UTRECHT, The Netherlands, Aug. 17 — Fosamax (alendronate) proved more effective than a vitamin D3 analogue in preventing glucocorticoid-induced bone loss in patients treated for rheumatic diseases, according to researchers here.

An 18-month study found a 4% difference in bone-mineral density of the lumbar spine favoring Fosamax (alendronate) over alfacalcidol, a vitamin D3 analogue, Ron de Nijs of University Medical Center Utrecht, and colleagues, reported in the Aug. 17 issue of the New England Journal of Medicine.

Active vitamin D3 analogues, such as alfacalcidol, stimulate the formation and action of osteoblasts, whereas bisphosphonates, such as Fosamax, induce apoptosis of osteoclasts and inhibit bone resorption, the researchers wrote.

In the randomized double-placebo, double-blind trial, 201 patients with rheumatic diseases started glucocorticoid therapy at a daily dose equivalent to at least 7.5 mg of prednisone. The mean cumulative glucocorticoid doses during the study were 5,790 mg ?± 3,663 mg in the Fosamax group and 5,704 mg ?± 3375 mg in the alfacalcidol group, a difference of 86 mg.

One third of the patients had rheumatoid arthritis, one third had polymyalgia, while the rest had another rheumatic disease, the researchers said.

Patients from 23 outpatient clinics in the Netherlands were randomized to 10 mg of Fosamax and a placebo capsule of alfacalcidol daily or alfacalcidol (1??g) and a placebo tablet of Fosamax daily.

At 18 months, the bone-mineral density of the lumbar spine increased by 2.1% in the Fosamax group (95% confidence interval, 1.1% to 3.1%) but decreased by 1.9% in the alfacalcidol group (CI, -3.1% to -0.7 %). The mean difference of change in bone mineral density between the two groups was 4.0% (CI, 2.4% to 5.5%), the researchers reported.

Changes in bone mineral density at other sites — femoral neck, total hip — were similar. For example, density at the femoral neck increased 1.4% in the Fosamax group and decreased 2.0% in the alfacalcidol group, for an absolute difference of 3.4% (CI, 1.3% to 5.5%), the researchers reported.

Although there were more new vertebral deformities in the alfacalcidol group compared with the Fosamax patients, the difference was not significant, the researcher said.

Three Fosamax patients had a new vertebral deformity, compared with eight alfacalcidol patients with 13 new deformities, of which five were symptomatic in three patients (hazard ratio, 0.4; CI, 0.1 to 1.4).

Further, two Fosamax patients had actual fractures, one in the midfoot and another of the forearm. In the alfacalcidol group, the three fractures included one of the femoral neck, one of the pubic bone, and one of a rib, the researchers reported.

There were few side effects for either treatment, the researchers wrote. Adverse event for the Fosamax group included hypercalcemia in three patients versus seven in the alfacalcidol group. In one Fosamax patient, calcium supplementation was stopped because of hypercalcemia, but no reduction in the dose of alfacalcidol was necessary because serum calcium became normal. There was no report of thyroid or renal dysfunction during the study.

Because of logistic difficulties, the researcher said they were not able to measure 24-hour urinary calcium, although hypercalciuria is often found in patients receiving active vitamin D3 metabolites. Therefore, they suggested, that in addition to measuring serum calcium levels, urinary calcium monitoring may be necessary for safety reasons in patients receiving vitamin D3.

According to the investigators, Merck provided matched Fosamax and placebo tablets. Teva Pharmaceuticals provided matched alfacalcidol and placebo capsules. Dr. de Nijs reported having received grant support from the Dutch Health Care Insurance Board, while other investigators reported consulting or lecture fees from Eli Lilly, Merck, Procter & Gamble; Chiron Vaccines, Baxter, Organon, Janssen-Cilag, Wyeth, Abbott, Novartis, Roche, Sanofi-Aventis, and Schering-Plough.

Primary source: New England Journal of Medicine

Source reference:
de Nijs, RNJ, et al “Alendronate or Alfacalcidol in Glucocorticoid-Induced Osteoporosis” N Engl J Med 2006; 355:675-684.

CHICAGO, June 27 — Dapaglifozin, a novel investigational antidiabetic agent that increases excretion of glucose in urine, appeared safe and effective in early clinical trials, researchers reported here.

In a randomized double-blind study, dapagliflozin in each of three doses significantly increased the excretion of excess glucose in urine compared with placebo, reported Bernard Komoroski, PharmD., Ph.D., an investigator for drug-maker Bristol-Myers Squibb, at the American Diabetes Association meeting.

The drug seemed to be well tolerated. Although there were two case of hypoglycemia, both occurred in patients also taking metformin (Glucophage) after a long fast, Dr. Komoroski said.

Dapagliflozin (BMS-512148), developed jointly by Bristol-Myers Squibb and AstraZeneca, is the first drug to reach clinical trials in a new category of agents, called selective inhibitors of the sodium-glucose uptake transporter 2 (SGLT2).

The novel action in this class involves inhibition of glucose reabsorption in the proximal renal tubule, although glucose reabsorption still occurs farther downstream in the kidney, Dr. Komoroski said.

In animal studies, SGLT2 inhibition activity modulated reabsorption of glucose by the kidney, causing the excess glucose to be excreted in urine. The end result is a decrease in serum glucose independent of either insulin secretion or insulin action.

The investigators conducted a phase II study in 47 adults with type 2 diabetes. The patients, ages 18 to 77, were all either na??ve to antidiabetic agents, or on a stable dose of metformin for at least four weeks before randomization.

Baseline glycosylated hemoglobin (HbA1c) levels ranged from 6% to 10%, and the patients had fasting serum glucose levels of 240 mg/dL or less.

The participants were randomized to receive either placebo (eight patients) or dapagliflozin at doses of 5 mg (11 patients), 25 mg (12 patients), or 100 mg (16 patients) once daily for two weeks. The drugs were taken in addition to the patients’ stable metformin dose or diet. The study was conducted with patients staying in an inpatient clinical research unit.

The primary outcomes were safety and tolerability of multiple doses of dapagliflozin. Secondary endpoints included fasting serum glucose, and post-challenge glucose excursions.

The authors found that on day 13, the fasting serum glucose was significantly reduced in participants receiving dapagliflozin with or without metformin, compared with levels measured two days before they received their first doses.

Among patients on the 5 mg dose there was a 14.5% reduction in fasting serum glucose (P

LEXINGTON, Ky., Nov. 17 – A new antibody profiling technique can diagnose non-small cell lung cancer (NSCLC) with extreme accuracy, researchers said here.

A combination of five antibodies associated with NSCLC can be used to find the disease almost 90% of the time, with only a 5% false-positive rate, according to Li Zhong, Ph.D., of the University of Kentucky’s Chandler Medical Center.

Tested against a separate group of normal participants and cancer patients, the five markers combined showed a diagnostic accuracy of 89.9% — greater than even the best of the single marker tests, Dr. Zhong said.

“Much emphasis [for NSCLC] has been placed on the discovery and characterization of unique tumor markers.” But so far, he said, no one has been able to show that a single biochemical marker can be used reliably to diagnose the disease in its early stages, when it is most easily cured, although several such single-marker tests are clinically available.

To overcome that obstacle, “we have been exploring methodology for efficiently identifying and measuring multiple tumor-associated antibodies,” Dr. Zhong and colleagues reported in the Nov. 15 edition of the American Journal of Respiratory and Critical Care Medicine.

Using micro-array technology and T7 phage display libraries, the researchers tested more than 4,000 proteins by comparing samples from normals and patients with NSCLC.

They identified seven proteins via statistical analysis that were significantly different (p

SAN ANTONIO — Low-dose quinidine in combination with dextromethorphan reduces the frequency of uncontrollable laughing or crying in multiple sclerosis while improving patient safety, according to research presented here.

Using just a third of the quinidine dose contained in the current combination therapy, marketed as Zenvia, reduced those episodes by more than half, compared with a decrease of about one a day with placebo (P=0.0280), Daniel Wynn, MD, of Consultants in Neurology in Northbrook, Ill., and colleagues found.

Pseudobulbar affect (PBA), characterized by laughing or crying outbursts incongruent with the patient’s emotional state, affects 15% of patients with MS, and is also seen in ALS, Alzheimer’s disease, and other neurologic diseases.

“Pseudobulbar affect causes considerable distress for patients and caregivers,” Wynn told attendees at the meeting of the Joint Consortium of Multiple Sclerosis Centers and America’s Committee on Treatment and Research in Multiple Sclerosis. “It can be extremely socially disabling, and it is often under-recognized and undertreated.”

Previous studies established that 30 mg of dextromethorphan in combination with 30 mg of quinidine effectively treated the condition, leading to FDA approval of the combination therapy. “The efficacy was extremely well established in previous trials,” Wynn said. But ongoing concerns about the adverse effects of quinidine prompted researchers to try a reduced dose for an improved safety profile.

Dextromethorphan is an NMDA receptor antagonist as well as a sigma receptor agonist, and is responsible for the drug’s clinical benefit. Quinidine is a CYP2D6 inhibitor, added to prevent metabolism of dextromethorphan. High doses of quinidine are associated with prolongation of the QT interval.

The dose in the current trial, 10 mg, “is truly miniscule,” Wynn said.

To determine if the reduced dose was still effective for PBA, Wynn and colleagues enrolled 326 patients, including 129 with MS, at 64 centers in three countries.

Patients were randomized 1:1:1 to either the standard dose of dextromethorphan 30 mg and 10 mg of quinidine, a lower dextromethorphan dose of 20 mg and the 10 mg of quinidine, or placebo, twice a day for 12 weeks.

The primary outcome variable was change in the number of laughing or crying episodes per day. Secondary outcomes included change in the Center for Neurologic Studies Lability Scale (CNS-LS), and a pain score.

At baseline, MS patients averaged between three and four episodes of laughing or crying per day.

Active treatment with the higher dose dextromethorphan and the low dose of quinidine reduced those episodes by 2.7 per day, compared with just over one per day for MS patients receiving placebo (P=0.0280).

There was no significant effect from lower-dose dextromethorphan, but there was a trend for superiority when both active treatment groups were compared together against placebo.

The CNS-LS score in MS patients was also improved by the 30 mg dextromethorphan/10 mg quinidine dose versus placebo, falling by approximately 50% in active-treatment patients versus 33% in placebo patients.

Change on pain score was not significantly different between groups, but a post-hoc analysis of MS patients with significant baseline pain indicated that the high-dose, but not low-dose dextromethorphan improved pain relative to placebo.

Dizziness, diarrhea, headache, and nasopharyngitis were more common in MS patients receiving active treatment. More patients in the 30 mg/10 mg treatment group completed the trial than in the other two groups.

“Results from this study reproduce the strong efficacy of earlier trials,” Wynn said, while improving safety and tolerability.

“Despite the relatively small sample size of this study’s MS subpopulation,” Wynn said, the high-dose dextromethorphan combined with low-dose quinidine “was found to be significantly superior to placebo for decreasing PBA episode rate.”

He noted that further studies are warranted to evaluate the treatments effects on pain in MS.

“Having a drug that is tolerable to patients is as important as efficacy,” said Corey Ford, MD, of the University of New Mexico Health Sciences Center in Albuquerque, and past-president of the CMSC. “Improving tolerability is likely to increase the treatment’s usefulness to patients.”

A low-quinidine dose formulation of Zenvia is currently under consideration by the FDA for approval.

The study was supported by Avanir Pharmaceuticals.

Wynn made no other disclosures.

WASHINGTON — Several members of the FDA advisory committee that endorsed drospirenone-containing birth control pills had ties to Bayer, the company that makes the two most popular drospirenone-containing drugs, Yaz and Yasmin, according to a media report.

The panelists all participated in a Dec. 8 joint meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, which voted 15-11 that the benefits of drospirenone-containing birth control pills outweigh the risk of venous thromboembolism.

All members reported their industry ties to the FDA, which determined the conflicts didn’t preclude the members from participating in the meeting. The agency didn’t issue waivers for those members that would allow them to participate despite known biases, or make the disclosures public in any way, an investigation by BMJ and the Washington Monthly revealed.

The December meeting was held to address growing concerns about drospirenone-containing oral contraceptives — such as Yaz and Yasmin — and their link to increased risk for blood clots. There are currently multiple lawsuits pending over injuries and deaths related to drospirenone/ethinyl estradiol tablets (Yasmin and Yaz) and generic versions of the pills.

The panel’s acting chairwoman, Julia Johnson, MD, professor of obstetrics and gynecology at the University of Massachusetts Medical School, received money from Bayer for work she did for the company prior to 2009, which she acknowledged on a page on her university’s website. She also conducted four clinical trials for Berlex (which was acquired by Bayer), including one involving drospirenone.

The Project on Government Oversight (POGO) reported that the drospirenone study was not for birth control pills (it was for hormone replacement therapy) and that Johnson told POGO she has no bias for Bayer or Berlex products.

Another panelist who reported being a paid consultant to Bayer Schering received between $5,000 and $10,000 from the company in 2010 and attended two Bayer meetings that year; another conducted studies funded by Barr, which has a licensing agreement with Bayer to produce generic versions of Yaz; and still another received research funding from Bayer-Berlex and Duramed, which also has a licensing agreement for generic Yaz as well as Yasmin.

The relationships were disclosed in confidential documents reviewed by the FDA, and those four panelists were determined not to have conflicts of interest and thus were allowed to participate in the meeting. All four voted in favor of drospirenone-containing oral contraceptives.

However, several days before the meeting, it was announced that another panelist, Sidney Wolfe, MD, director of health research at consumer advocacy group Public Citizen, would not be allowed to participate because of a conflict of interest. Wolfe is an author of the consumer guide “Worst Pills/Best Pills” that warns readers to avoid drospirenone-containing products “due to the increased risks of blood clots.”

According to a Karen Riley, a spokeswoman for the FDA, Wolfe did not disclose that information to the FDA, and after the agency determined he had a conflict, they removed him from the committee but later gave him the option to serve as a nonvoting member, which he did.

“We think the reasoning that the FDA used to disqualify him from being a voting member was not logical and would lead to excluding anyone who had formed a scientific opinion about whether a particular drug should be or should not be approved for marketing, given the risk/benefit profile,” Michael Carome, MD, of Public Citizen, told MedPage Today.

Carome said it is a “great frustration” that Wolfe was banned from serving on the committee for a supposed “intellectual conflict” but other panelists were allowed to serve, even though they appeared to have financial conflicts of interest.

But Riley said the other panelists did not have conflicts of interest that would have precluded them from serving on the committee at the Dec. 8 meeting.

She pointed MedPage Today toward FDA’s policy on reviewing potential advisory committee members’ conflicts of interest which states that financial conflicts of interest are only grounds for disqualification from participating in a meeting if they are ongoing, or occurred within the past 12 months.

The same goes for “appearance” conflicts of interest, which are when the panelist doesn’t stand to gain financially from an FDA decision on the drug in question but there’s another reason that the panelist might appear to be biased.

“Since we didn’t issue waivers, we obviously didn’t identify an appearance issue,” Riley said in an email.

Carome said the members’ ties with Bayer should have been disclosed publicly, and POGO has asked the FDA to post committee members’ financial disclosure forms on a public website.

The conflicts of interest aren’t the only controversy that surrounded the Yasmin and Yaz meeting. Days before the meeting, court documents were unsealed in which former FDA commissioner David Kessler, MD, accused Bayer of hiding data on the blood clot risks associated with Yaz and Yasmin and engaging in “extensive” off-label promotion in order to increase sales.

The FDA advisory committee members were not shown those documents, however, because the date to submit materials for the committee’s review had passed, according to the FDA.

BOSTON — Long-term treatment with raltegravir (Isentress), an HIV-1 integrase inhibitor, appeared to improve outcomes for HIV-infected patients compared with treatment based on efavirenz (Sustiva), researchers said here.

Edwin DeJesus, MD, of the Orlando Immunology Center in Florida, and colleagues reported 192 week results from the phase III, STARTMRK study, which evaluated raltegravir-based therapy versus efavirenz-based therapy in treatment-naive patients.

The primary goal of STARTMRK was non-inferiority and, after 192 weeks of therapy, 76.2% of patients on raltegravir-based therapy had successfully suppressed HIV to undetectable levels, using the 50 copies/mL assay, versus 67% of patients on efavirenz-based therapy, he said.

The researchers randomized 281 individuals (RAL group) with HIV infection to receive raltegravir and 282 patients (EFV group) to treatment; both groups were also treated with tenofovir/emtricitabine (Truvada). The doses were 400 mg of raltegravir twice a day or 600 mg of efavirenz once a day.

About 80% of the cohort was men and the average patient age was 37 years at the start of the trial. About 41% of the patients in the study were white, 21.4% were Hispanic, 12.8% were Asian and 11.7% were black. The patients in the trial were naïve to antiretroviral therapy at enrollment.

According to the results, the percentage of patients with HIV RNA copies of <50 copies/mL at specified time points were: 48 weeks: 86.1 for the RAL group versus 81.9 for the EFV group for a difference of 4.2 (95% CI -1.9-10.3, P<0.01 for non-inferiority) 96 weeks: 81.1 for the RAL group versus 78.7 for the EFV group for a difference of 2.4 (95% CI -4.3-9, P<0.01 for non-inferiority) 156 weeks: 75.4 for the RAL group versus 68.8 for the EFV group for a difference of 6.6 (95% CI -0.8-14, P<0.01 for non-inferiority) 192 weeks: 76.2 for the RAL group versus 67 for the EFV group for a difference of 9 (95% CI 1.6=16.4, P<0.01 for non-inferiority)

In addition, the change from baseline in CD4 cell count (cells/mm2) was as follows: 48 weeks: 189.1 for RAL group versus 163.3 for EFV group for a difference of 25.8 (95% CI 4.4-47.2) 96 weeks: 240 for RAL group versus 224.8 for EFV group for a difference of 15.2 (95% CI -12.2-42.6) 156 weeks: 331.1 for RAL group versus 295.4 for EFV group for a difference of 35.9 (95% CI 3.4-68.3) 192 weeks: 360.7 for RAL group versus 300.9 for EFV group for a difference of 59.8 (95% CI 24.1-95.4)

DeJesus also noted that 50.2% of the patients on raltegravir reported adverse events during the four years of the trial compared with 80.1% of the patients on efavirenz (P<0.0001). However, there was no statistical difference between the 5% of raltegravir patients who discontinued treatment due to clinical adverse events and the 8.2% of those on efavirenz who left treatment due to adverse events.

“This study remains blinded and will continue for five years,” DeJesus told MedPage Today. “I am not aware of an HIV study that has continued to remain blinded for four years.”

“These results are very good,” commented Carlos Del Rio, MD, from Emory University in Atlanta, who moderated the IDSA poster session. “It is unfortunate that raltegravir is dosed twice daily. If this had been a once-daily drug, these results would be awesome.”

Del Rio told MedPage Today that clinicians often tire of looking at 48 week date for patients who will be on treatment for a lifetime. “It’s really nice to have this 192-week data. Both regimens are really very good but you want to see what happens long term.”

DeJesus disclosed relationships, financial and otherwise, with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman LaRoche, Achillion, Avexa, and Taimed.

Study co-authors disclosed relationships with multiple companies including Merck, Roche, Pfizer, Monogram BioSciences, and Gilead Sciences.

Del Rio had no disclosures.

BERLIN, Jan. 10 — Sugar-free gum, if chewed often enough, can lead to not only chronic diarrhea and functional bowel problems but also substantial unintended weight loss, researchers here warned.

Patients who popped 16 to 20 sticks of sorbitol-sweetened gum daily lost about 20% of their usual body weight, reported Juergen Bauditz, M.D., of the University of Berlin here, and colleagues in a case report in the Jan. 12 issue of BMJ.

Sorbitol, one of the most commonly used artificial sweeteners in chewing gum and candy as well as liquid medications, is poorly absorbed in the intestines, giving it the qualities of an osmotic laxative at higher doses (20 to 50 g).

Only a minority of people who chew sugar-free gum develop diarrhea or substantial unintended weight loss, Dr. Bauditz and colleagues noted. But when investigating unexplained weight loss, physicians should include a detailed dietary history of foods containing sorbitol, the German team concluded.

Even in relatively small doses of 5 to 20 g, sorbitol causes dose-dependent symptoms such as gas, bloating, and abdominal cramps. One stick of gum contains about 1.25 g.

However, many patients fail to recognize the link to their GI symptoms, Dr. Bauditz and colleagues said.

“As possible side effects are usually found only within the small print on foods containing sorbitol,” they wrote, “consumers may be unaware of its laxative effects.”

Even severe cases can go unrecognized, Dr. Bauditz’s group found.

Both cases they reported had extensive investigations for prolonged diarrhea and GI problems before a detailed examination of the patients’ eating habits led to a final diagnosis of excess sorbitol intake.

One patient, a 21-year-old woman underwent laboratory tests, colonoscopy, gastroscopy with deep duodenal biopsy, abdominal ultrasound, and CT following eight months of diarrhea and diffuse abdominal pain.

By the time she reached Dr. Bauditz’s department, she had lost about 24 pounds (11 kg) and had a body mass index of only 16.6 kg/m2. Laboratory analysis showed hypoalbuminemia from malabsorption.

She was initially suspected to have infectious colitis, but tests turned up normal.

Stool collection, though, raised suspicion that the patient was using an osmotic purgative, the researchers said.

They questioned her further and found that she typically consumed 18 to 20 g of sorbitol from sugar-free gum.

The other patient, a 46-year-old man, was admitted to the hospital after extensive diagnostic procedures failed to find a reason for persistent diarrhea and weight loss of nearly 50 pounds (22 kg) over about a year.

The researchers took a thorough history including detailed eating habits and again found a daily intake of about 30 g of sorbitol from about 20 sticks of sugar-free gum and up to 200 g of other artificially sweetened foods.

Stool electrolyte evaluation confirmed an abnormally high osmotic gap suggestive of sorbitol-induced osmotic diarrhea.

Simply eliminating sorbitol intake resolved the symptoms for both patients and they began to regain weight.

The authors reported no conflicts of interest.

Primary source: BMJ

Source reference:

Bauditz J, et al “Severe weight loss caused by chewing gum” BMJ 2008; 336: 96-7.

Canadian health officials are continuing to investigate a spike in anaphylaxis associated with one batch of the country’s H1N1 vaccine, made by GlaxoSmithKline.

Overall, the rate of anaphylaxis associated with the 15 million doses of the vaccine that have been shipped so far is 0.32 per 100,000 doses given, a Canadian health official told reporters late last week.

But six cases are associated with lot A80CA007A, which contained 172,000 doses of the adjuvanted Arepanrix vaccine, according to David Butler-Jones, MD, Canada’s chief public health officer.

All but about 15,000 doses of the lot had been used, so that the anaphylaxis rate was about four per 100,000 — markedly higher than the overall rate, Butler-Jones said.

All six patients recovered fully.

The spike in cases may be a result of chance, but the remaining doses are not being given while the investigators look into the issue.

Butler-Jones said there were no obvious glitches in the manufacturing process, but what investigators are “looking at is whether or not there was something else, whether it was something to do with when it was shipped.”

The issue “gives us cause to wonder whether there’s something wrong, or it may just be the odds,” he said. He added that the reactions do not appear to be related to the adjuvant used in the vaccine.

Since the vaccine program has been under way in Canada, Butler-Jones said, there have been 24 confirmed anaphylactic reactions, including one in which the patient died.

Butler-Jones said the man — reported to be in his 80s — met the criteria for an anaphylactic reaction, but it remains unclear whether that was the cause of death.

U.S. officials, meanwhile, said last week they have not seen anything unusual with their vaccines, with most reported reactions being local pain and redness. (See Bacterial Disease Linked to H1N1 Flu Worries CDC)

Anne Schuchat, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, said severe allergic reactions “are not showing up more commonly than we would expect.”

Worries that cramming multiple vaccinations into the first months of life slows brain development have no basis in fact, researchers said.

There was no evidence of neurodevelopmental delays or deficits associated with on-time vaccination in an intensively studied cohort of more than 1,000 children, according to Michael J. Smith, MD, and Charles R. Woods, MD, of the University of Louisville, in the June issue of Pediatrics.

“These data may reassure parents who are concerned that children receive too many vaccines too soon,” wrote Smith and Woods.

Although the link between certain childhood vaccines and autism has now been thoroughly debunked, the sheer number of vaccines that infants are supposed to receive is “another area of parental angst,” the researchers noted.

“Although the number of parents who completely refuse vaccines remains low, many families are requesting alternative immunization schedules that space out and delay receipt of the recommended childhood vaccines,” they wrote.

To determine whether these concerns may be valid, Smith and Woods analyzed data from the Vaccine Safety DataLink study, in which 1,047 children between the ages of 7 and 10 underwent 42 in-depth neuropsychological tests.

The study, which began in 1993, was originally conceived to examine whether thimerosal-containing vaccines were associated with later development of autism.

Children were enrolled from 1993 to 1997. At that time, the recommended vaccination schedule included two doses of hepatitis B vaccine, three for diphtheria-tetanus-pertussis, three for Haemophilus influenzae B, and two for polio during the first year.

Just under half the cohort (491) received the entire series in a timely way, defined as receiving each dose within 30 days of the recommended age.

There were some significant differences between the children who received timely vaccination and those who did not. Those with on-time vaccinations were slightly younger at the time of neuropsychological assessment (mean 9.2 versus 9.4 years), their mothers were better educated (56.8% with college degrees versus 46.8%), and they came from higher-income households (448% of poverty level versus 380%), all with P values of 0.001 or less.

Not one of the 42 tests showed better outcomes for those who did not have timely vaccine administration.

On some of the tests, timely vaccination was actually associated with improved performance compared with the untimely group, but only two of these associations remained significant in multivariate analysis, which included 16 potential confounders: speeded naming in the Developmental Neuropsychological Assessment test of speech and language, and the performance IQ subscale in the Wechsler Intelligence Scale for Children.

Smith and Woods also conducted a secondary analysis involving 310 children in the cohort whose vaccinations came closest to the recommended schedule and 112 with the least timely vaccinations.

The “most timely” group had received a mean of 11.2 doses through seven months of age, compared with a mean of 4.2 in the “least timely” group.

Multivariate analysis of these subgroups showed no differences in outcomes on any of the 42 tests.

The unadjusted univariate results indicated better performance in the most timely group on 15 tests; children with the least timely immunizations didn’t outperform the most timely group on any measure.

“The lack of any statistically significant results that favored delayed receipt of vaccines in the first year of life sends a clear public health message that should be comforting to many parents with vaccine safety concerns: Children can receive their immunizations on time and expect to have the same neurodevelopmental outcomes as children with any other pattern of vaccine receipt,” Smith and Woods concluded.

Limitations to the study included lack of a significant number of children receiving no vaccinations, and the enrollment period in the mid-1990s when the recommended vaccination schedule was different from today’s.

Also, children in the cohort may not be fully representative of the population at large, the researchers noted.

No external funding for the analysis was reported. The Vaccine Safety DataLink was supported by the CDC.

Smith and Woods are or have been unfunded subinvestigators for cross-coverage purposes on vaccine clinical trials for which their colleagues receive funding from Wyeth, Sanofi Pasteur, GlaxoSmithKline, MedImmune, and Novartis.

Woods has received honoraria for speaking engagements from Merck, Sanofi Pasteur, Pfizer, and MedImmune and has received research funding from Wyeth and Sanofi Pasteur.

Older women who are overweight or obese and lose more than 15 percent of their body weight could significantly boost their levels of vitamin D, new research suggests.

The study, conducted by researchers at Fred Hutchinson Cancer Research Center, also indicates that the surge in vitamin D could help scientists explore new avenues for the prevention of chronic diseases such as cancer and diabetes.

“Since vitamin D is generally lower in persons with obesity, it is possible that low vitamin D could account, in part, for the link between obesity and diseases such as cancer, heart disease and diabetes,” study author Caitlin Mason, a postdoctoral research fellow, said in a Hutchinson news release.

Vitamin D is fat-soluble nutrient that plays many important roles in the body, including promoting calcium absorption, reducing inflammation and influencing cell health and the immune system. It’s found in certain foods, such as fatty fish, and produced naturally in the body through exposure to sunlight.

The study, published in the May 25 online issue of the American Journal of Clinical Nutrition, assigned 439 overweight or obese postmenopausal women to one of four regimens: exercise only, diet only, exercise plus diet and no intervention.

Although women who lost up to 10 percent of their body weight (10 to 20 pounds) through diet and exercise saw modest increases in vitamin D, those levels were roughly three times higher in women who dropped more than 15 percent of their body weight, regardless of what they ate.

“We were surprised at the effect of weight loss greater than 15 percent on blood vitamin D levels,” study senior author Dr. Anne McTiernan, director of the Hutchinson Center’s Prevention Center, said in the news release. “It appears that the relationship between weight loss and blood vitamin D is not linear but goes up dramatically with more weight loss.”

McTiernan concluded the findings suggest the greater the weight loss, the more meaningful the surge in vitamin D levels.

The researchers noted, however, the degree to which vitamin D is available to the body during and after weight loss remains unclear. They also cautioned that more targeted research is needed to understand any link between vitamin D deficiency and chronic disease.

More information

The National Institutes of Health offers more information on the functions and sources of vitamin D.