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1.  Management of Superficial to Partial-Thickness Wounds 
Journal of Athletic Training  2007;42(3):422-424.
Reference/Citation: Wiechula R. The use of moist wound-healing dressings in the management of split-thickness skin graft donor sites: a systematic review. Int J Nurs Pract. 2003; 9:S9–S17.
Clinical Question: Do rates of healing, infection, and pain differ depending on whether nonmoist or moist dressings are used to manage superficial to partial-thickness wounds?
Data Sources: Investigations were identified by CINAHL, MEDLINE, Pre-MEDLINE, Cochrane Library, Current Contents, Health STAR, EMBASE, Expanded Academic Index, and Dissertation Abstracts International searches. The search terms included skin, graft, and donor. Additional searches were performed with reference lists and bibliographies of retrieved studies.
Study Selection: To be included in the review, each study had to fulfill the following criteria: it had to be an intraindividual or prospective randomized controlled trial of human subjects; it had to include patients with postharvest split-thickness skin graft donor sites; it had to evaluate the effectiveness of primary and secondary wound dressings; and it had to have outcome measures that included healing (objective), infection (subjective), and pain (objective).
Data Extraction: Data extraction and study quality assessment procedures were developed specifically for this review based on Cochrane Collaboration, Centre for Reviews and Dissemination, and Joanna Briggs Institute protocols and were performed independently by the author. Details of the procedures were not fully explained. The principal outcome measures were healing (proportion of sites healed within the study period or time to complete healing), rate of infection, and pain scores. The studies were grouped according to broad dressing type (nonmoist and moist) and specific types of moist dressings (hydrocolloids and polyurethane semipermeable transparent films). When comparable, study results were pooled and analyzed with a fixed-effects model. Data within broader dressing categories (nonmoist and moist) were analyzed with a random-effects model. χ 2 analysis was used to determine heterogeneity among the studies. RevMan software (version 4.04; Cochrane Centre, Oxford, UK) was used for statistical analysis.
Main Results: The searches identified 111 studies and 1 integrative review, of which 58 studies met the inclusion and exclusion criteria. Inconsistency and variation in outcome measures and incomplete reporting of results prevented analysis of many studies. Wound healing was measured by days to complete healing (when dressings could be removed without trauma and pain) and wounds healed by day X (removal of dressings at regular intervals). Wound infection was subjectively measured based on clinical signs of infection (edema, heat, pain, or smell). Visual analog scales were used to measure pain levels.
Among the broad categories of nonmoist (sterile gauze, fine mesh gauze, Xerofoam [Tyco Healthcare Group LP, Mansfield, MA]) and moist (DuoDERM hydrocolloid [ConvaTec, Princeton, NJ], Tegaderm transparent film [3M Health Care, St Paul, MN], Opsite transparent film [Smith & Nephew, London, UK]) dressings, the outcomes of healing, infection, and pain were analyzed. In 6 studies, the findings significantly favored moist dressings, compared with nonmoist dressings, for days to complete healing (weighted mean difference [WMD] = −3.97, 95% confidence interval [CI] = −5.91, −2.02). In 9 studies, wounds healed by day X (day 7, 8, 9, 10, or 12) were analyzed. The results were varied and inconclusive because of a small number of trials and subjects. Among 10 studies, no significant difference was noted in infection rates between nonmoist and moist dressings (odds ratio [OR] = 0.41, 95% CI = 0.14, 1.18). Three studies using visual analog scales for the outcome of pain were converted into a uniform scale of 1 to 10 (10 representing most painful). The findings significantly favored moist dressings over nonmoist dressings (WMD = −1.75, 95% CI = −2.94, −0.56).
Among nonmoist and specific types of moist dressings, a subset analysis was performed to examine the outcomes of healing, infection, and pain. For days to complete healing, 2 investigations significantly favored hydrocolloid dressings over nonmoist dressings (WMD = −2.19, 95% CI = −2.89, −1.49). Additionally, in 2 studies, hydrocolloid dressings were significantly favored over other moist dressings (semiocclusive hydrocolloid and transparent film) for days to complete healing (WMD = −1.45, 95% CI = −2.17, −0.74). In 3 studies, the data significantly favored polyurethane semipermeable transparent film dressings over nonmoist dressings for days to complete healing (WMD = −2.82, 95% CI = −3.58, −2.07). For infection rates, 4 studies significantly favored hydrocolloid dressings over nonmoist dressings (OR = 0.21, 95% CI = 0.07, 0.65). In 4 other studies, polyurethane semipermeable transparent film dressings were significantly favored over nonmoist dressings with regard to infection rates (OR = 0.28, 95% CI = 0.09, 0.91). For the outcome of pain, varied outcome measures and insufficient data prevented analysis among specific types of moist dressings.
Conclusions: Moist dressings decreased the days to complete healing and pain scores when compared with nonmoist dressings. Among the broad categories of nonmoist and moist dressings, no differences were found in infection rates. The data on specific types of moist dressings revealed that days to complete healing were decreased with hydrocolloid dressings compared with nonmoist and other moist dressings. Hydrocolloid dressings also decreased infection rates compared with nonmoist dressings. Polyurethane semipermeable transparent film dressings also decreased days to complete healing and infection rates compared with nonmoist dressings. Overall, the data indicated that hydrocolloid dressings are more effective than nonmoist dressings in terms of rates of healing, infection, and pain in the management of superficial to partial-thickness wounds. The variations in outcome measures among the included studies should be considered in interpreting these findings.
PMCID: PMC1978464  PMID: 18059999
moist dressings; abrasions
2.  Topical Silver for Infected Wounds 
Journal of Athletic Training  2009;44(5):531-533.
Abstract
Reference/Citation:
Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007(1);CD005486.
Clinical Question:
What is the clinical evidence base for silver dressings in the management of contaminated and infected acute and chronic wounds?
Data Sources:
Investigations were identified by Cochrane Wounds Group Specialized Register (2006), CENTRAL (2006), MEDLINE (2002–2006), EMBASE (2002–2006), CINAHL (2002–2006), and digital dissertations (2006) searches. Product manufacturers were contacted to identify additional eligible studies. The search terms included wound infection, surgical wound infection, ulcer, wound healing, and silver.
Study Selection:
Each study fulfilled the following criteria: (1) The study was a randomized controlled trial of human participants that compared dressings containing silver with any dressings without silver, dressings with other antiseptics, or dressings with different dosages of silver. (2) The participants were aged 18 years and older with contaminated and infected open wounds of any cause. (3) The study had to evaluate the effectiveness of the dressings using an objective measure of healing. No language or publication status restrictions were imposed, and participants could be recruited in any care setting. Studies were excluded if the wounds were ostomies (surgically formed passages).
Data Extraction:
Study quality assessment was conducted independently by 3 authors using the Dutch Institute for Health Care Improvement and Dutch Cochrane Centre protocols. Characteristics of the study, participants, interventions, and outcome measures were extracted by one author and verified by a second using a standard form. The principal outcome measure was healing (time to complete healing, rate of change in wound area and volume, number and proportion of wounds healed within trial period). Secondary measures were adverse events (eg, pain, maceration, erythema), dressing leakage, and wound odor. Based on the unique comparisons in the studies, a meta-analysis was not conducted. As a result, summary estimates of treatment effect were calculated for each outcome comparison. RevMan software (version 4.2; Cochrane Centre, Oxford, United Kingdom) was used for statistical analysis.
Main Results:
Specific search criteria identified 31 studies for review, of which 3 met the inclusion and exclusion criteria. Lack of randomization and absence of wound infections excluded the majority of studies from the review. In the 3 studies selected, silver-containing dressings were compared with nonsilver dressings and dressings with other antimicrobials. One group used a silver-containing foam dressing and a nonsilver foam dressing; another group used a silver-containing alginate and a nonsilver alginate; and a third group used a silver-containing foam and various dressings (nonsilver foams, alginates, hydrocolloids, and gauze and other antimicrobial dressings). Sample sizes ranged between 99 and 619 participants. Most of the wounds in the included studies were pressure, diabetic, and venous leg ulcers. Wound infection was subjectively defined by 1 group as the presence of 2 or more signs and symptoms (eg, continuous pain, erythema, heat, or moderate to high levels of exudate) and by the other 2 groups as signs of critical colonization (eg, delayed healing, increased pain and exudate levels, discoloration, and odor). The primary measure in the included studies was healing outcome. The 3 groups used various assessments of healing, including relative and absolute reduction in wound area and number of wounds healed during the trial period. The trial period in each study was 4 weeks. In the 3 trials, the authors randomized the participants to the treatment groups.
Examining healing, one group (129 participants) compared Contreet silver foam (Coloplast A/S, Humlebaek, Denmark) with Allevyn foam (Smith & Nephew, St-Laurent, Quebec, Canada). The authors reported no differences for rates of complete healing (risk difference [RD]  =  0.00, 95% confidence interval [CI]  =  −0.09, 0.09) and median wound area reduction (weighted mean difference [WMD]  =  −0.30 cm2, 95% CI  =  −2.92, 2.35). However, Contreet was favored over Allevyn (P  =  .034) for median relative reduction in wound area (WMD  =  −15.70 cm2, 95% CI  =  −29.5, −1.90). One group (99 participants) compared Silvercel silver alginate (Johnson & Johnson Wound Management, Somerville, NJ) with Algosteril alginate (Johnson & Johnson Wound Management). The authors found no differences in rates of complete healing (RD  =  0.00, 95% CI  =  −0.06, 0.05), mean absolute (WMD  =  4.50 cm2, 95% CI  =  −0.93, 9.93) and relative wound area reduction (WMD  =  −0.30 cm2, 95% CI  =  −17.08, 16.48), or healing rate per day (week 1 to 4) (WMD  =  0.16 cm2, 95% CI  =  −0.03, 0.35). One group (619 participants) compared Contreet with various dressings (nonsilver foams, alginates, hydrocolloids, and gauze and other antimicrobial dressings). For median relative wound area reduction, the authors noted a superiority of Contreet over the various dressings (P  =  .0019).
Examining secondary outcomes, 2 groups used subjective analysis to compare adverse reactions among the dressings. One group reported no difference between Contreet (in satellite ulcers, deterioration of periwound tissue) and Allevyn (in satellite ulcers, maceration, eczema) (RD  =  0.02, 95% CI  =  −0.07, 0.12), and one group found no difference between Silvercel (in pain during dressing change, eczema, periwound erythema, maceration) and Algosteril (in pain during dressing change, eczema, erythema) (RD  =  −0.01, 95% CI  =  −0.12, 0.11). Two groups subjectively assessed leakage among silver and nonsilver dressings. The data from one group demonstrated superiority of Contreet over Allevyn (P  =  .002; RD  =  −0.30, 95% CI  =  −0.47, −0.13), and one group found Contreet better than various dressings (eg, nonsilver foams, alginates, hydrocolloids, and gauze, and other antimicrobial dressings) (P  =  .0005; RD  =  −0.11, 95% CI  =  −0.18, −0.05). Using a subjective 4-point scale, one group compared silver and nonsilver dressings and reported a difference favoring Contreet over Allevyn in terms of wound odor (P  =  .030; RD  =  −0.19, 95% CI  =  −0.36, −0.03).
Conclusions:
Overall, this review provides no clear evidence to support the use of silver-containing foam and alginate dressings in the management of infected chronic wounds for up to 4 weeks. However, the use of silver foam dressings resulted in a greater reduction in wound size and more effective control of leakage and odor than did use of nonsilver dressings. Randomized controlled trials using standardized outcome measures and longer follow-up periods are needed to determine the most appropriate dressing for contaminated and infected acute and chronic wounds.
doi:10.4085/1062-6050-44.5.531
PMCID: PMC2742464  PMID: 19771293
antiseptics; moist dressings; critical colonization; contamination
3.  Islamic bioethics: a general scheme 
No doubt life in its all forms enjoys a very high status in Islam. Human life is one of the most sacred creatures of God. Therefore, it must be appreciated, respected and protected. In this regard, the paper refers to different parts. The first part studies the value of life in Islam. It helps to understand why life must be appreciated and respected. The second part sheds some light on the nature of the Islamic bioethics. Discussing the sources and authorities in the Islamic bioethics, in this part we will study the way of life protection which is regulated by the Islamic law and bioethics. Part three reflects on some important issues in bioethics from an Islamic perspective. Concerning the Islamic believes, physical health maintenance and disease treatment are two important aspects of the Islamic teachings. In respect to the beginning of human life; firstly, we will see that reproduction must occur in the context of a legitimate and stable family. Secondly, we will study family planning and abortion. With respect to the end of life, issues such as suicide and euthanasia will be studied. Finally organ transplantation will be discussed.
PMCID: PMC3713653  PMID: 23908711
Life; Abortion; Euthanasia; Brain death; Organ transplantation
4.  Demystified … Tissue microarray technology 
Molecular Pathology  2003;56(4):198-204.
Several “high throughput methods” have been introduced into research and routine laboratories during the past decade. Providing a new approach to the analysis of genomic alterations and RNA or protein expression patterns, these new techniques generate a plethora of new data in a relatively short time, and promise to deliver clues to the diagnosis and treatment of human cancer. Along with these revolutionary developments, new tools for the interpretation of these large sets of data became necessary and are now widely available. Tissue microarray (TMA) technology is one of these new tools. It is based on the idea of applying miniaturisation and a high throughput approach to the analysis of intact tissues. The potential and the scientific value of TMAs in modern research have been demonstrated in a logarithmically increasing number of studies. The spectrum for additional applications is widening rapidly, and comprises quality control in histotechnology, longterm tissue banking, and the continuing education of pathologists. This review covers the basic technical aspects of TMA production and discusses the current and potential future applications of TMA technology.
PMCID: PMC1187321  PMID: 12890740
tissue microarray; high throughput techniques; quality control
5.  The discovery of the body: human dissection and its cultural contexts in ancient Greece. 
In the first half of the third century B.C, two Greeks, Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, became the first and last ancient scientists to perform systematic dissections of human cadavers. In all probability, they also conducted vivisections of condemned criminals. Their anatomical and physiological discoveries were extraordinary. The uniqueness of these events presents an intriguing historical puzzle. Animals had been dissected by Aristotle in the preceding century (and partly dissected by other Greeks in earlier centuries), and, later, Galen (second century A.D.) and others again systematically dissected numerous animals. But no ancient scientists ever seem to have resumed systematic human dissection. This paper explores, first, the cultural factors--including traditional Greek attitudes to the corpse and to the skin, also as manifested in Greek sacred laws--that may have prevented systematic human dissection during almost all of Greek antiquity, from the Pre-Socratic philosopher-scientists of the sixth and fifth centuries B.C. to distinguished Greek physicians of the later Roman Empire. Second, the exceptional constellation of cultural, political, and social circumstances in early Alexandria that might have emboldened Herophilus to overcome the pressures of cultural traditions and to initiate systematic human dissection, is analyzed. Finally, the paper explores possible reasons for the mysteriously abrupt disappearance of systematic human dissection from Greek science after the death of Erasistratus and Herophilus.
PMCID: PMC2589595  PMID: 1285450
6.  The Toxic Effects of Cigarette Additives. Philip Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation 
PLoS Medicine  2011;8(12):e1001145.
Stanton Glantz and colleagues analyzed previously secret tobacco industry documents and peer-reviewed published results of Philip Morris' Project MIX about research on cigarette additives, and show that this research on the use of cigarette additives cannot be taken at face value.
Background
In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations.
Methods and Findings
We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as “Project MIX.” Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect.
Conclusion
The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The tobacco industry in the United States has recognized that regulation of its products was inevitable as early as 1963 and devoted increasing attention to the likelihood of regulation by the US Food and Drug Administration in the mid-1990s, which finally became law in 2009. In addition, the World Health Organization (WHO) Framework Convention on Tobacco Control (WHO FCTC), which came into force in June 2003, includes provisions addressing the regulation of the contents of tobacco products and the regulation of tobacco product disclosures. Although these steps represent progress in tobacco control, the events of the past few decades show the determination of the tobacco industry to avoid regulation, including the regulation of additives. In the United States, executives of the tobacco company Philip Morris (PM) recognized the inevitability of regulation and responded by initiating efforts to shape legislation and regulation by reorganizing its internal scientific activities and conducting scientific research that could be used to shape any proposed regulations. For example, the company conducted “Project MIX,” a study of chemical constituents in and toxicity of smoke produced by burning cigarettes containing three different combinations of 333 cigarette additives that “were constructed to resemble typical commercial blended cigarettes.” The resulting four papers published in Food and Chemical Toxicology in January 2002 concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied.
Why Was This Study Done?
The use of cigarette additives is an important concern of the WHO, FDA, and similar national regulatory bodies around the world. Philip Morris has used the published Project MIX papers to assert the safety of individual additives and other cigarette companies have done similar studies that reached similar conclusions. In this study, the researchers used documents made public as a result of litigation against the tobacco industry to investigate the origins and design of Project MIX and to conduct their own analyses of the results to assess the reliability of the conclusions in the papers published in Food and Chemical Toxicology.
What Did the Researchers Do and Find?
The researchers systematically examined tobacco industry documents in the University of California San Francisco Legacy Tobacco Documents Library (then about 60 million pages made publicly available as a result of litigation) and used an iterative process of searching, analyzing, and refining to identify and review in detail 500 relevant documents.
The researchers found that in the original Project MIX analysis, the published papers obscured findings of toxicity by adjusting the data by total particulate matter (TPM) concentration. When the researchers conducted their own analysis by studying additives per cigarette (as was specified in the original Project MIX protocol), they found that 15 carcinogenic chemicals increased by 20%. The researchers also reported that, for unexplained reasons, Philip Morris deemphasized 19 of the 51 chemicals tested in the presentation of results, including nine that were substantially increased in smoke on a per cigarette basis of additive-added cigarettes, compared to smoke of control cigarettes.
The researchers explored the possibility that the failure of Project MIX to detect statistically significant changes in the toxicity of the smoke from cigarettes containing the additives was due to underpowered experiments rather than lack of a real effect by conducting their own statistical analysis. This analysis suggests that a better powered study would have detected a much broader range of biological effects associated with the additives than was identified in Philip Morris' published paper, suggesting that it substantially underestimated the toxic potential of cigarette smoke and additives.
The researchers also found that Food and Chemical Toxicology, the journal in which the four Project MIX papers were published, had an editor and 11 of its International Editorial Board with documented links to the tobacco industry. The scientist and leader of Project MIX Edward Carmines described the process of publication as “an inside job.”
What Do These Findings Mean?
These findings show that the tobacco industry scientific research on the use of cigarette additives cannot be taken at face value: the results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes. In addition, better powered studies would probably have detected a much broader range of adverse biological effects associated with the additives than identified to those identified in PM's published papers suggesting that the published papers substantially underestimate the toxic potential combination of cigarette smoke and additives.
Regulatory authorities, including the FDA and similar agencies elsewhere who are implementing WHO FCTC, should conduct their own independent analysis of Project MIX data, which, analyzed correctly, could provide a strong evidence base for the elimination of the use of the studied additives (including menthol) in cigarettes on public health grounds.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001145.
For PLoS Medicine's own policy on publishing papers sponsored by the tobacco industry see http://www.plosmedicine.org/static/policies.action#funders
The World Health Organization (WHO) provides information on the Framework Convention on Tobacco Control (FCTC)
The documents that the researchers reviewed in this paper can be found at the Legacy Tobacco Documents Library
doi:10.1371/journal.pmed.1001145
PMCID: PMC3243707  PMID: 22205885
7.  Testing wound dressings using an in vitro wound model 
Journal of wound care  2010;19(6):220-226.
Objective
To determine whether or not there are any significant differences in the effects of wound dressings on bacterial bioburden.
Method
A selection of non-occlusive, non-adhesive dressings was tested for their effect on bacterial bioburden. The dressings selected included two dressings with antimicrobial properties (one containing silver and one containing PHMB), a cotton-based dressing enclosed in a perforated sleeve of poly(ethylene terephthalate), a carboxymethyl cellulose-based dressing, a fibre-free alginate dressing, and a 12-ply 100% cotton gauze. Using the colony-drip flow reactor (DFR) model, a meticillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa biofilm was grown underneath a dressing sample. Biofilm growth was examined via plate counts, fluorescent microscopy and scanning electron microscopy.
Results
The dressings containing antimicrobial agents had the greatest effect on bacterial load. In the MRSA experiments, both antimicrobial dressings produced lower bacteria counts than the other dressings (p≤0.001), while in the P. aeruginosa experiments, only the silver-containing sample had fewer bacteria (p≤0.0001). However, neither antimicrobial dressing was able to completely eradicate the bacteria when testing with either microorganism.
Conclusion
The results presented herein illustrate that bacteria can grow unchallenged within the dressing environment and that an antimicrobial dressing can limit this bacterial growth.
PMCID: PMC2923929  PMID: 20551862
antimicrobial dressings; biofilms; plate counts; fluorescent microscopy; scanning electron microscopy
8.  Rituals, ceremonies and customs related to sacred trees with a special reference to the Middle East 
Tree worship is very common worldwide. This field study surveys the ceremonies and customs related to sacred trees in present-day Israel; it includes the results of interviews with 98 informants in thirty-one Arab, Bedouin, and Druze villages in the Galilee.
The main results are:
1. Sacred trees were treated as another kind of sacred entity with all their metaphysical as well as physical manifestations.
2. There is not even one ceremony or custom that is peculiar only to a sacred tree and is not performed in other sacred places (such as a saint's grave or a mosque).
3. Few customs, such as: quarrel settling (= Sulkha), leaving objects to absorb the divine blessing and leaving objects for charity) seem to be characteristic of this region, only.
4. In modern times, sacred trees were never recorded, in Israel, as centres for official religious ceremonies including sacrifices, nor as places for the performing of rites of passage.
5. There is some variation among the different ethnic groups: Kissing trees and worshipping them is more common among the Druze although carrying out burials under the tree, leaving water and rain-making ceremonies under them have not been recorded in this group. Passing judgments under the tree is more typical of the Bedouin in which the sacred trees were commonly used as a public social centre.
Most of the customs surveyed here are known from other parts of the world. The differences between Muslims and Druze are related to the latter's belief in the transmigration of souls.
doi:10.1186/1746-4269-3-28
PMCID: PMC1988790  PMID: 17620122
9.  The price of your soul: neural evidence for the non-utilitarian representation of sacred values 
Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.
doi:10.1098/rstb.2011.0262
PMCID: PMC3260841  PMID: 22271790
functional magnetic resonance imaging; sacred values; utility; deontologic; rules
10.  The supernatural characters and powers of sacred trees in the Holy Land 
This article surveys the beliefs concerning the supernatural characteristics and powers of sacred trees in Israel; it is based on a field study as well as a survey of the literature and includes 118 interviews with Muslims and Druze.
Both the Muslims and Druze in this study attribute supernatural dimensions to sacred trees which are directly related to ancient, deep-rooted pagan traditions. The Muslims attribute similar divine powers to sacred trees as they do to the graves of their saints; the graves and the trees are both considered to be the abode of the soul of a saint which is the source of their miraculous powers. Any violation of a sacred tree would be strictly punished while leaving the opportunity for atonement and forgiveness. The Druze, who believe in the transmigration of souls, have similar traditions concerning sacred trees but with a different religious background.
In polytheistic religions the sacred grove/forest is a centre of the community's official worship; any violation of the trees is regarded as a threat to the well being of the community. Punishments may thus be collective.
In the monotheistic world (including Christianity, Islam and Druze) the pagan worship of trees was converted into the worship/adoration of saints/prophets; it is not a part of the official religion but rather a personal act and the punishments are exerted only on the violating individual.
doi:10.1186/1746-4269-3-10
PMCID: PMC1820775  PMID: 17319970
11.  Postmortem and Perimortem Cesarean Section: Historical, Religious and Ethical Considerations 
The Journal of IMA  2012;43(3):194-200.
Guillimeau was the first to use the term cesarean section (CS) in 1598, but this name became universal only in the 20th century. The many theories of the origin of this name will be discussed.
This surgery has been reported to be performed in all cultures dating to ancient times. In the past, it was mainly done to deliver a live baby from a dead mother, hence the name postmortem CS (PMCS). Many heroes are reported to have been delivered this way.
Old Jewish sacred books have made references to abdominal delivery. It was especially encouraged and often mandated in Catholicism. There is evidence that the operation was done in Muslim countries in the middle ages. Islamic rulings support the performance of PMCS.
Now that most maternal deaths occur in the hospital, perimortem CS (PRMCS) is recommended for the delivery of a fetus after 24 weeks from a pregnant woman with cardiac arrest. It is believed that emergent delivery within four minutes of initiation of cardiopulmonary resuscitation (CPR) improves the chances of success of maternal resuscitation and survival and increases the chance of delivering a neurologically intact neonate.
It is agreed that physicians are not to be held legally liable for the performance of PMCS and PRMCS regardless of the outcome. The ethical aspects of these operations are also discussed including a discussion about PMCS for the delivery of women who have been declared brain dead.
doi:10.5915/43-3-7099
PMCID: PMC3516125  PMID: 23610509
Postmortem cesarean section; perimortem cesarean section; history of medicine; medical ethics; Islam; Catholicism; Judaism; brain death
12.  Role of SufI (FtsP) in Cell Division of Escherichia coli: Evidence for Its Involvement in Stabilizing the Assembly of the Divisome▿  
Journal of Bacteriology  2007;189(22):8044-8052.
The function of SufI, a well-studied substrate of the TatABC translocase in Escherichia coli, is not known. It was earlier implicated in cell division, based on the finding that multiple copies of sufI suppressed the phenotypes of cells with mutations in ftsI (ftsI23), which encodes a divisomal transpeptidase. Recently, sufI was identified as both a multicopy suppressor gene and a synthetic lethal mutant of ftsEX, which codes for a division-specific putative ABC transporter. In this study, we show that sufI is essential for the viability of E. coli cells subjected to various forms of stress, including oxidative stress and DNA damage. The sufI mutant also exhibits sulA-independent filamentation, indicating a role in cell division. The phenotypes of the sufI mutant are suppressed by factors that stabilize FtsZ ring assembly, such as increased expression of cell division proteins FtsQAZ or FtsN or the presence of the gain-of-function ftsA* (FtsA R286W) mutation, suggesting that SufI is a divisomal protein required during stress conditions. In support of this, multicopy sufI suppressed the divisional defects of mutants carrying the ftsA12, ftsQ1, or ftsK44 allele but not those of mutants carrying ftsZ84. Most of the division-defective mutants, in particular those carrying a ΔftsEX or ftsI23 allele, exhibited sensitivity to oxidative stress or DNA damage, and this sensitivity was also abolished by multiple copies of SufI. All of these data suggest that SufI is a division component involved in protecting or stabilizing the divisomal assembly under conditions of stress. Since sufI fulfils the requirements to be designated an fts gene, we propose that it be renamed ftsP.
doi:10.1128/JB.00773-07
PMCID: PMC2168700  PMID: 17766410
13.  CICATRIZATION OF WOUNDS  
In the study of the action of non-antiseptic substances on the rate of cicatrization, the chief obstacle encountered is the facility with which wounds become reinfected under an aseptic dressing. At the beginning of Experiment 1 the wound was sterile. It was subjected to flushing with distilled water for 2 hours, then to flushing with 30 per cent sodium chloride solution for another 2 hours. During that time no special precaution was taken to sterilize the wound and the dressing was left intact until the following morning. It was then found that the wound contained from 30 to 50 bacteria per field. The following day, after the wound had been subjected to the same treatment, the number of bacteria had increased to 50 and 100 per field, and as an immediate consequence the surface of the wound increased from 12 to 12.6 sq. cm. in 2 days. The wound was then dressed antiseptically and was found to be sterile 3 days later. Reinfection again took place the following day in spite of antiseptic dressing with chloramine paste 4 parts per 1,000, which was applied for 20 hours. In Experiment 2 similar results were observed. After 2 days of flushing with distilled water, the number of bacteria had increased to 50 per field. The wound was thereupon sterilized, but new reinfection ensued a few days later. Another wound on the same patient became reinfected under the same conditions after 1 day of sterile dressing. In none of the patients could the wounds be kept in a sterile condition throughout the whole experiment. It was impossible to maintain the sterility of a wound under aseptic dressing. Dakin's solution was therefore injected every 4 hours, or less often, according to the degree of infection, or chloramine paste was applied during the night. If there were 3 or 4 bacteria per field, the experiment was discontinued in order that the wound might be sterilized again. The cicatrization and bacteriological curves of Experiment 4 show that by the application of chloramine paste a wound may be maintained in an appropriately bacteriological condition for carrying out an experiment. Nevertheless, in spite of the antiseptic precautions taken, it was necessary to interrupt this experiment on two occasions, on December 13 to 15 and on December 18 to 22, in order that a complete sterilization of the wound might be effected. When the sterilization was performed as soon as the bacteria were discovered, little retardation occurred in the process of cicatrization. Moreover, the reinfection from the skin was often due to fine bacilli which have but mild retarding action on the rate of healing. The use of at least six flushings in 2 hours with Dakin's solution or of 12 hours' dressing with chloramine paste 10 parts per 1,000, was necessary to keep the wound in a condition of surgical asepsis. The action of distilled water was studied in Experiments 1, 2, and 3. In Experiment 1 the wound was subjected to flushing with distilled water first for 2 hours, then 4 hours, and later for 8 hours per day. The wound was maintained in a condition of mild infection. No marked modification, either acceleration or retardation, was noted in the rate of repair during the period that the treatment was applied. From November 21 to 25 the wound was almost clean and the observed curve remained parallel to the calculated curve, showing that distilled water did not retard the rate of healing. In Experiment 2 the wound was subjected to uninterrupted flushing with distilled water, first for 2 and 8 hours, then for 24 hours. It was continued from November 24 to 30; viz., for 112 hours out of 120, without the occurrence of any marked modification of the course of healing. The bacteriological curve showed that from November 22 to 27 inclusive the wound was kept aseptic. The slight retardation which occurred afterwards was probably brought about by the infection. In Experiment 3 the wound was subjected to flushing with distilled water, first for 2, then for 4, 6, and 8 hours, a total of 20 hours in 4 days. From November 21 to 24 the wound remained surgically aseptic. No modification in the rate of healing occurred. The action of the hypertonic sodium chloride solution was studied in a similar way. In Experiment 4 the wound was flushed at first with 40 per cent sodium chloride solution, from December 4 to 9 for 12 hours a day, and from December 10 to 13 for 24 hours a day, making a total of 144 hours out of 240 hours. At the end of this time the surface area of the wound coincided exactly with the calculated area. Owing to reinfection the experiment was suspended. From December 24 to 29 the wound was kept in contact with 50 per cent sodium chloride solution for 54 hours, and after December 30 flushing with 80 per cent solution for 24 hours a day was resorted to. The total amount of time involved in the above treatments was 174 hours with 40 per cent solution, 72 hours with 50 per cent solution, and 120 hours with 80 per cent solution. On January 1, the surface measured 11 sq. cm. and the calculated surface was 11.3 sq. cm. On January 5 the. surface observed was 10 sq. cm. and the calculated surface was 9 sq. cm. It should be noticed that on January 5 the bacteria numbered 4 per field, which might account for the difference. In Experiment 5 the wound was flushed for 24 hours every day with 50 per cent sodium chloride solution from December 11 to 18, a total of 192 hours. From December 18 to 24 the wound was dressed with agar-agar cakes containing 40 per cent sodium chloride. The concentration was raised to 50 per cent from December 24 to 27. The cicatrization curve indicates only a slight retardation of the repair which can be attributed to infection when both cicatrization and infection curves are compared. The temporary acceleration on the 13th may have been due to the influence of the dressing, but as it did not occur again an experimental error is probably the cause of the change observed in the curve. In Experiment 6 two practically identical wounds at a distance of but a few centimeters from each other were located on the right thigh of Patient 721. The areas of the wounds were respectively 40 and 33 sq. cm. One of the wounds was flushed with distilled water only. The other was subjected to the action of 40 per cent sodium chloride solution. From December 20 to 25 both wounds were in a condition of surgical asepsis. However, the cicatrization curves show that in spite of the difference of treatment the rate of healing was not modified. The rate of healing of the wounds did not therefore apparently undergo any measurable modification under the influence of distilled water or hypertonic salt solution. It is well known that the osmotic changes of the medium have a marked influence on tissues deprived of circulation. But it seems that a tissue with normal circulation is protected by it against the changes of the osmotic pressure occurring at its surface. The above experiments show that apparently the conditions of the tissues of a wound are not modified by the changes of the osmotic pressure of the dressing. The beneficial effects of hypertonic sodium chloride solution on the sterilization of wounds and on the rate of healing recently described by various surgeons are possibly an illusion due to lack of precise technique.
PMCID: PMC2125649  PMID: 19868150
14.  Effect of Cargo Size and Shape on the Transport Efficiency of the Bacterial Tat Translocase 
FEBS letters  2013;587(7):912-916.
The Tat machinery translocates fully-folded and oligomeric substrates. The passage of large, bulky cargos across an ion-tight membrane suggests the need to match pore and cargo size, and therefore that Tat transport efficiency may depend on both cargo size and shape. A series of cargos of different sizes and shapes were generated using the natural Tat substrate pre-SufI as a base. Four (of 17) cargos transported with significant (>20% of wild-type) efficiencies. These results indicate that cargo size and shape significantly influences Tat transportability.
doi:10.1016/j.febslet.2013.02.015
PMCID: PMC3613985  PMID: 23422074
secretion; bacteria; inverted membrane vesicles; twin arginine translocation
15.  Collagen Dressing Versus Conventional Dressings in Burn and Chronic Wounds: A Retrospective Study 
Objective:
Biological dressings like collagen are impermeable to bacteria, and create the most physiological interface between the wound surface and the environment. Collagen dressings have other advantages over conventional dressings in terms of ease of application and being natural, non-immunogenic, non-pyrogenic, hypo-allergenic, and pain-free. This study aims to compare the efficacy of collagen dressing in treating burn and chronic wounds with that of conventional dressing materials.
Materials and Methods:
The records of 120 patients with chronic wounds of varied aetiologies and with mean age 43.7 years were collected and analyzed. The patients had been treated either with collagen or other conventional dressing materials including silver sulfadiazine, nadifloxacin, povidone iodine, or honey (traditional dressing material). Patients with co-morbidities that could grossly affect the wound healing like uncontrolled diabetes mellitus, chronic liver or renal disease, or major nutritional deprivation were not included. For the purpose of comparison the patients were divided into two groups; ‘Collagen group’ and ‘Conventional group’, each having 60 patients. For assessment the wound characteristics (size, edge, floor, slough, granulation tissue, and wound swab or pus culture sensitivity results) were recorded. With start of treatment, appearance of granulation tissue, completeness of healing, need for skin grafting, and patients’ satisfaction was noted for each patient in both groups.
Results:
With two weeks of treatment, 60% of the ‘collagen group’ wounds and only 42% of the ‘conventional group’ wounds were sterile (P=0.03). Healthy granulation tissue appeared earlier over collagen-dressed wounds than over conventionally treated wounds (P=0.03). After eight weeks, 52 (87%) of ‘collagen group’ wounds and 48 (80%) of ‘conventional group’ wounds were >75% healed (P=0.21). Eight patients in the ‘collagen group’ and 12 in the ‘conventional group’ needed partial split-skin grafting (P=0.04). Collagen-treated patients enjoyed early and more subjective mobility.
Conclusion:
No significant better results in terms of completeness of healing of burn and chronic wounds between collagen dressing and conventional dressing were found. Collagen dressing, however, may avoid the need of skin grafting, and provides additional advantage of patients’ compliance and comfort.
doi:10.4103/0974-2077.79180
PMCID: PMC3081477  PMID: 21572675
Burns; chronic wounds; collagen dressing
16.  Management of Chronic Pressure Ulcers 
Executive Summary
In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers.
Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series.
Pressure ulcer prevention: an evidence based analysis
The cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation)
Management of chronic pressure ulcers: an evidence-based analysis
Objective
The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions:
Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions?
Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers?
Background
A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health.
The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by as much as 400%, to increase the frequency and duration of hospitalization, and to decrease the quality of life of affected patients. The cost of treating pressure ulcers has been estimated at approximately $9,000 (Cdn) per patient per month in the community setting. Considering the high prevalence of pressure ulcers in the Ontario health care system, the total cost of treating pressure ulcers is substantial.
Technology
Wounds normally heal in 3 phases (inflammatory phase, a proliferative phase of new tissue and matrix formation, and a remodelling phase). However, pressure ulcers often fail to progress past the inflammatory stage. Current practice for treating pressure ulcers includes treating the underlying causes, debridement to remove necrotic tissues and contaminated tissues, dressings to provide a moist wound environment and to manage exudates, devices and frequent turning of patients to provide pressure relief, topical applications of biologic agents, and nutritional support to correct nutritional deficiencies. A variety of adjunctive physical therapies are also in use.
Method
Health technology assessment databases and medical databases were searched from 1996 (Medline), 1980 (EMBASE), and 1982 (CINAHL) systematically up to March 2008 to identify randomized controlled trials (RCTs) on the following treatments of pressure ulcers: cleansing, debridement, dressings, biological therapies, pressure-relieving devices, physical therapies, nutritional therapies, and multidisciplinary wound care teams. Full literature search strategies are reported in appendix 1. English-language studies in previous systematic reviews and studies published since the last systematic review were included if they had more than 10 subjects, were randomized, and provided objective outcome measures on the healing of pressure ulcers. In the absence of RCTs, studies of the highest level of evidence available were included. Studies on wounds other than pressure ulcers and on surgical treatment of pressure ulcers were excluded. A total of 18 systematic reviews, 104 RCTs, and 4 observational studies were included in this review.
Data were extracted from studies using standardized forms. The quality of individual studies was assessed based on adequacy of randomization, concealment of treatment allocation, comparability of groups, blinded assessment, and intention-to-treat analysis. Meta-analysis to estimate the relative risk (RR) or weighted mean difference (WMD) for measures of healing was performed when appropriate. A descriptive synthesis was provided where pooled analysis was not appropriate or not feasible. The quality of the overall evidence on each intervention was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) criteria.
Findings
Findings from the analysis of the included studies are summarized below:
Cleansing
There is no good trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers.
Debridement
There was no evidence that debridement using collagenase, dextranomer, cadexomer iodine, or maggots significantly improved complete healing compared with placebo.
There were no statistically significant differences between enzymatic or mechanical debridement agents with the following exceptions:
Papain urea resulted in better debridement than collagenase.
Calcium alginate resulted in a greater reduction in ulcer size compared to dextranomer.
Adding streptokinase/streptodornase to hydrogel resulted in faster debridement.
Maggot debridement resulted in more complete debridement than conventional treatment.
There is limited evidence on the healing effects of debridement devices.
Dressings
Hydrocolloid dressing was associated with almost three-times more complete healing compared with saline gauze.
There is evidence that hydrogel and hydropolymer may be associated with 50% to 70% more complete healing of pressure ulcers than hydrocolloid dressing.
No statistically significant differences in complete healing were detected among other modern dressings.
There is evidence that polyurethane foam dressings and hydrocellular dressings are more absorbent and easier to remove than hydrocolloid dressings in ulcers with moderate to high exudates.
In deeper ulcers (stage III and IV), the use of alginate with hydrocolloid resulted in significantly greater reduction in the size of the ulcers compared to hydrocolloid alone.
Studies on sustained silver-releasing dressing demonstrated a tendency for reducing the risk of infection and promoting faster healing, but the sample sizes were too small for statistical analysis or for drawing conclusions.
Biological Therapies
The efficacy of platelet-derived growth factors (PDGFs), fibroblast growth factor, and granulocyte-macrophage colony stimulating factor in improving complete healing of chronic pressure ulcers has not been established.
Presently only Regranex, a recombinant PDGF, has been approved by Health Canada and only for treatment of diabetic ulcers in the lower extremities.
A March 2008 US Food and Drug Administration (FDA) communication reported increased deaths from cancers in people given three or more prescriptions for Regranex.
Limited low-quality evidence on skin matrix and engineered skin equivalent suggests a potential role for these products in healing refractory advanced chronic pressure ulcers, but the evidence is insufficient to draw a conclusion.
Adjunctive Physical Therapy
There is evidence that electrical stimulation may result in a significantly greater reduction in the surface area and more complete healing of stage II to IV ulcers compared with sham therapy. No conclusion on the efficacy of electrotherapy can be drawn because of significant statistical heterogeneity, small sample sizes, and methodological flaws.
The efficacy of other adjunctive physical therapies [electromagnetic therapy, low-level laser (LLL) therapy, ultrasound therapy, ultraviolet light therapy, and negative pressure therapy] in improving complete closure of pressure ulcers has not been established.
Nutrition Therapy
Supplementation with 15 grams of hydrolyzed protein 3 times daily did not affect complete healing but resulted in a 2-fold improvement in Pressure Ulcer Scale for Healing (PUSH) score compared with placebo.
Supplementation with 200 mg of zinc three times per day did not have any significant impact on the healing of pressure ulcers compared with a placebo.
Supplementation of 500 mg ascorbic acid twice daily was associated with a significantly greater decrease in the size of the ulcer compared with a placebo but did not have any significant impact on healing when compared with supplementation of 10 mg ascorbic acid three times daily.
A very high protein tube feeding (25% of energy as protein) resulted in a greater reduction in ulcer area in institutionalized tube-fed patients compared with a high protein tube feeding (16% of energy as protein).
Multinutrient supplements that contain zinc, arginine, and vitamin C were associated with a greater reduction in the area of the ulcers compared with standard hospital diet or to a standard supplement without zinc, arginine, or vitamin C.
Firm conclusions cannot be drawn because of methodological flaws and small sample sizes.
Multidisciplinary Wound Care Teams
The only RCT suggests that multidisciplinary wound care teams may significantly improve healing in the acute care setting in 8 weeks and may significantly shorten the length of hospitalization. However, since only an abstract is available, study biases cannot be assessed and no conclusions can be drawn on the quality of this evidence.
PMCID: PMC3377577  PMID: 23074533
17.  Negative Pressure Wound Therapy 
Executive Summary
Objective
This review was conducted to assess the effectiveness of negative pressure wound therapy.
Clinical Need: Target Population and Condition
Many wounds are difficult to heal, despite medical and nursing care. They may result from complications of an underlying disease, like diabetes; or from surgery, constant pressure, trauma, or burns. Chronic wounds are more often found in elderly people and in those with immunologic or chronic diseases. Chronic wounds may lead to impaired quality of life and functioning, to amputation, or even to death.
The prevalence of chronic ulcers is difficult to ascertain. It varies by condition and complications due to the condition that caused the ulcer. There are, however, some data on condition-specific prevalence rates; for example, of patients with diabetes, 15% are thought to have foot ulcers at some time during their lives. The approximate community care cost of treating leg ulcers in Canada, without reference to cause, has been estimated at upward of $100 million per year.
Surgically created wounds can also become chronic, especially if they become infected. For example, the reported incidence of sternal wound infections after median sternotomy is 1% to 5%. Abdominal surgery also creates large open wounds. Because it is sometimes necessary to leave these wounds open and allow them to heal on their own (secondary intention), some may become infected and be difficult to heal.
Yet, little is known about the wound healing process, and this makes treating wounds challenging. Many types of interventions are used to treat wounds.
Current best practice for the treatment of ulcers and other chronic wounds includes debridement (the removal of dead or contaminated tissue), which can be surgical, mechanical, or chemical; bacterial balance; and moisture balance. Treating the cause, ensuring good nutrition, and preventing primary infection also help wounds to heal. Saline or wet-to-moist dressings are reported as traditional or conventional therapy in the literature, although they typically are not the first line of treatment in Ontario. Modern moist interactive dressings are foams, calcium alginates, hydrogels, hydrocolloids, and films. Topical antibacterial agents—antiseptics, topical antibiotics, and newer antimicrobial dressings—are used to treat infection.
The Technology Being Reviewed
Negative pressure wound therapy is not a new concept in wound therapy. It is also called subatmospheric pressure therapy, vacuum sealing, vacuum pack therapy, and sealing aspirative therapy.
The aim of the procedure is to use negative pressure to create suction, which drains the wound of exudate (i.e., fluid, cells, and cellular waste that has escaped from blood vessels and seeped into tissue) and influences the shape and growth of the surface tissues in a way that helps healing. During the procedure, a piece of foam is placed over the wound, and a drain tube is placed over the foam. A large piece of transparent tape is placed over the whole area, including the healthy tissue, to secure the foam and drain the wound. The tube is connected to a vacuum source, and fluid is drawn from the wound through the foam into a disposable canister. Thus, the entire wound area is subjected to negative pressure. The device can be programmed to provide varying degrees of pressure either continuously or intermittently. It has an alarm to alert the provider or patient if the pressure seal breaks or the canister is full.
Negative pressure wound therapy may be used for patients with chronic and acute wounds; subacute wounds (dehisced incisions); chronic, diabetic wounds or pressure ulcers; meshed grafts (before and after); or flaps. It should not be used for patients with fistulae to organs/body cavities, necrotic tissue that has not been debrided, untreated osteomyelitis, wound malignancy, wounds that require hemostasis, or for patients who are taking anticoagulants.
Review Strategy
The inclusion criteria were as follows:
Randomized controlled trial (RCT) with a sample size of 20 or more
Human study
Published in English
Summary of Findings
Seven international health technology assessments on NPWT were identified. Included in this list of health technology assessments is the original health technology review on NPWT by the Medical Advisory Secretariat from 2004. The Medical Advisory Secretariat found that the health technology assessments consistently reported that NPWT may be useful for healing various types of wounds, but that its effectiveness could not be empirically quantified because the studies were poorly done, the patient populations and outcome measures could not be compared, and the sample sizes were small.
Six RCTs were identified that compared NPWT to standard care. Five of the 6 studies were of low or very low quality according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. The low and very low quality RCTs were flawed owing to small sample sizes, inconsistent reporting of results, and patients lost to follow-up. The highest quality study, which forms the basis of this health technology policy assessment, found that:
There was not a statistically significant difference (≥ 20%) between NPWT and standard care in the rate of complete wound closure in patients who had complete wound closure but did not undergo surgical wound closure (P = .15).
The authors of this study did not report the length of time to complete wound closure between NPWT and standard care in patients who had complete wound closure but who did not undergo surgical wound closure
There was no statistically significant difference (≥ 20%) in the rate of secondary amputations between the patients that received NPWT and those that had standard care (P = .06)
There may be an increased risk of wound infection in patients that receive NPWT compared with those that receive standard care.
Conclusion
Based on the evidence to date, the clinical effectiveness of NPWT to heal wounds is unclear. Furthermore, saline dressings are not standard practice in Ontario, thereby rendering the literature base irrelevant in an Ontario context. Nonetheless, despite the lack of methodologically sound studies, NPWT has diffused across Ontario.
Discussions with Ontario clinical experts have highlighted some deficiencies in the current approach to wound management, especially in the community. Because NPWT is readily available, easy to administer, and may save costs, compared with multiple daily conventional dressing changes, it may be used inappropriately. The discussion group highlighted the need to put in place a coordinated, multidisciplinary strategy for wound care in Ontario to ensure the best, continuous care of patients.
PMCID: PMC3379164  PMID: 23074484
18.  Attempting to demystify law reports for the non-lawyer. 
Journal of Medical Ethics  1988;14(1):35-37.
To a non-lawyer, references to law reports can appear confusing and complicated. This brief article attempts to explain how to decode such references and thus get to the reports. Those wishing to pursue the matter further are referred to more detailed explanations. This article deals primarily with English case law and is up to date as of December 1987.
PMCID: PMC1375526  PMID: 3351882
19.  Helicobacter pylori Therapy Demystified 
Helicobacter  2011;16(5):343-345.
We discuss the role of comparators in H. pylori treatment trials and why design of an anti-H. pylori therapeutic trial for an infectious disease is fundamentally different from that of common gastrointestinal diseases (eg, the absence of a placebo response, the expectation that cure rates in excess of 95% are routinely possible, and the ability to understand why treatment fails). No comparator is absolutely required other than to 100% success; comparison trials should be limited to comparisons between therapies that reliably achieve 90% or greater success (i.e., good therapies). Comparisons to known low success regimens (i.e., bad therapies) are unethical as is withholding information from the subject regarding current effectiveness of a regimen even if that information would reduce the likelihood that the subject would volunteer. We also discuss how it is possible to predict the outcome of a published but locally untried new regimen. The reason for different outcomes of typical gastrointestinal therapies is shrouded in mystery. In contrast, treatment success for H. pylori should be predictable and treatment failures explainable. For too long expectations and analyses of H. pylori therapy has been confused with what is appropriate for gastrointestinal disease such as constipation or irritable bowel syndrome rather than for infectious diseases such as pneumonia.
doi:10.1111/j.1523-5378.2011.00891.x
PMCID: PMC3318913  PMID: 21923679
20.  Demystified … Nitric oxide 
Molecular Pathology  2002;55(6):360-366.
The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease.
PMCID: PMC1187271  PMID: 12456772
21.  Demystified … Molecular pathology in oncology 
Molecular Pathology  2002;55(6):337-347.
In the past 10 years, molecular biology has found major applications in pathology, particularly in oncology. This has been a field of enormous expansion, where pure science has found a place in clinical practice and is now of everyday use in any academic unit. This demystified review will discuss the techniques used in molecular pathology and then provide examples of how these can be used in oncology.
PMCID: PMC1187267  PMID: 12456768
molecular pathology; oncology; polymerase chain reaction; fluorescent in situ hybridisation; Southern blotting; microarray analysis
22.  One Approach to Demystifying Research in Primary Care 
Canadian Family Physician  1989;35:871-944.
“Research” means different things to different people. “Organized curiosity” has been proposed as a suitable description for family-practice research. Studies involving patients in community practices are becoming recognized as a unique type of research that contributes new understanding to matters relating to primary care. Such research, however, requires an infrastructure that makes a study as unobtrusive as possible in participating practices. One approach is the development of a primary care research unit (PCRU): a central co-ordinating communications office which can provide the human and technical resources needed to assist each community office with protocol and data-collection steps. The author of this article describes the functional components of a PCRU in five groupings: namely, technical, human, communication and support systems, a network of community physicians, and facilities. Finally, several important principles about funding primary care research are suggested.
PMCID: PMC2280850  PMID: 21249035
family practice; research; primary care research unit
23.  Demystifying the NIH Grant Application Process 
Journal of General Internal Medicine  2007;22(11):1587-1595.
The process of applying to the National Institutes of Health (NIH) for grant funding can be daunting. The objective of this article is to help investigators successfully navigate the NIH grant application process. We focus on the practical aspects of this process, which are commonly learned through trial and error. Our target audience is generalist faculty and fellows who are applying for NIH funding to support their career development or a clinical research project.
doi:10.1007/s11606-007-0301-6
PMCID: PMC2219790  PMID: 17687616
clinical research; academic medicine; NIH; funding; grants
24.  Demystified … 
Molecular Pathology  2001;54(1):1-7.
The basic physiology of leucocyte emigration from the intravascular space into the tissues is now known to be dependent on a class of cell surface molecules that have come to be known as adhesion molecules. Many cell–cell interactions are dependent on adhesion and signal transduction via the various adhesion molecules, particularly the integrins. The study of the functions of these molecules has been enhanced by the development of blocking and activating monoclonal antibodies, knockout mice, and by the rare “experiments of nature” in the human population, in whom there is absence or dysfunction of one of the adhesion molecules. This review describes these leucocyte adhesion defects and discusses how they have provided important insights into the function of these molecules.
PMCID: PMC1186993  PMID: 11212883
leucocyte adhesion defect; Glanzmann's thrombasthenia; integrins
25.  Glycerin-Based Hydrogel for Infection Control 
Advances in Wound Care  2012;1(1):48-51.
Problem
Infection is a major problem in the health and wellbeing of patients in hospitals, nursing homes, and other medical facilities as well as the homecare patients and the general public. According to Scientia Advisors, wound care costs the healthcare system over $7 billion in 2009. After adding the cost associated with potential complications such as infections, extended physician care, and lengthy hospital stays, the annual wound care expenditures well exceeded over $20 billion.1 There are 20 million reported cases of diabetes per year and more every day. Because of the fact that leg ulcers are the number one health problem of men coupled with the rise in drug resistance of infections, the importance of providing the professional and the public with relatively simple and affordable wound care is of extreme importance. Often the wounds can become chronic wounds, which then result in long-term nursing expense in time and supplies or, worse yet, can result in expensive amputations ranging from $5000 to $40,000 per patient.
Solution
There are many dressing options now available for treating wounds with components such as glycerin, honey, salt, and many other natural products, with some dressings being more appropriate than others. In 1988, a patented glycerin-based dressing was introduced to the market, called Elasto-Gel™.2
New Technology
Elasto-Gel™ is a glycerin-based gel sheet (65%) combined with a hydrophilic polymer that causes the sheet to absorb the exudate from the wound and simultaneously release the glycerin from the gel, which adds many benefits to the wound for excellent healing outcomes. The gel sheet is 1/8th of an inch thick with a four-way stretch backing. It has the ability to absorb 3–4 times its own weight of fluids. The dressing will not dry out or allow the exudate to dry out, thus keeping the dressing from becoming bonded to the wound or the surrounding tissue. It does not have adhesive properties and, therefore, will not cause damage to the wound bed or periwound area upon dressing removal. Because of the thickness, the product provides excellent cushion and padding support. It has been also proven to be bacteriostatic/fungistatic. (Bacteriostatic is the ability to restrain the development or reproduction of bacteria.3)
Product Technology
Glycerin is a huamectant by definition and has been recognized by the U.S. Food and Drug Administration (FDA). Humectants attract, bind, and hold moisture to the site of application. The actual concentration of glycerin in a wound dressing is indicative of the ability to absorb excess moisture. Exudate management is an important function of topical treatment. The ability to absorb drainage and prevent pooling of exudate in the wound or on the surrounding skin are attributes specific to high glycerin content. Perhaps, the most significant advantage of the glycerin-based hydrogel sheet is its impact on wound bioburden and pathogenic organisms.4 Glycerin is a simple three-carbon tri-alcohol and is a natural humectant. It is used as a carrier in many medicines and as plasticizer in gelatin gel capsules. Glycerin is a component of cosmetics, conditioners, soaps, foods, and other common products. It is a component of mono-, di-, and triglycerides naturally occurring in the body. These glycerides and glycerin are constantly reacted with each other by the natural enzymes and reversed with the natural metabolic processes already present in the body. Any glycerin that may be absorbed into the body fluid is rapidly diluted in these fluids and is no longer toxic but is metabolized as another component of the food chain. It is well known that glycerin in high concentration will exhibit dehydrating effect on many systems including living cells by the commonly known process of osmosis. (Osmosis: the flow or diffusion that takes place through a semipermable membrane, as of living cell, typically separating a solvent such as water, thus bringing about equilibrium conditions.5) It has been shown that glycerin at high concentration will be cytotoxic to all cells that have been tested if they are exposed long enough. These properties of glycerin have been recognized by the European Skin Bank, where they use 85% glycerin solutions to store cadaver skin at ∼42F, and can be used for potential wound coverings. The cadaver skin that has been prepared by this method has been available since 1994.6 The concern for safety resulted in a three-day international synmposium7 with emphasis on glycerin-preserved cadaver skin providing healthy environment for the preserved skin to be successfully accepted without rejection, having no complications of infection and providing excellent healing outcomes and minimal scaring. Additional research by Dr. David P. Mackie of the Red Cross Hospital, The Netherlands, reported that using 85% glycerin solutions had slow bactericidal effects and also showed virocidal activity on several types of viruses.8 Dr. Hoekstra has observed that within 2 hours after application of Elasto-Gel™, the inflammatory reaction is reduced.9 Vandeputte, Belgium, showed that wounds covered with Elasto-Gel™ had fewer myofibroblasts than those covered with hydrocolloid.10 It has been proposed that myofibroblasts in high concentrations contribute to the formation of hypertrophic and keloid scars. As noted earlier, there is less scar formation when glycerin-based gel sheets are used. The data sited here have shown that glycerin and glycerin-based products are effective antimicrobial agents with less side effects. Many verbal reports along with personal communications have indicated that applying glycerin-based gel sheets to stalled wounds, some 15–20-year-old chronic wounds, resulted in healing in 1–20 weeks (data/case studies on file).
Indications for Use
Elasto-Gel™ has been approved for all types of wounds, that is, pressure ulcers, acute and chronic wounds, diabetic wounds, traumatic wounds, dermatology wounds, cancer tumors, and first- and second-degree burns, to name a few. Because of the product's features and benefits, it may be used on a variety of wounds. Because of its padding properties, it may be also used as a preventative product over bony prominence areas so that wounds do not occur. The glycerin properties act as a skin substitute and may also be used for scar reduction.
Caution
Elasto-Gel™ is not approved for third-degree burns as no dressing has been approved by the FDA for this type of wound.
doi:10.1089/wound.2011.0288
PMCID: PMC3839013  PMID: 24527279

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