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A typical study in 1993 differences obviously influence age-specific preva- showed that 8% of those with back pain (or 3% of the lence studies order suhagra 100 mg on line erectile dysfunction treatment boston medical group. In this period generic 100 mg suhagra overnight delivery erectile dysfunction utah, 6% lost at least 1 day off age groups, but chronic pain increases with age (up work, with 1% off work for the entire 4-week period. Several painful conditions In a year, 8–20% of the population will have some which are more likely to occur in older people time off due to back pain. About half of the are relatively uncommon, and so tend to be underesti- lost working days are in short spells (averaging 6 days) mated in general surveys. The is joint pains and this reflects an increasing pathologi- longer a person is off work with back pain, the less cal load with advancing age. However, several pain Studies on risk factors for back pain have shown that syndromes actually decrease in frequency with age there is little difference between men and women. Work loss due to low back pain is commoner in lower social classes; how- ever, this may be related to manual work. Heavy man- Back pain ual work and perhaps driving and jobs involving exposure to whole body vibration, are risk factors for Back pain is a description rather than a diagnosis. There is an increased aetiology of back pain remains illusive, although it is prevalence of low back pain in smokers. What is clear is that it is common and that it causes Pain caused by cancer much disability and work loss. The estimated days of work loss caused by back pain in Britain in 1993 was Cancer is not a single disease and the prevalence of 52 million days, at a cost to the National Health pain varies widely between different types of cancer. Cancer causes pain by various mechanisms, including Most people will experience back pain at some time in involvement of bone, viscera or nerves. Studies show a point prevalence of 14–30%, prevalent in later stages of the disease and may be with a period prevalence over a year of about 40%. Lifetime lem is compounded by the fact that treatment may prevalence for sciatica is around 3–5%. It however is a ‘soft’ measure; disability and work loss is clear then that in any individual patient, whether being more reliable measures, with more utility. A study of all stages of the Cluster headache by contrast is rare, and five times disease in a cancer hospital found a prevalence of more common in males than females. However, studies of advanced cancer in hos- normally between the ages of 20 and 40. It that most commonly cause pain are: bone, cervix, oral is probably commoner than migraine, with a lifetime cavity, stomach, lung, genitourinary, pancreas and prevalence of around 80%, but prevalence decreases breast. Pain in acquired immune deficiency syndrome Neuropathic pain Pain is a major problem in patients with acquired immune deficiency syndrome (AIDS), particularly in Neuropathic pain is a mechanism-based diagnosis the later stages of the disease. In human immunodeficiency virus (HIV)-infected with diabetes, shingles, trauma or surgery, will develop patients in the early stages of the disease, the incidence pain, but others will not. Recent work in mice sug- of clinically significant pain has been reported at about gests there may be a genetic predisposition. But, in patients with AIDS the prevalence grad- valence of neuropathic pain in the population has ually increases as the disease progresses. In the early been quoted as 1%, but it varies with aetiology and stages pain occurs in around 45% of patients, rising to across different age groups. In a hospice herpetic neuralgia the overall incidence in patients who study, 93% of patients experienced pain in the last have had shingles is 9–34%. In diabetics, about 45% will develop There is evidence of under-treatment of pain in neuropathy over a 25 year course. Studies have shown that: chronic post-surgical pain varies according to the • Many patients with severe pain are not prescribed type of operation. Women, less well-educated people and drug abusers Pain after amputation are more likely to be under-treated. Following amputation almost all patients will experi- ence phantom sensations, and for about 70% of lower Headache limb amputees these will be painful at some time. Many amputees also experience stump pain and back Headache is the most common pain complaint.

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Reduced beta- institutional variability of duplex scanning in the detection adrenoceptor sensitivity in the elderly cheap 100mg suhagra otc impotence pump medicare. Guyatt G purchase 100 mg suhagra free shipping erectile dysfunction beat, Rennie D, Evidence-Based Medicine Working Komen Breast Cancer Foundation; August 2001. How to Read a Paper: The Basics of How to use an article about disease probability for differ- Evidence-Based Medicine, 2nd ed. Evidence-Based Medicine: How to Practice and to finding and using the best evidence in caring for patients. Are there general Nomenclature principles that may usefully apply generally to senes- cence, or is senescence simply a collection of degenera- Aging: showing the effects of time; a process of change, usually tive entropic processes that have in common only that gradual and spontaneous they occur over time? Both views are supportable; Senescence: the loss of the power of cell division and growth indeed, the latter is perhaps the more common view (and function with time, leading to death) (The New Shorter among gerontologists and is the most supportable by evo- Oxford Dictionary) 1 Gerontologists consider the term aging insufficiently lutionary theory. However, gerontology, like geriatrics, has evolved precise because any process that occurs over time, for into a discipline in part because senescence entails example, rusting or development, may be reasonably several general characteristics and because impairments referred to as aging. Furthermore, although there are associated with senescence are largely predictable within reasons to imagine that "aging" is a continuum beginning a species. For example, mortality (and other senescent with development, these two terms are usually used to changes) conform (within limits) to a precise mathemat- refer to distinct processes. Specifically, development (as in ical description, the Gompertz curve, whose parameters an embryo) refers to a generative process over time nec- 2 essary for (and primarily evident at the beginning of) life, are characteristic of each species. Similarly, dietary restriction dramatically reduces many age-related whereas senescence refers to a degenerative process ulti- impairments and increases maximum life span across a mately incompatible with (and primarily evident at the wide range of phyla. Whether development and aging form, in any These general characteristics and the specificity of informative way, a mechanistic continuum is a hypothe- senescence require explanation, and seeking these ex- sis that is far from proven. Furthermore, base searches have been greatly complicated by the recent studies have suggested that senescence may entail assignment of the term aging to the process of develop- simpler and more orderly molecular processes than ment, without a concomitant general use of the term previously assumed. Thus, for example, the some of these age-related impairments as any other wisdom (or, at any rate, experience that ought to lead to disease. This integration of geriatrics into the tradi- that occur during aging are usefully considered a mani- tional medical model is an outcome of recent progress in festation of senescence. Mobbs Theories of Aging convincingly by evolutionary biologists, that senescence did not evolve because it bestowed advantage on the species, but rather senescence is essentially an evolu- Is Senescence an Entropic Process? An Evolutionary Theories of Aging essential feature of life is the low level of internal entropy that characterizes biologic entities compared to the envi- The fact that each species is characterized by a charac- ronment. Organisms maintain that low entropy state by teristic maximum life span whose value is essentially conversion of external energy (with the result of a net independent of environment indicates that, among increase in entropy, of course, when the organism and its species, senescence is determined genetically. Mechanical constraint on maximum life span and rate of senescence objects such as automobiles or test tubes are also in a has given rise to much speculation concerning the evolu- state of low entropy, but without the capacity to reduce tion of senescence. Early speculation around the turn of internal entropy by converting external energy. Thus it is the nineteenth century was that senescence as a trait that mechanical objects accrue increased entropy over evolved, similar to most traits, because species that exhib- time "merely" as a mechanical manifestation of the ited senescence would be more likely to survive than second law and in that sense can plausibly be said to species which did not senesce. Therefore the question arises: is arguments was that species not exhibiting senescence senescence merely the accumulation of random events would accumulate ill-adapted older members of the leading to a level of entropy that is incompatible with species that would compete with potentially better- life? Ulti- adapted younger members of the species, effectively mately, death is always a manifestation of entropy, but the reducing the rate at which potentially adaptive mutations pertinent question is, what is the proximal process that could be introduced into the species, thus slowing the rate leaves the organism vulnerable to entropy? The lack of rigor of such organisms senesce in a way fundamentally different arguments has long been recognized, and, particularly since Peter Medawar’s landmark monograph in 1952,5 from mechanical objects? By the view that senescence is merely a collection of degenerative processes that there has been a consensus that senescence is not a trait happen to occur over time, the second law would seem to that has been positively selected for but rather is a trait be the only generally relevant principle operative. In particular, it has other hand, by the view that some general principles exist been assumed that the force of selection diminishes after that subserve senescence, organisms would presumably reproduction, so that traits that facilitate successful differ fundamentally from mechanical objects. This general concept has been for- mulated mathematically by Charlesworth,6 who con- example will demonstrate its pertinence. A famous form 4 cluded that even if an immortal species had ever existed, of senescence is the death of the Pacific salmon.

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Patients with a colon cancer that has been resected with curative intent should have a complete structural colon examination around the time of initial diagnosis to rule out synchronous neoplasms buy cheap suhagra 100mg erectile dysfunction drug therapy. This exam can be performed by either colonoscopy or CTC; CTC has proven especially effective in the setting of a colorectal mass that prevents passage of the colonoscope buy suhagra 100 mg free shipping erectile dysfunction treatment houston, as only air insufflation is required for evaluation (69). It offers the advantage that extracolonic structures can be assessed simultaneously. If this does not reveal synchronous lesions, sub- sequent surveillance by colonoscopy or CTC should be offered after 3 years, and then, if normal, every 5 years. Inflammatory Bowel Disease: There is extensive experience with DCBE for evaluation of inflammatory bowel disease and its complications, including CRC (70,71). Pseudopolyposis is seen when extensive ulceration of the mucosa down to the submucosa results in scattered circumscribed islands of relatively normal mucosal remnants. Postinflammatory polyps reflect a nonspecific healing of undermined mucosal and submucosal rem- nants and ulcers, and are mostly multiple. Patients with extensive long-standing ulcerative colitis or Crohn’s disease have an increased risk for the development of CRC (72). Impor- tantly, cancers that develop in patients with inflammatory bowel disease differ from more typical colorectal cancers in that they generally develop not from adenomatous polyps but rather from areas of high-grade dys- plasia (73). Dysplasia is a precancerous histologic finding, and the risk of colon cancer increases with the degree of mucosal dysplasia. Dysplasia may be found in a radiographically normal-appearing mucosa, or it may be accompanied by a slightly raised mucosal lesion, a so-called dys- plasia-associated lesion or mass and as a consequence radiographically detectable. Because differentiation of adenocarcinoma and dysplasia from inflammatory or postinflammatory polyps is sometimes difficult or impos- Chapter 5 Imaging-Based Screening for Colorectal Cancer 89 sible on double-contrast enema, endoscopy and biopsy are necessary for making a final diagnosis. There are no RCTs of surveillance colonoscopy in patients with chronic ulcerative colitis or Crohn’s colitis. A case-control study has found better survival in ulcerative colitis patients in surveillance programs (74) (moderate evidence). Patients with high-grade dysplasia or multifocal low-grade dysplasia in flat mucosa should be advised to undergo colectomy. While CTC could potentially permit evaluation of the colon, it has not been formally evaluated in this setting. Special Case: Patients with High Risk of Colorectal Cancer Summary of Evidence: Essentially, there are two broad categories of hered- itary CRC–distal or proximal–based on the predominant location of disease. Colorectal cancers involving the distal colon are more likely to have mutations in the adenomatous polyposis coli (APC), p53, and K-ras genes, and behave more aggressively (75); proximal colorectal cancers are more likely to possess microsatellite instability (genomic regions in which short DNA sequences or a single nucleotide is repeated), harbor mutations in the mismatch-repair genes, and behave less aggressively, as in HNPCC (75). Familial adenomatous polyposis (FAP) and most sporadic cases may be considered a paradigm for the first, or distal, class of colorectal cancers, whereas hereditary nonpolyposis CRC more clearly represents the second, or proximal, class (75). Familial CRC is a major public health problem by virtue of its relatively high frequency. Among these, FAP accounts for less than 1%; HNPCC, also called Lynch syndrome, accounts for approximately 5% to 8% of all CRC patients. Supporting Evidence Familial Adenomatous Polyposis Familial adenomatous polyposis is an autosomal-dominant disease caused by mutations in the adenomatous polyposis coli (APC) gene. The average age of adenoma develop- ment in FAP is 16 years, and the average age of colon cancer is 39 years. Most affected patients develop >100 colorectal adenomas, and persons with more than 100 adenomas have FAP by definition. Attenuated APC (AAPC) is a variant of FAP and is associated with a variable number of adenomas, usually 20 to 100, a tendency toward right-sided colonic ade- nomas, and an age onset of CRC that is approximately 10 years later than for FAP. The CRC mortality rate is lower in FAP patients who choose to be screened compared with those who present with symptoms (76) (moder- ate evidence). Colonoscopy should be used in those with AAPC, beginning in the late teens or early 20s, depending on the age of polyp expression in the family, while sigmoidoscopy is adequate screening for most FAP patients as numerous polyps almost invariably involve the sigmoid and rectum. People who have a genetic diagnosis of FAP, or are at risk of having FAP but genetic testing has not been performed or is not feasible, should have annual sigmoidoscopy, beginning at age 10 to 12 years, to determine if they are expressing the genetic abnormality. Hereditary Nonpolyposis Colorectal Cancer (HNPCC): Hereditary nonpoly- posis colorectal cancer, also referred to as the Lynch syndrome, is the most common form of hereditary colorectal cancer. Multiple generations are affected with CRC at an early age (mean, approximately 45 years) with a predominance of right-sided CRC (approximately 70% proximal to the splenic flexure). There is an excess of synchronous CRC (multiple colorec- tal cancers at or within 6 months after surgical resection for CRC) and metachronous CRC (CRC occurring more than 6 months after surgery).

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