In 2009, Target Health Inc. established the Target Health Global Partnership (THGP) to facilitate global clinical research. The goal of the partnership is to bring together the “best of the best” small to mid-size companies from all corners of the world to offer the most sophisticated and experienced approaches to drug, biologic and device development. The THGP combines the passion, efficiency and speed of the entrepreneurial spirit with those who really care about what they do. In addition, projects driven by the partnership share one paperless clinical trial software platform so there is no need to use different software products across regions and studies.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website,

 

 

High-1) ___, but not low-dose, zinc lozenges shorten the duration of the common cold, according to the results of a meta-analysis reported in the July 2011 issue of The Open Respiratory Medicine Journal.

 

“A number of controlled trials have examined the effect of zinc 2) ___ on the common cold but the findings have diverged,” writes Harri Hemila, MD, PhD, from the Department of Public Health, University of Helsinki, in Helsinki, Finland. “The purpose of this study was to examine whether the total daily dose of zinc might explain part of the variation in the results.” To identify placebo-controlled trials assessing the effect of zinc lozenges on common 3) ___ duration, Dr. Hemila searched MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. All of the identified trials were analyzed together, and the low-dose 4) ___ and high-dose zinc trials were analyzed separately. The Fisher method was used to combine the P values of the trials, and the inverse-variance method allowed pooling of trial data.

 

The literature search identified 13 placebo-controlled comparisons evaluating the therapeutic effect of zinc lozenges on the duration of common cold episodes of natural origin. The 5 trials using a total daily zinc dose of less than 75 mg found no effect on common cold duration, whereas pooled data from 3 trials using zinc acetate in daily doses exceeding 75 mg showed a 42% reduction in the duration of colds. The remaining 5 trials used zinc salts other than 5) ___ in daily doses exceeding 75 mg, and pooled analysis of these data showed a 20% reduction in the duration of colds.

 

“This study shows strong evidence that the zinc lozenge effect on common cold duration is heterogeneous so that benefit is observed with high doses of zinc but not with 6) ___ doses,” Dr. Hemila writes. “The effects of zinc lozenges should be further studied to determine the optimal lozenge compositions and treatment strategies.” Limitations of this meta-analysis include those inherent in the included studies.

 

“On the basis of these long-term studies with 7) ___high zinc doses, there does not seem to be any basis for assuming that treating the common cold for a week with high doses of zinc in the form of lozenges would cause unanticipated harm,” Dr. Hemila concludes. “A patient suffering from acute adverse effects such as bad taste can simply 8) ___stop taking the lozenges.”

 

ANSWERS: 1) dose; 2) lozenges; 3) cold; 4) zinc; 5) acetate; 6) low; 7) high; 8) stop

Oral Hygiene

 

 

 

The earliest known reference to a toothpaste is in a manuscript from Egypt in the 4th century CE, which prescribes a mixture of powdered salt, pepper, mint leaves, and iris flowers. The Romans used toothpaste formulations based on human urine. Since urine contains ammonia, it was probably effective in whitening teeth. The Greeks, and then the Romans, improved the recipes for toothpaste by adding abrasives such as crushed bones and oyster shells.

 

In the 9th century, the Persian musician and fashion designer Ziryab invented a type of toothpaste, which he popularized throughout Islamic Spain. The exact ingredients of this toothpaste are unknown,but it was reported to have been both “functional and pleasant to taste.”  It is not known whether these early toothpastes were used alone, were to be rubbed onto the teeth with rags, or were to be used with early toothbrushes, such as neem-tree twigs and miswak.

 

Botot toothpaste is considered the “world’s first toothpaste.” Dr. Julien Botot invented this toothpaste in 1755 for King Louis XV of France. The formula lacks any of those nasty synthetic ingredients or colors. Instead it contains special natural ingredients like gillyflower, ginger, and cinnamon that give your mouth a slight warming feeling while promoting circulation in your gums. It tastes and feels like the first couple of chews of Big Red gum.  Dr. Julien Botot, an 18th century physician, cared for the French King Louis XV, and developed for him oral hygiene products such as a toothpaste and mouthwash. The figure in the top-left ad, is one that is easily recognizable to the French as the doctor from Moliere’s play The Imaginary Invalid.

 

Toothpastes or powders did not come into general use until the 19th century. In the early 1800s, the toothbrush was usually used only with water, but tooth powders soon gained popularity. Tooth powders for use with toothbrushes came into general use in the 19th century in Britain. Most were homemade, with chalk, pulverized brick, or salt as ingredients. An 1866 Home Encyclopedia recommended pulverized charcoal, and cautioned that many patented tooth powders that were commercially marketed did more harm than good. An 18th century American and British toothpaste recipe called for burnt bread. Another formula around this time called for dragon’s blood (a resin), cinnamon, and burnt alum.

 

By 1900, a paste made of hydrogen peroxide and baking soda was recommended for use with toothbrushes. Pre-mixed toothpastes were first marketed in the 19th century, but did not surpass the popularity of tooth-powder until World War I. In 1892, Dr. Washington Sheffield of New London, Connecticut, manufactured toothpaste into a collapsible tube, Dr. Sheffield’s Creme Dentifrice. He had the idea after his son traveled to Paris and saw painters using paint from tubes. In New York City in 1896, Colgate & Company Dental Cream was packaged in collapsible tubes imitating Sheffield. The original collapsible toothpaste tubes were made of lead.  Colgate also made a tooth powder sold in a bottle-shape tin, used during and after World War 2, see the top right graphic.  Directions were to, sprinkle some powder into your hand; wet your toothbrush and push the wet bristles into the powder, creating a paste, which you then brushed your teeth with.

 

Fluoride was first added to toothpastes in 1914, and was initially criticized by the American Dental Association (ADA) in 1937. Fluoride toothpastes developed in the 1950s received the ADA’s approval. To develop the first ADA-approved fluoride toothpaste, Procter & Gamble started a research program in the early 1940s. In 1950, Procter & Gamble developed a joint research project team headed by Dr. Joseph Muhler at Indiana University to study new toothpaste with fluoride. In 1955, Procter & Gamble’s Crest launched its first clinically proven fluoride-containing toothpaste. On August 1, 1960, the ADA reported that “Crest has been shown to be an effective anticavity (decay preventative) dentifrice that can be of significant value when used in a conscientiously applied program of oral hygiene and regular professional care.” The amount of fluoride in toothpastes varies from country to country.

Horse Versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia

 

 

Aplastic anemia is a rare disorder, newly diagnosed in approximately 1,000 patients in the US every year. The disease destroys bone marrow and severely lowers the number of functional blood cells in the body. This can lead to anemia, hemorrhaging, and increased risk of infections. It is often fatal if not successfully treated. There are multiple causes of aplastic anemia, including toxic exposures, irradiation, inherited diseases, and autoimmune damage, often following an infection such as hepatitis.

 

In severe acquired aplastic anemia, hematopoietic failure is the result of immune-mediated destruction of bone marrow stem and progenitor cells. Immunosuppressive therapy with antithymocyte globulin (ATG) plus cyclosporine is an effective alternative to stem-cell transplantation and improves blood counts and survival. Although horse ATGAM (lymphocyte immune globulin, anti-thymocyte globulin, equine) is the standard therapy, rabbit ATG (Thymoglobulin; Genzyme) is more potent in depleting peripheral-blood lymphocytes and is preferred in other clinical circumstances. Thymoglobulin is not yet licensed for aplastic anemia in the US. However, it has been reported to be effective when used in patients who don’t respond or who relapse following ATGAM treatment. In addition, Thymoglobulin is the only aplastic anemia option available in Europe, Japan, and Latin America. Thus, the findings of this study have implications for management of this disorder internationally.

 

According to an article published in the New England Journal of Medicine (2011; 365:430-438) a randomized clinical trial was performed comparing these two ATG formulations in conventional regimens. Patients were treated at a single facility. The primary outcome was hematologic response at 6 months, as determined by blood counts. The study was designed to enroll 60 patients each for the rabbit-ATG and horse-ATG groups and was powered to detect a difference of 25% in the response rate.

 

Results showed that horse ATGAM, currently the only licensed aplastic anemia drug in the US, improved blood cell counts and survival significantly more than Thymoglobulin. Six months after starting treatment, 68% of patients given horse ATGAM had improved levels of red blood cells, white blood cells, and platelets, compared to 37% of patients given Thymoglobulin. In terms of survival, after three years, 96% of ATGAM patients were alive, compared to 76% of Thymoglobulin patients.

 

According to the authors, the study suggests that ATGAM should remain the first-line regimen of choice in treating severe aplastic anemia. The authors added that this important finding may affect the future treatment of aplastic anemia, particularly in places like Europe where ATGAM is not currently used.  It may also inspire further studies that compare horse and rabbit ATG to better understand how ATG helps restore bone marrow. Since some patients responded very well to Thymoglobulin and others responded poorly to ATGAM, future work might identify the optimal ATG treatment for specific patient subgroups.

The Effect Text-Message Reminders on Malaria Control

 

 

Health workers’ malaria case-management practices often differ from national guidelines. As a result, a study published online in The Lancet (4 August 2011) was performed to assess whether text-message reminders sent to health workers’ mobile phones could improve and maintain their adherence to treatment guidelines for outpatient pediatric malaria in Kenya.

 

From March 6, 2009, to May 31, 2010, a cluster-randomized controlled trial was performed at 107 rural health facilities in 11 districts in coastal and western Kenya. With a computer-generated sequence, health facilities were randomly allocated to either the intervention group, in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months, or the control group, in which health workers did not receive any text messages. Health workers were not masked to the intervention, although patients were unaware of whether they were in an intervention or control facility. The primary outcome was correct management of treatment with the antimalarials artemether-lumefantrine (Coartem), defined as a dichotomous composite indicator of treatment, dispensing, and counseling tasks concordant with Kenyan national guidelines. The primary analysis was by intention to treat.

 

During the study, 119 health workers received the intervention. Case-management practices were assessed for 2,269 children who needed treatment (1,157 in the intervention group and 1,112 in the control group). Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23.7% (p=0.004) immediately after intervention and by 24.5% (p=0.003) 6 months later.

 

According to the authors, in resource-limited settings, malaria control programs should consider use of text messaging to improve case-management practices of health workers.

Cytomegalovirus Load in Inflamed Intestinal Tissue Is Predictive of Resistance to Immunosuppressive Therapy in Ulcerative Colitis

 

 

Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. As a result, a study published online in the American Journal of Gastroenterology (26 July 2011) evaluated the use of CMV DNA load in intestinal tissue during acute flare-ups of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy.

 

For the study, 42 consecutive patients (gender ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were evaluated prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines.

Results showed that 16 patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue. All of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7). A CMV DNA load above 250?copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+ = 4.33). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir. A clinical remission was observed in seven cases, with a sustained response in five.

 

According to the authors, the CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC and that initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

 

 

FDA Approves First Specific Treatment for Scorpion Stings

 

 

 

Venomous scorpions in the U.S. are mostly found in Arizona. Severe stings occur most frequently in infants and children, and can cause shortness of breath, fluid in the lungs, breathing problems, excess saliva, blurred vision, slurred speech, trouble swallowing, abnormal eye movements, muscle twitching, trouble walking, and other uncoordinated muscle movements. Untreated cases can be fatal.

 

The FDA has approved Anascorp, the first specific treatment for a scorpion sting by Centruroides scorpions in the United States. Anascorp, Centruroides (Scorpion) Immune F(ab’)2 (Equine) Injection, is made from the plasma of  horses immunized with scorpion venom. Anascorp may cause early or delayed allergic reactions in people sensitive to horse proteins. The manufacturing process for Anascorp includes steps to decrease the chance of allergic reactions and to reduce the risk of transmission of viruses that may be present in the plasma.

 

The effectiveness of Anascorp was based on results from a randomized, double-blind, placebo-controlled trial of 15 children with neurological signs of scorpion stings. These signs resolved within four hours of treatment in the eight subjects who received Anascorp, but in only one of the seven participants who received the placebo. The most common side effects were vomiting, fever, rash, nausea, itchiness, headache, runny nose, and muscle pain. In total, safety and efficacy data was collected from 1,534 patients in both open-label and blinded studies.

 

Anascorp was designated as an Orphan drug by FDA and received priority review. It is licensed to Rare Disease Therapeutics Inc., Franklin, TN, distributed by Accredo Health Group Inc., Memphis, TN, and manufactured by Instituto Bioclon, S.A. de C.V., of Tlalpan, Mexico, D.F.

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing.

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1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

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