong to a new class of cardiac enhancers that stimulate cardiac contractility without causing intracellular calcium overload or increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium sensitizer in the real clinical practice, produces greater hemodynamic and symptomatic improvement in patients with acute heart failure than traditional inotropes. Objective: To review the recent experimental and clinical evidence on novel biologic mechanisms explaining the pleiotropic effects of levosimendan on the failing heart. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to December 2007. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. Immunomodulatory and antiapoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal responses in acute heart failure, leads to cardioprotection, and beneficially intervenes in the progression of syndrome. Experimental data show that levosimendan exerts its cardioprotective effects through its antioxidant properties and seems to be a potent inhibitor of H2O2-induced cardiomyocyte apoptotic cell death. Clinical data demonstrate that levosimendan does not increase markers of oxidative and nitrosative stress, in contrast to placebo treatment, in advanced chronic heart failure patients. Levosimendan has also been shown to activate mitoKATP channels which are important mediators of ischemic preconditioning. Pharmacological modulation of KATP channels may prove beneficial in patients at risk of myocardial ischemia, particularly those requiring inotropic support. Conclusion: Pleiotropic effects of levosimendan appear to have important clinical and prognostic implications in acute heart failure syndromes and ischemic heart disease.
The Incidence of Diabetes Mellitus in Pregnant Women and its Outcomes between Pregnant Women with Diabetes Mellitus and Non-diabetes Mellitus at Maharat Nakhon Ratchasima Hospital

Objective: To study the incidence of diabetes mellitus (DM) in pregnancy and its outcomes between DM and non-DM pregnancies at Maharat Nakhon Ratchasima Hospital. Materials and Methods: Descriptive, retrospective study. Research duration was from May 1, 2009 – May 31, 2011. Comparison of the adverse outcomes between 340 DM with 1,023 non-DM pregnancies using statistic analysis methods: independent sample t-test, descriptive statistic analysis and logistic regression analysis at p-value 3,500 gm were statistically significant higher in non-DM group (p 3,500 gm.
SCOTT-BROWN'S OTORHINOLARYNGOLOGY, HEAD AND NECK SURGERY, 7TH EDITION M J Gleeson, ed Hodder Arnold 2008 ISBN 9780340808931 (HB) pp 3900 Price £395

Selection Proceedings of the 132nd Semon Club, Otolaryngology Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, 17 November 2006, Ricard Simo, Leslie Michaels, Steve Connor, E22 The above articles are published online and can be viewed by subscribers at http://journals.cambridge. org/jid_JLO BOOK REVIEWS 1017
Characteristics of the amiodarone-warfarin interaction during long-term follow-up.

PURPOSE Characteristics of the amiodarone-warfarin interaction during long-term follow-up were studied. METHODS Medical records from patients seen in the anticoagulation clinic at the Hennepin County Medical Center between April 1998 and March 2003 were retrospectively reviewed. Patients were included if they were older than 18 years, used the anticoagulation clinic as their primary clinic for anticoagulation therapy, and were receiving combined amiodarone and warfarin therapy for at least one month. The primary study endpoint was the occurrence of International Normalized Ratios (INRs) of >5 at any time during combined warfarin-amiodarone therapy. The secondary endpoint was the frequency of warfarin dosage changes. RESULTS A total of 70 patients met study inclusion criteria. Of these 70, 7 had amiodarone started before warfarin initiation. Of the 2434 INR values analyzed, 43% (n = 1043) were in the target therapeutic range, 34% (n = 820) were below target range, and 23% (n = 571) were above target range. A total of 102 INR values (4%) were above 5. The relative risk of having an INR of >5 for patients on concurrent warfarin and amiodarone versus those on warfarin alone was 1.366 (p = 0.005). INRs of >5 were most common during the first 12 weeks of combined therapy, with no subsequent large peaks evident. CONCLUSION Among patients treated in an anticoagulation clinic, INR values of >5 were most common during the first 12 weeks of combined therapy with amiodarone and warfarin and necessitated reduction in warfarin dosage. No other notable changes in INR or amiodarone or warfarin dosage occurred throughout the remainder of the 80-week study period.
Dementia Care and Occupational Therapy

There is an increase in cognitive impairment in populations in the developed and developing world as populations age, with over half the cases being caused by Alzheimer’s disease. The number of people with dementia is increasing globally, in line with the ageing profile of the population in each country. In the United Kingdom, it has been established that dementia costs more than cancer, heart disease and stroke put together (Dementia UK 2007). The recent report from the Alzheimer Society of Canada (2009) has reached a similar conclusion, which is that we need to do more. Very many countries are generating their national dementia strategies in response to this challenge. From my work internationally with health and social care workers, I have come to the conclusion that the most significant action we can take is to improve the personal effectiveness of each and every practitioner. Every occupational therapist needs to be thinking carefully of his or her own potential contribution. If the role of the occupational therapist in care for dementia is crucial, this requires a response from universities and colleges to increase the educational elements on dementia in undergraduate and pre-registration programmes. A Scottish survey indicated that there is not much practical input into programmes (Cunningham et al 2006). For example, on one issue alone, occupational therapists need to know much more about dementiafriendly design and technology, so that they can advise people with dementia and their carers on how to maximise their independence at home. Simple measures such as increasing the light levels can make a huge difference, but carers tell me: ‘We were never told … ’ The journey of two people with dementia, even with the same level of underlying pathology, can go in completely different ways. One can maintain independence till right before the end of life, and another can be ushered
Teriparatide in the treatment of osteoporosis.

PURPOSE The efficacy, safety, and cost of teriparatide in the treatment of osteoporosis are reviewed. SUMMARY Osteoporosis is a leading cause of fractures in women and men but is underdiagnosed and undertreated. Antiresorptive therapies (calcitonin, estrogen, bisphosphonates, and selective estrogen-receptor modulators) have historically been used to treat this condition. Teriparatide (recombinant human parathyroid hormone) is an anabolic agent labeled for use in postmenopausal women and men with osteoporosis who are at high risk for fractures. Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. Teriparatide is expensive but may be cost-effective in selected patients. CONCLUSION Teriparatide offers a therapeutic option for patients at high risk of an osteoporotic fracture and for patients who are intolerant of or unresponsive to antiresorptive therapy.
Special considerations for treatment of type 2 diabetes mellitus in the elderly.

PURPOSE The intensity and selection of therapy for the treatment of type 2 diabetes mellitus in elderly patients are discussed. SUMMARY Glycemic control is fundamental in diabetes care; however, as glycemic goals are approached, the risk of hypoglycemia increases. This risk is even greater in the elderly due to many predisposing factors, including renal insufficiency, polypharmacy, drug-drug interactions, comorbidities, irregular meal patterns, and infrequent self-monitoring of blood glucose. When deciding on the desired intensity of diabetes treatment, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular complications. Three large-scale, randomized controlled trials examining the effects of intensive versus standard glycemic control on microvascular and macrovascular outcomes in patients with type 2 diabetes have been published in recent years. In general, a glycosylated hemoglobin (HbA(1c)) goal of <7% is reasonable for most patients. A less-aggressive goal may be considered for patients at high risk of hypoglycemia or high risk of complications from hypoglycemia, as long as acutely symptomatic hyperglycemia is avoided. Chlorpropamide, glyburide, and rosiglitazone, which pose a great risk for hypoglycemia, should be avoided in the elderly. CONCLUSION In the absence of clear evidence advocating strict glycemic targets goal of <7% is for elderly patients, an HbA(1c) reasonable for most patients; however, the risk of hypoglycemic complications must be weighed against the potential benefit of reducing microvascular and macrovascular disease. Metformin may be used as first-line therapy, but chlorpropamide and glyburide, which pose a great risk for hypoglycemia, should be avoided in the elderly. Due to increased cardiovascular risk, use of rosiglitazone in the elderly should also be avoided.
Bioequivalence among three methods of administering pantoprazole granules in healthy subjects.

PURPOSE The bioequivalence among three methods of administering pantoprazole granules was studied in healthy subjects. METHODS In this randomized, open-label, three-period, crossover study, 25 healthy adults received a single 40-mg dose of pantoprazole granules with applesauce orally, with apple juice orally, and with apple juice administered via a nasogastric tube. Subjects were randomly assigned to one of six treatment sequences. Blood samples were collected within 2 hours before treatment administration on study day 1 and at 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours after treatment administration. Plasma pantoprazole concentrations were analyzed by a validated liquid chromatography-tandem mass spectrometry method. The plasma pantoprazole concentration-time data for each subject were analyzed using noncompartmental methods. The 90% confidence intervals (CIs) for the test:reference geometric mean ratio were calculated for the peak pantoprazole concentration (C(max) ) and area under the concentration-time curve (AUC). RESULTS Of the 25 subjects enrolled, 100% completed the study. The mean C(max) and AUC values were similar for the three administration methods. The 90% CIs for the ratios of the geometric means of the granules in apple juice orally (92.4-112.5%) and in apple juice administered through a nasogastric tube (102.7-125.2%), relative to the granules administered with applesauce orally, were essentially within the bioequivalent limits of 80-125%. No serious adverse events or study discontinuations occurred. CONCLUSION Three methods of administering pantoprazole delayed-release granules for oral suspension-with apple juice orally, with applesauce orally, and with apple juice through a nasogastric tube--were bioequivalent in healthy subjects.
Author's response

We have shown that a diet that is deprived of iron prevents ileitis in a mouse model of Crohn's disease (TNFdeltaARE mice). 1 In his comment, Buchman was concerned that we misinterpreted our findings, as he supposed that sulphate may be more important than iron in the development of colitis in our rodent experiments. Most importantly, according to the composition of the experimental diets used in our studies (diet C1000 and C1038, Altromin GmbH, Lage, Germany), the total amount of sulphate salts (magnesium sulphate, iron sulphate, manganese sulphate and copper sulphate) in the control diet is comparable with the amount added to the low iron-sulphate diet …
What Happens to Fructose in the Gut

There is a separate transport system for fructose in the intestinal brush border. Fructose absorption takes place by facilitated diffusion, independently of the presence of energy supply or sodium. Until recently, the human fructose absorption capacity has been considerably overrated. It has been demonstrated with breath hydrogen tests that a dose of 50 g (2 g/kg body weight in children) is incompletely absorbed by most people; some actually absorb only 5g. Glucose, however, strongly facilitates fructose absorption. Diminished absorptive capacity for fructose may become of clinical relevance in case of consumption of apple juice, pear juice, or beverages sweetened with high-fructose corn syrups, and in case of concomitant consumption of, for instance, sorbitol. Fructose (and sorbitol) may have an aetiologic role in the irritable bowel syndrome in adults, and in recurrent abdominal pain and especially chronic nonspecific diarrhoea (toddler's diarrhoea) in children.
Hyperinsulinemia, Insulin Resistance, and Blood Pressure

This article first deals with the definition and measurement of insulin resistance, and makes a distinction between primary and secondary insulin resistance. The closest proxy of insulin action, i.e., plasma insulin concentration, is then discussed together with its relationship with insulin action. The available epidemiological evidence, both from cross-sectional and longitudinal studies, is rather consistent in indicating an association between insulin levels and hypertension independent of obesity, glucose intolerance, and aging. A weak association between insulin levels and blood pressure has been found, in some series, even in normotensive, healthy individuals. However, there are marked interethnic differences in this association. So far, case-control studies have univocally confirmed the presence of insulin resistance in hypertensive patients as a group; pathophysiological experiments have shown that the skeletal muscle is an important site of such insulin sensitivity. Furthermore, it is clear that the insulin resistance of essential hypertension is selective for glucose metabolism, other actions of insulin being unaffected. The possible pathogenic significance of insulin resistance in essential hypertension is then discussed by focusing on the interactions between insulin and hemoynamics, particularly in skeletal muscle tissue. Finally, the fact that insulin resistance tends to cluster with abnormalities of blood pressure regulation, glucose tolerance and lipid metabolism is discussed in the context of atherosclerotic cardiovascular diseases. The cluster itself, and, possibly, hyperinsulinemia/insulin resistance, are potentially atherogenic; the clinical and therapeutic implications of this synergism are evident. (Hypertens Res 1992; 15: 67-75)
Photodynamic therapy for cancer of the pancreas

Background: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Aims: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. Patients: Sixteen patients with inoperable adenocarcinomas (2.5–6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. Methods: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. Results: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4–30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Conclusions: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.
How we can radically improve life for people with dementia

The Alzheimer's Society has developed a range of services including awareness campaigns, information for people with dementia and carers, peer support networks, dementia advisers and learning and education programmes. In our next article, Andrew Chidgey sets out the current evidence on dementia and advises on some of the big opportunities to change the quality of life for people with dementia. He also explains why the Alzheimer's Society has produced guidance on what commissioners need to consider when commissioning services for people with dementia.
TAP2 polymorphisms in Iranian patients with type I diabetes mellitus

Type I diabetes (T1D) is an immune mediated disease characterized by immune destruction of insulin producing pancreatic beta cells. This disease is associated with the human major histocompatibility complex (HLA) region of the genome. The presentation of self peptides by HLA class I molecules is defective in individuals with this disease and both TAP1 and TAP2 are potential contributors to this defect. The aim of this study was to identify the correlation between TAP2 polymorphisms and T1D in Iran. Five known coding regions of TAP2 gene (sites 379, 565, 651, 665 and 687) were typed in a casecontrol study of 87 Iranian patients with T1D and 104 control subjects by using the amplification refractory mutation system (ARMS) PCR technique. The polymorphisms examined in codon 379 and 687 differed in frequencies between patients and controls and there is not any significant difference in frequencies between diabetic patients and control subjects in other three examined sites. TAP2 A was the most frequent allele in Iranian subjects (51.9% in healthy subjects and 47.1% in diabetic patients). The next frequent alleles in our subjects were TAP2 G and B and the frequencies of other alleles (TAP2 C, D, E and F) were usually lesser than 10%. TAP2 D allele was not present in our population and TAP2 E allele was not present in our diabetic patients. In conclusion, the polymorphisms examined in codon 379 and 687 differed in frequencies between patients and controls. We can consider these polymorphisms in all suspected individuals with diabetes under 30 years old.
Advances in Carotid Artery Revascularization

Carotid stenosis is seen in about 10% of patients with ischemic stroke. Many studies have been performed that provide insight into the natural history, diagnosis, and optimal management of carotid disease. Both medical management and surgery have advanced to the point that patients and their providers have many options when considering treatment. Over the last several years, carotid artery stenting has been shown to be a viable treatment choice in selected patients. Both stenting and endarterectomy are superior to medical management alone in stroke prevention when patients are properly selected. In this article we try to review the most recent data regarding the two procedures in the treatment of carotid stenosis and also discuss the controversies in carotid artery revascularization.
Variation in pressure pain threshold correlates with rheumatoid arthritis disease activity, not with the inflammatory parameters

Background Pain is a chief symptom of rheumatoid arthritis (RA) indicating the disease flare. Variation in pain sensitivity with inflammatory load may assist in measuring the disease activity. Tender joint counts, one of the currently used pain measures, is more a measure of active joints rather than the pain. Although visual analogue scale (VAS) reflects the perception of pain, it does not indicate the true change in the pain. Aim To evaluate whether pressure pain threshold (PPT) represents disease activity by comparing it with DAS-28 and inflammatory markers like ESR and CRP. Materials and methods Twenty freshly diagnosed female RA subjects were recruited after careful exclusion of patients with fibromyalgia (FM). They were assessed for tender joint count, swollen joint count, visual analogue scale (pain/general health), ESR, and CRP during their three consecutive follow-up of six week intervals. PPT was measured using digital algometer at three pairs of joint areas (metacarpophalangeals, wrists and most inflamed joint) and at three FM tender point sites (sub-occipital, mid-trapezius and buttocks). Arithmetic mean of all areas (average PPT) and average PPT of FM points were calculated. The data was analyzed using Pearson correlation co-efficient, Deming regression analysis and correlation of change. Results Average PPT and PPT of most inflamed joint have moderate to large correlation with DAS-ESR and DAS-CRP. In contrast, small to trivial correlation with ESR and CRP was noted. Similar results were seen for FM tender point sites. Conclusion PPT at inflamed as well as at FM sites correlates significantly with DAS-ESR and DAS-CRP. It does not correlate independently with changes in inflammatory parameters ESR and CRP. PPT in conjuncture with DAS could be useful in routine clinical practice to measure the pain as well disease activity, in RA patients .