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Staging of lung cancer: tumor discount acivir pills 200mg fast delivery common acute hiv infection symptoms, node buy acivir pills 200 mg on line antiviral research abbreviation, metastasis (TNM) descriptors Site Name Comment Primary lesion T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor <3cm or less surrounded by lung or visceral pleura without invasion proximal to lobar bronchus T2 Tumors >3cm; any tumor invading main bronchi but >2cm from the carina; invasion of visceral pleura; obstructive pneumonitis extending to hila but does not involve entire lung T3 Tumor of any size that directly invades chest wall, diaphragm, mediastinal pleura, or parietal pericardium; or involves main bronchus within 2cm of carina, but does not involve carina; or results in obstructive atelectasis or pneumonitis of entire lung T4 Tumor invades any of the following: mediastinum, heart great vessels, trachea, esophagus, vertebral body or carina; malignant ipsilateral pleural or peri cardial effusion; satellite tumor nodule within primary tumor lobe Lymph nodes N0 No regional lymph node metastases N1 Spread to ipsilateral peribronchial or hilar nodes N2 Spread to ipsilateral mediastinal or subcarinal nodes N3 Spread to contralateral mediastinal or hilar nodes; scalene nodes; supraclavicular nodes Distant disease M0 No distant metastases M1 Distant metastases present Data from Mountain15 and Mountain. Histologic subtypes including squamous cell, adenocarcinoma, and large cell carcinoma are categorized as non–small-cell lung cancer (NSCLC) due to the similar treatment and prognosis based on stage. Supporting Evidence: Staging of lung cancer is critical for choosing the appropriate treatment and for assessing overall prognosis. Staging is cate- gorized by the tumor, node, metastasis (TNM) system as set forth by the American Joint Committee on Cancer and takes into account features of the primary tumor as well as dissemination to the mediastinum and distant organs (Tables 4. Computed tomography is the preferred modality for initially establishing the diagnosis of lung cancer and providing initial staging information, as it is widely available, more sensitive than chest radiograph, rapid to perform, and guides further workup. The use of intravenous contrast is largely based on physician preference, as few studies have been performed to assess interpretive difference. Those that have been performed do not show clear superiority of enhanced over unenhanced scans (72–74). Stage of non–small-cell lung cancer (NSCLC) based on TNM classification 0 Carcinoma in situ 1A T1N0M0 1B T2N0M0 2A T1N1M0 2B T2N1M0 T3N0M0 3A T3N1M0 T1–3N2M0 3B Any T4 Any T3 4 Any M1 Data from Mountain15 and Mountain. Difficulty may arise in the evaluation of invasion into the chest wall and mediastinum. Rib erosion, bone destruction, or tumor adjacent to mediastinal structures pro- vides reliable evidence of invasion. Without these features, proximity and secondary signs (greater than 3cm of contact with the pleural surface, pleural thickening, absent fat planes, and obtuse angle of tumor with the chest wall) are only moderately helpful in predicting invasion (75–78), and localized chest pain is a more specific finding (75). Magnetic resonance imaging is slightly more successful at detecting chest wall invasion (79–81) owing to better spatial resolution particularly in the lung apex (Table 4. Using dynamic cine evaluation of the tumor during breathing provides reliable exclusion of parietal pleura invasion, although false-positive results still occur (82–84). Because size is the determining factor for the interpretation of mediastinal adenopathy, usually 1cm in short axis, CT is an imperfect tool for catego- rization of mediastinal disease. Twenty studies performed between 1991 and 2001 showed sensitivity ranges from 26% to 86% and specificity from 57% to 93% (85–104). Pooling the 3438 patients among these studies (preva- lence of adenopathy 28%) gives a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 57%, 82%, 56%, and 83%, respectively, for mediastinal disease (17). Despite advances in CT technology, there does not appear to be a significant improvement in the ability to stage the mediastinum. Few studies continue to look at CT as a staging tool, and those that do are generally studies devoted to PET imaging; thus CT technique and interpretive information is relatively spotty. The range of sensitivity (43–83%), specificity (52–94%), and accu- racy (63–86%) all overlap with previous studies (105–108). Suggested imaging studies for staging lung cancer Non–small-cell lung cancer Small-cell lung cancer CT of chest CT of chest/abdomen Whole-body PET MRI brain Bone scintigraphy (optional; see text) Bone scintigraphy MRI brain (optional; see text) PET, positron emission tomography. Chapter 4 Imaging of Lung Cancer 69 While MRI staging is feasible, it is not widely utilized due to cost and availability. It has been suggested that MR is better at detecting hilar lymph nodes, although the clinical utility of this is unclear (109,110). The few studies performed suggest that unenhanced MRI is at best equivalent to CT (111,112), although gadolinium or new iron oxide contrast agents may ultimately increase the utility of MRI (111–113). Fluorodeoxyglucose (FDG)-PET was initially hoped to provide defini- tive noninvasive staging of the mediastinum. Rather than using size as a criterion, metabolism of glucose is used as a marker of malignancy. Early studies fostered extreme optimism and it was not uncommon to see sen- sitivity or specificity quoted at 100% (97,114–118). In studies without either perfect sensitivity or specificity, sensitivity ranged from 52% to 93% and specificity 43% to 93% (87–89,92,94,95,119–124). Pooling the aforemen- tioned studies resulted in sensitivity, specificity, PPV, and NPV of 84%, 89%, 79%, and 93%, respectively, in 1045 patients with a prevalence of mediastinal disease of 32% (17). A similar sensitivity and specificity (85% and 90%) were found in a second meta-analysis (125). In the setting of a positive CT scan, sensitivity approached 100%, whereas specificity fell to 78%. When the CT did not reveal adenopathy, PET was 82% sensitive and 93% specific (125). Most recently, five studies, each with over 100 patients, have presented a less optimistic view of PET for staging the medi- astinum, with sensitivity ranging from 61% to 94% and specificity from 77% to 84% (105,126–129).

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Yet when the yet one recent population-based study found that almost studies were done buy acivir pills 200mg online symptoms of primary hiv infection video, it was found that suppressing VPBs 50% of new-onset CHF occurred in people age 80 or with certain agents increases patient mortality and older and that approximately 50% of these had systolic increasing bone mineral density with fluoride increases CHF purchase 200 mg acivir pills with amex hiv infection uk 2012. How should the cating a benefit, the relative risk reduction (RRR), may 40% to 50% of patients over 70 whose CHF is diastolic be quite large when the absolute risk reduction (ARR), 16 (an ejection fraction ≥45%) be treated? In EBM, a term often used to define the size of the treatment benefit is the Treatment Studies: Applying Results number needed to treat (NNT), which is the number of people who would need to be treated with the active to Older Adults intervention, rather than the control, over a specific time period to prevent one additional patient from having Figure 1. Several of these are key principles in geriatric the primary outcome of the Systolic Hypertension in the medicine and overlap the specific biologic, social and eco- Elderly Program trial, is shown to occur in approximately nomic, and epidemiologic issues discussed in the User’s 8% of control patients and 5% of treated patients. In other words, treating 33 patients with patient, and treatment differences that can influence the isolated systolic hypertension (ISH) over 4. Similar terms describe the results of diagnostic tests, including the likelihood ratio, Patient–Disease Interactions which compares the probability that people with an abnormal test actually have the disease in question to the Despite the concerns about reduced therapeutic efficacy probability that they have an abnormal test result but not that follow, it is important to recognize that older adults the disease. Criteria Therapy/prevention Differential diagnosis Diagnostic tests Harm/etiology Prognosis Primary • Was the assignment of • Did the study • Was there an • Were there clearly • Was there a validity patients to treatments patients represent independent, blind identified comparison representative requirements randomized? Secondary • Were patients, health • Was the diagnostic • Did the results of • Is the temporal • Were objective Validity workers, and study workup the test being relationship correct? Results • How large was the • What were the • Are likelihood • How strong is the • How large is the treatment effect? Applicability • Can the results be • Are the study • Will the • Are the study results • Were the study applied to my patient patients similar to reproducibility of applicable to my patients similar to care? Glossary of evidence-based vocabulary included in the fourth edition of Geriatric Medicine. Terms relevant to study design Case-control study Case-control studies examine outcomes that are rare or take a long time to develop. Cases are identified in which the outcome occurred; controls are then selected with similar age, sex, and medical conditions excepting the target outcome. Investigators assess the relative frequency of exposure to the alleged harmful agent, controlling for differences in the variables. Case series Descriptions of a series of patients; case series lack a control group. Cohort study Involves identification of two or more groups (cohorts) of patients, one which did receive the exposure of interest, and one which did not, and following these cohorts forward for the outcome of interest. Double-blind (DB) A trial in which neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage. Heterogeneity In a meta-analysis, results of individual studies suggest that they were performed in different populations. Can compromise the validity of a meta-analysis; significant heterogeneity indicates decreased likelihood that chance alone is responsible for any observed differences in treatment effects between studies. Internal validity How well results fit the population in which the model was generated. Meta-analysis Quantitative review of systematically chosen literature, the hallmark of which is statistical synthesis of the numerical outcomes of several trials that all asked the same question. Multicenter A clinical trial conducted at more than one site, but following the same protocol at all locations. Placebo-controlled (PC) A trial in which the effectiveness of the drug is compared to that of a placebo. Prospective cohort study An observational study that follows a large group (a cohort) of people forward in time Randomized controlled trial (RCT) Experiment in which individual are randomly allocated to receive or not receive an experimental preventative, therapeutic, or diagnostic procedure and then followed to determine the effect of the intervention. Systematic review Explicit, structured presentation of results of an unbiased literature review, using predetermined search and appraisal definitions. Terms relevant to study results Absolute risk reduction (ARR) The difference between the control event rate (CER) and the experimental treatment event rate (EER). ARR = CER - EER 95% confidence interval (CI) An estimate of the precision of a measurement by determining, with 95% accuracy, that the measurement includes the "true" value for the population. The broader the CI range, the more uncertain is the true value of the measurement; CIs that cross zero do not reach clinical significance. Experimental event rate (EER) Rate of the outcome in the experimental treatment group. Intention-to-treat (ITT) Results that include every individual originally randomized, regardless of whether or not they completed the trial. Likelihood ratio (LR) Positive LR = probability of an abnormal diagnostic or screening test result (including clinical signs or symptoms) in patients with the disorder of interest compared to the probability of the abnormal result in patients without the disorder (Sn/1 - Sp).

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H ence buy cheap acivir pills 200mg on-line anti viral load, when reading a paper about a RCT cheap acivir pills 200mg without prescription new hiv infection symptoms, you should look for a sentence which reads som ething like this (which is taken from M ajeed and colleagues’ cholecystectom y paper described above): "For a 90% chance of detecting a difference of one night’s stay in hospital using the M ann-W hitney U -test [see Chapter 5, Table 1], 100 patients were needed in each group (assum ing SD of 2 nights). This 70 ASSESSIN G M ETH OD OLOG ICAL QU ALITY gives a power greater than 90% for detecting a difference in operating tim es of 15 m inutes, assum ing a SD of 20 m inutes. U nderpowered studies are ubiquitous in the m edical literature, usually because the authors found it harder than they anticipated to recruit their subjects. If the authors were looking at the effect of a new painkiller on the degree of postoperative pain, their study m ay only have needed a follow up period of 48 hours. On the other hand, if they were looking at the effect of nutritional supplem entation in the preschool years on final adult height, follow up should have been m easured in decades. Even if the intervention has dem onstrated a significant difference between the groups after, say, six m onths, that difference m ay not be sustained. As m any dieters know from bitter experience, strategies to reduce obesity often show dram atic results after two or three weeks but if follow up is continued for a year or m ore, the unfortunate subjects have (m ore often than not) put m ost of the weight back on. Completeness of follow up It has been shown repeatedly that subjects who withdraw from ("drop out of") research studies are less likely to have taken their tablets as directed, m ore likely to have m issed their interim check ups, and m ore likely to have experienced side effects on any m edication than those who do not withdraw. People on a weight reducing program m e are m ore likely to continue com ing back if they are actually losing weight. N ote that you should never look at the "adverse reaction" rate in the intervention group without com paring it with that on placebo. Clearly, patients who die will not attend for their outpatient appointm ents, so unless specifically accounted for they m ight be m isclassified as "dropouts". This is one reason why studies with a low follow up rate (say below 70% ) are generally considered invalid. Sim ply ignoring everyone who has withdrawn from a clinical trial will bias the results, usually in favour of the intervention. It is therefore standard practice to analyse the results of com parative studies on an intent to treat basis. Conversely, withdrawals from the placebo arm of the study should be analysed with those who faithfully took their placebo. If you look hard enough in a paper, you will usually find the sentence "Results were analysed on an intent to treat basis", 72 ASSESSIN G M ETH OD OLOG ICAL QU ALITY but you should not be reassured until you have checked and confirm ed the figures yourself. There are, in fact, a few situations when intent to treat analysis is, rightly, not used. The m ost com m on is the efficacy analysis, which is to explain the effects of the intervention itself and is therefore of the treatm ent actually received. But even if the subjects in an efficacy analysis are part of a RCT, for the purposes of the analysis they effectively constitute a cohort study (see section 3. You should also, at this stage, identify what statistical tests, if any, were used to analyse the results (see Chapter 5). If you are clear about these things before reading the rest of the paper, you will find the results easier to understand, interpret and, if appropriate, reject. You should be able to com e up with descriptions such as: This paper describes an unblinded random ised trial, concerned with therapy, in 267 hospital outpatients aged between 58 and 93 years, in which four layer com pression bandaging was com pared with standard single layer dressings in the m anagem ent of uncom plicated venous leg ulcers. Percentage healing of the ulcer was m easured from baseline in term s of the surface area of a tracing of the wound taken by the district nurse and calculated by a com puter scanning device. This is a questionnaire survey of 963 general practitioners random ly selected from throughout the U K, in which they were asked their year of graduation from m edical school and the level at which they would begin treatm ent for essential hypertension. Response options on the structured questionnaire were ‘90–99 m m H g’, ‘100-109 m m H g’, and ‘110 m m H g or greater’. Results were analysed using a Chi squared test on a 3 x 2 table to see whether the threshold for treating hypertension was related to whether the doctor graduated from m edical school before or after 1975. W hen you have had a little practice in looking at the m ethods section of research papers along the lines suggested in this chapter, you will find that it is only a short step to start using the checklists in Appendix 1 or the m ore com prehensive "U sers’ guides to the m edical literature" referenced in Chapter 3. I will return to m any of the issues discussed here in Chapter 6, in relation to evaluating papers on drug trials.

The program may feature a speaker who addresses a topic of importance to the members and then opens the topic to discussion and questions order 200 mg acivir pills overnight delivery hiv infection rates caribbean. Or it may be a videotaped presentation purchase acivir pills 200 mg with visa anti virus warning, followed by a discussion of the taped 158 support groups 159 subject. Or the program may be the posing of several questions by the chairman, each question followed by a general discussion. Partway through the program, the group takes a break to move about and enjoy a cup of coffee, and after the program, there may be more socializing. The group is made up of people with Par- kinson’s and their spouses or other caregivers. A few visitors may also be present: perhaps another family member or a friend of one of the "regulars," or a new person with Parkinson’s or a spouse who is coming to see what we have to offer. If a focused discussion is planned (rather than a speaker or a videotaped pres- entation), the group may remain as one group, or it may split up into two groups so that spouses and other caregivers can discuss their concerns separately from the people with Parkinson’s. If a prominent speaker or a panel is scheduled for the program, mem- bers of other Maine support groups may have joined us for the meeting. It is a group ranging in size from a dozen people to more than a hundred, who generally meet once a month to learn about the care and the treatment of Parkinson’s, exchange insights and newly learned coping techniques, and offer friendship, support, and understanding to one another. Some groups follow a format similar to ours; oth- ers include ballroom dancing in their social time; some break for an exercise period; some serve baked goods, other snacks, and soft drinks, in addition to coffee. Some groups organize theater trips and outings in addition to their regular meetings. Some groups split up for general discussion: people with Parkinson’s in one group and caregivers in another. Some include anyone with Par- kinson’s, while others limit their membership to either older patients or younger patients and their families. Blaine and I cochair the meetings; we arrange for a speaker, a videotape, or a discussion. A secretary publicizes the meetings and keeps a very brief record of each meeting and a list of the names and addresses of new visi- tors. When members of the community pass away, mourners sometimes send donations to our group in lieu of flowers to the family. We also bought a television and a VCR for the church where we meet, with the understanding that we can use them at our meetings. Our support group has given us the opportunity to learn a great deal about Parkinson’s disease and what we can do for our- selves in treating it. Our speakers have included doctors, psychol- ogists, physical therapists, occupational therapists, a hearing specialist, and a nutritionist, all speaking on various aspects of the management of Parkinson’s disease. A speaker from Sandoz (a pharmaceutical company) talked to us and answered our questions about Parlodel (bromocriptine), one of its products. A representa- tive from the Eastern Agency on Aging informed us about com- munity services (such as adult day care) that are available to local senior citizens. A program we later held was a presentation of the care of the patient’s teeth, gums, and mouth, to address the diffi- culty that people with Parkinson’s have (because of dry mouth) in maintaining good oral hygiene. The speakers say that they learn a great deal from us during the discussion period when we contribute our ideas and voice our concerns. The videotapes we rent from Parkinson’s organizations have been instructive to our group. They have featured exercise pro- grams for people with Parkinson’s, roundtable discussions on Par- kinson’s, and doctors lecturing on Parkinson’s. What we learn from one another is as valuable as what we learn from speakers and tapes. What I value most of all is hearing others express the same things I have experienced but have not been able to communicate to people who don’t have Parkinson’s. No one else understands us as well as other people with Parkinson’s, not even our spouses or closest family members. Of course, the spouses and other caregivers feel the same way about sharing their feelings and insights. At the support group, even in the midst of our frustrations, we find joy and laughter, hope and determination. In addition to our regular meetings, our members look for- ward to two special occasions together: the annual picnic in July and the restaurant outing during the Christmas season.

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