By P. Sugut. Dean College. 2018.
The larger the difference between the rates in two groups order alendronate 35mg fast delivery, the smaller the sample size required to show a statistically signiﬁcant difference buy cheap alendronate 35 mg on-line. It is useful to include the 95% conﬁdence intervals when results are shown as ﬁgures because the degree of overlap between them provides an approximate signiﬁcance of the differences between groups 35 mg alendronate. The interpretation of the degree of overlap is discussed in Chapter 3 (also see Table 3. Many statistics programs do not provide conﬁdence intervals around frequency statis- tics. However, 95% conﬁdence intervals can be easily computed using an Excel spread- √ sheet. The standard error around a proportion is calculated as [p(1–p)∕n] where p is Rates and proportions 259 the proportion expressed as a decimal number and n is the number of cases in the group from which the proportion is calculated. An Excel spreadsheet in which the percentage is entered as its decimal equivalent in the ﬁrst column and the number in the group is entered in the second column can be used to calculate conﬁdence intervals as shown in Table 8. The formula for the standard error is entered into the formula bar of Excel as sqrt (p × (1 − p)/n) and the formula for the width of the conﬁdence interval is entered as 1. This width, which is the dimension of the 95% conﬁdence interval that is entered into SigmaPlot to draw bar charts with error bars, can then be both subtracted and added to the proportion to calculate the 95% conﬁdence interval values shown in the last two columns of Table 8. The calculations are undertaken in proportions (decimal numbers) but are easily con- verted back to percentages by multiplying by 100, that is, by moving the decimal point two places to the right. Using the converted values, the result could be reported as ‘the percentage of male babies born prematurely was 40. This was signiﬁcantly different than the percentage of female babies born prematurely which was 20. Because the value of ‘n’ is integral in the denominator of the calculation of conﬁdence intervals, the larger the sample size, the smaller the conﬁdence will be, indicating greater precision in the result. In general, a large sample size is required to reduce 95% conﬁdence intervals below a width of 5%. The lack of overlap between the conﬁdence intervals is an approximate indication of a statistically signiﬁcant difference between the two groups (see Table 3. Research question Question: Are the babies born in regional centres (away from the hospital or overseas) more likely to be premature than babies born in local areas? Null hypothesis: That the proportion of premature babies in the group born locally is not different to the proportion of premature babies in the groups born regionally or overseas. Variables: Place of birth (categorical, three levels and) prematurity (categorical, two levels) In this research question, there is no clear outcome or explanatory variable because both variables in the analysis are characteristics of the babies. This type of question is asked when it is important to know about the inter-relationships between variables in the data set. If prematurity has an important association with place of birth, this may need to be taken into account in multivariate analyses. The row percentages in the Crosstabulation table show that there is a difference in the frequency of prematurity between babies born at different locations. This difference in percentages fails to reach signiﬁ- cance with a Pearson’s chi-square value of 5. As mentioned previously, Pearson’s chi-square may underestimate the P value when the sample size is small. For tables such as this that are larger than 2 × 2, an Exact chi-square test should be used when an expected count is low (see Section 8. In the crosstabulation, the absolute difference in per cent of premature babies between regional and overseas centres is quite large at 55. In this case, the sample size is too small to demonstrate statistical signiﬁcance when a large differ- ence of 37. If the sample size had been larger, then the P value for the same between-group difference would be signiﬁcant. Conversely, the difference between the groups may have been due to chance and a larger sample size might show a smaller between-group difference. The row percentages illustrate the problem that arises when some cells have small numbers. When a group size is small, adding or losing a single case from a cell results in a large change in frequency statistics. Because there are some small group sizes, the footnote in the Chi-Square Tests table indicates that one cell in the table has an expected count less than ﬁve. This minimum expected cell count is printed in the footnote below the Chi-Square Tests table. If a table has less than ﬁve expected observations in more than 20% of cells, the assumptions for the chi-square test are not met. However, cells and groups with small numbers are a problem in all types of analyses because their summary statistics are often unstable and difﬁcult to interpret. When calculating a chi-square statistic, most packages will give a warning message when the number of expected cases in a cell is low. Pearson’s chi-square tests may be valid when the number of observed counts in a cell is zero as long as the expected number is greater than 5 in 80% of the cells and greater than 1 in all cells. If expected numbers are less than this, then an exact chi-square based on alternative assumptions should be used. The following table is obtained when the Monte Carlo method of computing the exact chi-square is requested. The Monte Carlo P value is based on a random sample of a probability distribution rather than a chi-square distribution which is an approximation. When the Monte Carlo option is selected, the P value will change slightly each time the test is run on the same data set because it is based on a random sample of probabilities.
Polymerase Enzyme that assembles nucleotides to produce new strand of nucleic acid proven 35 mg alendronate. Originally isolated from bacteriumThermus aquaticusin hot springs of Yellowstone National Park alendronate 35mg with mastercard. Annealing (hybridization) 50°–70°C/ Primers attach to both template strands by binding with complementary 20–90 sec alendronate 35 mg low cost. Housekeeping gene detected control) & unrelated target (house- Diﬀerentiates true neg from false keeping gene or other nucleic neg due to ampliﬁcation failure. Final probe is branched & carries signal-generating enzymes that act on chemiluminescent substrate. Cleavage-based ampliﬁcation Isothermal method that uses primary probe, invader Detection of cystic ﬁbrosis, factor (Invader technology) probe, reporter probe. Labeled probe (signal-generating probe) that anneals to diﬀerent site on target added. Hybridized typing,Mycobacteriaspeciation complexes visualized with Biotin-Streptavidin method. Liquid-phase hybridization Target nucleic acid & probe interact in aqueous solution. After cancers/diseases, classiﬁcation of ampliﬁcation, sample & control nucleic acids labeled with leukemias, tumor staging, determi- 2 diﬀerent ﬂuorescent dyes & loaded onto chip. Single-stranded fragments transferred (blotted) to solid support medium by capillary action. Sequencing ladder 4-lane gel electrophoresis pattern obtained from dideoxy chain termination sequencing. Restriction site (recognition site) Nucleotide sequence recognized by restriction endonuclease. Band furthest from origin is smallest, fastest migrating fragment & ends in the 1st nucleotide in the sequence, e. Controlling Deﬁning standards of performance, developing a reporting system, & taking corrective action when necessary. Organizational goals Administrator Runs organization within framework of policies given to him/her. Work environment Supervisor Oversees activities of others to help them accomplish speciﬁc tasks. Must be available on as-needed basis to provide on-site, telephone, or electronic consultation. Clinical consultant Consultation regarding appropriateness & interpretation of tests. Testing personnel Specimen processing, test performance, & reporting of test results. Measurement instrument Instrument to compare actual performance with desired performance. Evaluator Person trained in use of instrument, familiar with intricacies of job, time to dedicate to process. Feedback mechanism Plan for sharing results of review, taking corrective action, planning for future. Contrast error An individual is rated lower than justiﬁed because of comparison with another exceptional individual. Reverse halo eﬀect Poor performance in one area inﬂuences evaluation in other areas. Recency phenomenon Judgments are made based on recent events or unusual incidents. Lean System developed by Toyota to improve quality by improving workﬂow & eliminating waste. Focuses on equipment layout, standardization of processes, cross-training, inventory management. Turnaround times are improved by grouping automated analyzers in core lab & replacing batch processing with single-piece ﬂow. Tracer Methodology Internal audit tool to evaluate quality of patient care by following a specimen through preanalytic, analytic, & postanalytic phases of testing. Should delineate responsibilities for implementation/oversight & establish time lines. Considerations Cost, performance speciﬁcations, ease of use, turnaround time, impact on quality & cost of patient care, data management/connectivity/interface capabilities. Perform; demonstrate; explain; list; outline; label C Criteria Under what conditions? Following the directions in the Blood Bank Procedure Manual; after a lecture, demonstration, & practice session; without use of notes; within 30 min; without coaching D Degree Expected standard of performance. Psychomotor Physical skills Observe & imitate a Practice a skill Adapt existing skills to meet skill new demands or originate new procedures. Aﬀective Attitudes, feelings, Receive & respond to Assess attitudes/feelings Organize & internalize values values information about into system that guides behavior. His together a variety of elements into a meaningful serum agglutinated A1cells & B cells. Management & Test-Taking Tips Education Review 595 • Set a study schedule & stick to it. Frequent, short study • Read the question & try to think of the answer without sessions are more productive than long, irregular ones. You can increase • If possible, drive to the examination site ahead of the your odds by taking an “educated guess.
It is unlikely that some of the basic problems of medical care for the poor will be resolved during the next decade to consider personalizing the medical care buy alendronate 70mg otc. A concern has been expressed that as pre-emptive treatments become available cheap alendronate 35mg mastercard, the rich in the developing and the developed nations will consume these to avoid Universal Free E-Book Store Advantages of Personalized Medicine 651 genetically predisposing risks without having to change their lifestyle discount alendronate 35mg online. Rather than worrying about such theoretical concerns, the emphasis should be on sharing genomic information with developing countries and using it to develop cost-effec- tive population-based treatment for endemic diseases in the developing countries such as malaria and tuberculosis. Personalized medicine may eventually prove to be more economical than conventional medicine. One reason for investigating person- alized medicine further in the developing countries would be ethnic variations in drug response based on pharmacogenetics as currently available pharmacogenetic data do not comprehensively explain drug response variation within the human populations. One of the many reasons the solutions are incomplete is that they are focused on Western patient donors. The genetic causes for variable drug response are heterogeneous among the various nations of the world, and a classiﬁcation/ diagnostic kit that works very well for Caucasians may work poorly for individuals of Asian descent. To generate complete, broadly useful and sensitive drug-patient classiﬁcation kits, population studies of international representation are required. Southeast Asian populations and ethnic subgroups have been poorly represented in genomics research and product development efforts. The vast majority of phar- macogenomics research is conducted in North America and Europe primarily because of the difﬁculties in obtaining specimens from countries such as Malaysia, Indonesia and many other Southeastern Asian countries. The new company has secured access to a broad range of specimens that allow for the development of pharmacogenomics classiﬁcation products for this speciﬁc population of Southeastern Asian descent. Advantages of Personalized Medicine Advantages of personalized medicine for those involved are tabulated as follows: the biopharmaceutical industry (Table 20. Drug treatment outcome represents a complex phenotype, encoded by dozens, if not hundreds, of genes, and affected by many environmental factors; therefore, we will almost always see a gradient of response. Diet, general health, and drug-drug interactions are just some of the factors that alter a drug’s performance in a given patient. The laudable, longer term objective of personalized medicine cannot be fulﬁlled however, until one more element of diagnostic testing becomes feasible by the creation of reliable methods to predict how an individual’s unique genetic status may predis- pose him/her to the development of future illness. The development of disease predis- position risk diagnostic tests that map the probability that an individual will succumb to one or more of the complex late-onset, multigenic, non-mendelian diseases that Universal Free E-Book Store Limitations of Personalized Medicine 653 Table 20. New genome-scale screening tests may lead to a phenomenon in which multiple abnormal genomic ﬁndings are incidentally discovered, analogous to the “inciden- talomas” that are often discovered in radiological studies. The “Incidentalome” in radiology has some beneﬁts resulting from discovery of unexpected potentially life- threatening conditions that can be treated prior to clinical manifestations. However, the incidentalome resulting from molecular diagnostics threatens to undermine the promise of molecular medicine in at least three ways (Kohane et al. Physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements. Patients will be subjected to unnecessary follow-up tests, causing additional morbidity. The cost of genomic medicine will increase substantially with little beneﬁt to patients. Given the current limitations of sensitivity and speciﬁcity of many genomic tests, application of these for screening of large populations to detect conditions with low prevalence will result in large numbers of false positives. Even if genomic tests were to achieve 100 % sensitivity and a false-positive rate of zero, the risk of the inciden- talome still remains. Some pathology of disease discovered incidentally never reaches clinical signiﬁcance and may not inﬂuence decision for management. For example, a large number of prostate carcinomas accurately diagnosed after the ﬁnd- ing of an elevated prostate-speciﬁc antigen level in all likelihood would not contrib- ute to an individual’s death and may not be treated. The physicians need to be educated to ensure that there is appropriate clinical justi- ﬁcation to perform and interpret these tests in a manner that ushers in the era of personalized medicine and does not allow the incidentalome to block its arrival. Information management to enable personal- ized medicine: stakeholder roles in building clinical decision support. Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2. What it will take to achieve the as-yet-unfulﬁlled promises of health information technology. Assessing and reporting hetero- geneity in treatment effects in clinical trials: a proposal. The Lausanne Institutional Biobank: a new resource to catalyse research in personalised medicine and pharmaceutical sciences. Using evidence to combat overdiagnosis and overtreatment: evaluating treatments, tests, and disease deﬁnitions in the time of too much. Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and com- panion diagnostics. Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer. Small-molecule modulators of p53 family signaling and antitu- mor effects in p53-deﬁcient human colon tumor xenografts. Development of predictive genetic tests for improving the safety of new medicines: the utilization of routinely collected electronic health records. Universal Free E-Book Store Chapter 21 Ethical Aspects of Personalized Medicine Introduction to Ethical Issues Most of the ethical aspects of personalized medicine are based on pharmacogenetics, genetic screening and impact on healthcare. Understanding the social effects of genomics requires an analysis of the ways in which genetic information and a genetic approach to disease affect people individually, within their families and communities, and in their social and working lives. This information will lead to measures for the prevention of stigmatization and discrimination of different popu- lations on ethnic grounds. Ethical Issues of Pharmacogenetics Some of the ethical questions raised by pharmacogenetics include the following: • The issue of ensuring equality in medical care, when genetics can predict which patients are less likely to beneﬁt from the available pharmacotherapy. The Nufﬁeld Council on Bioethics in a report published in 2003 has reviewed this topic ( www.
The decision on extraction is dependent on the age of the child alendronate 35mg on line, the stage of development of the dentition order alendronate 70 mg, and the occlusion order 35 mg alendronate with visa. Whereas there may be different treatment options with regard to carious first permanent molars, the clinician should usually attempt to retain incisors and/or canines, with extensive caries whenever possible. It may take up to 5 years after eruption for the root to complete its formation and develop an apical constriction. Key Point Whenever it is thought that caries removal might result in a pulpal exposure, efforts should be made to preserve pulp vitality in order to enable normal root maturation to occur. Indirect pulp capping If it is thought that exposure is likely to occur with full caries removal then sometimes it is expedient to leave caries in the deepest part of the lesion. Place a radio-opaque, biocompatible base over the remaining carious dentine to stimulate healing and repair. It is important to completely remove caries from all the lateral walls of the cavity before placement of a restoration since failure to do so will result in spread of secondary caries and the need for future intervention. Alternatives suggested include adhesive resins, and glass ionomer cements, but as yet there are no published studies looking at these techniques in permanent teeth. Whichever material is utilized, the crucial factor is to isolate the pulp well from the oral environment. Re-investigation of these teeth after about 6 months when the pulp has had an opportunity to lay down reparative dentine used to be recommended. However studies have found that the residual carious dentine mostly re-mineralizes and hardens and caries progression does not occur in the absence of micro-leakage. Returning to the operative site, to complete caries removal increases the risk of pulp exposure, therefore the authors consider it wiser to perform the indirect pulp capping and definitive restoration in one appointment. The direct pulp cap When a small exposure is encountered during cavity preparation the operator can place a direct pulp cap. Total etching and sealing with a dentine-bonding agent has been tried but this resulted in increased non-vitality, so it is now contraindicated. As in traumatic exposures, pulp capping has given disappointing results compared with the technique of partial pulpotomy, so should only be used if a pulpotomy cannot be performed. For all techniques in which the pulp is preserved it is important to assess the situation correctly before embarking on the treatment: • There should be no history of spontaneous pain. Pulpotomy Pulpotomies are successful in young teeth due to their increased pulpal circulation and ability to repair. The procedure consists of applying rubber dam after local analgesia and then clearing all lateral margins around the exposure and the pulpal floor of any caries. The superficial layer of the exposed pulp and the surrounding dentine are excised to a depth of 2 mm using a high speed diamond bur. The technique is the same as the Cvek pulpotomy described in Chapter 12473H for pulp exposure in traumatized teeth. Whether sufficient tissue has been removed is ascertained by gently irrigating the remaining pulp surface with isotonic saline until bleeding stops. If bleeding does not cease easily, it is probable that the tissue is still inflamed and a further millimetre of pulp tissue is removed. Similarly if there is no bleeding at all then further pulp tissue should be removed until bleeding is found. After haemostasis has been obtained a soluble paste of calcium hydroxide is applied to the wound surface. It is important that there is no blood clot between the wound surface and the dressing as this will prevent repair and reduce the chances of success. Hence at present calcium hydroxide, the tried and tested remedy should still be used. In order to aid repair, the clinician should apply dry sterile pellets of cotton wool carefully with modest pressure to adapt the calcium hydroxide medicament to the prepared cavity and remove excess water from the paste. As in pulp capping it is essential that the operator fills the cavity with a material that provides a good hermetic seal. The latter can be the final restoration as there is no need to re-enter the wound site. Although the presence of a dentinal bridge radiographically represents a success, its absence does not indicate failure. After a year, success is represented by a tooth where there are no signs of clinical or radiographic pathology and where the root has developed apically and thickened laterally. It is therefore considered the treatment of choice when there has been a pulp exposure in an immature permanent tooth. In a recent study only 36% of young root filled molar teeth were considered a success. Hence, pulpectomy should be reserved only for cases exhibiting symptoms where the pulp is irreversibly damaged. It is important to stress that the haemorrhage must cease before placing the lining. There is no need to re-investigate the site, so consider the restoration as definitive. This term covers a range of developmental anomalies from small white, yellow, or brown patches to extensive loss of tissue from almost the whole enamel surface. It is characterized by a very rapid breakdown of the enamel, which can be extremely sensitive. The difficulties of cleaning a partially erupted tooth are then compounded by the sensitivity. This produces an area where plaque builds up and which leads to rapid carious attack.