An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia

The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.     

Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis

Background

Limited data exist on optimal empiric oral antibiotic treatment for outpatients with cellulitis in areas with a high prevalence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methods

We conducted a 3-year retrospective cohort study of outpatients with cellulitis empirically treated at a teaching clinic of a tertiary-care medical center in Hawaii. Patients who received more than 1 oral antibiotic, were hospitalized, or had no follow-up information were excluded. Treatment success rates for empiric therapy were compared among commonly prescribed antibiotics in our clinic: cephalexin, trimethoprim-sulfamethoxazole, and clindamycin. Risk factors for treatment failure were evaluated using multivariate logistic regression analysis.

Results

Of 544 patients with cellulitis, 405 met the inclusion criteria. The overall treatment success rate of trimethoprim-sulfamethoxazole was significantly higher than the rate of cephalexin (91% vs 74%; P < .001), whereas clindamycin success rates were higher than those of cephalexin in patients who had subsequently culture-confirmed MRSA infections (P = .01), had moderately severe cellulitis (P = .03), and were obese (P = .04). Methicillin-resistant S. aureus was recovered in 72 of 117 positive culture specimens (62%). Compliance and adverse drug reaction rates were not significantly different among patients who received these 3 antibiotics. Factors associated with treatment failure included therapy with an antibiotic that was not active against community-associated MRSA (adjusted odds ratio 4.22; 95% confidence interval, 2.25-7.92; P < .001) and severity of cellulitis (adjusted odds ratio 3.74; 95% confidence interval, 2.06-6.79; P < .001).

Conclusion

Antibiotics with activity against community-associated MRSA, such as trimethoprim-sulfamethoxazole and clindamycin, are preferred empiric therapy for outpatients with cellulitis in the community-associated MRSA-prevalent setting.     

Toxicity and mutagenicity of a mixture of 25 chemicals found in contaminated groundwater

A defined mixture of 25 chemicals that are often found in contaminated groundwater was prepared as an aqueous solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effects in bone marrow cells of rats and mice. The bacterial mutation and prophage induction tests were negative. Exposure to the mixture in drinking water for two weeks resulted in a concentration-related decrease in water consumption in male and female rats and mice. Concentration-related decreases in weight gain were observed in male and female mice; in rats, only the high-dose groups showed decreased weight gains. A small but significant increase in sister chromatid exchanges was seen in male mice and a similar weak effect on micronucleated polychromatic erythrocytes (PCE) in the bone marrow of males and females. Also in bone marrow of male and female mice, an increase in mitotic index and a decrease in average cell generation time was observed. The %PCE in bone marrow was decreased in female mice only, while the %PCE in peripheral blood was increased in both sexes. In rats, the only effects observed in the cytogenetic studies were increased PCE frequencies in the peripheral blood of males and in the bone marrow of males and females. These results indicate that the 25-chemical mixture studied is not genotoxic in bacteria and that a concentration-dependent effect on its palatability to rodents leads to reduced water consumption, food consumption and weight gain. Although the bone marrow effects may be associated with disruptions of normal erythropoiesis that, in turn, alter the cytogenetic end-points reported, elevations of SCE and MN-PCE in mice suggest the 25-chemical mixture, under the conditions of administration, leads to cytogenetic damage in the bone marrow. Such damage may indicate a potential health hazard.     

Thyrotoxic periodic paralysis in a Polynesian male following highly active antiretroviral therapy for HIV infection

Hyperthyroidism has been described after highly active antiretroviral therapy for AIDS and has been attributed to late onset immune reconstitution. The team reports a young Polynesian man with AIDS who responded to highly active antiretroviraltherapy. However, 15 months after initiation of antiretroviral therapy, he was hospitalized for hypokalemic thyrotoxic periodic paralysis, an unusual manifestation of hyperthyroidism which typically occurs in young Asian males.     

Culturally sensitive strategies designed to target the silent epidemic of hepatitis B in a Filipino community

Hepatitis B is frequent in the Philippines. A high rate of immigration to the United States has brought many Filipinos with infections who are asymptomatic yet will go on to develop liver cancer and cirrhosis unless diagnose and evaluated. Interventions are necessary to educate this ethnic community, identify those infected, and offer therapy. In an effort to reach this high risk population in Hawai'i an intervention program was designed to address the silent epidemic of hepatitis. Ethnic barriers were crossed through involvement of trusted, key stakeholders and individuals within the Filipino health care and church communities, along with groups that had joint missions to address viral hepatitis. After extensive planning and meetings with faith-based organizations and health care providers in the Filipino community, it was decided to hold a community health fair in the Filipino community to provide culturally appropriate health information and services. More than 500 individuals attended the health fair; 167 participated in a survey and were tested for hepatitis B. Significant knowledge gaps were found in relation to risk factors, prevention strategies, and transmission. Five individuals tested positive; all were immigrants and did not know of their disease. The objective to educate people and test them for hepatitis was successful through utilizing ethnic community leaders, religious organizations, health care professionals, and a collaborative health fair.     

InVivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs) targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX), monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT) were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.     

Septic bursitis in the prepatellar and olecranon bursae: an analysis of 25 cases

Five cases of septic prepatellar and 20 cases of septic olecranon bursitis are reported. All were men, with a mean age of 47 years. Seventeen had a history of recent trauma to the affected limb or sustained pressure on knees or elbows, or both, required by certain occupations. Septic bursitis was not associated with septic arthritis and could be easily distinguished from it by the characteristic bursal swelling and joint examination. Septic bursitis was misdiagnosed as nonseptic bursitis in eight cases despite characterstic bursal fluid leukocytosis (greater than 1000 cells/mm3) and recovery of bacteria on culture. Staphylococcus aureus was identified in 22 cases; 76% were resistant to penicillin. Intravenous antibiotics and bursal fluid drainage were uniformly succesful. Oral antibiotic ttherapy was also successful unless the infection was extensive or there was underlying bursal disease. Early recognition, prompt therapy, and preventive measures are necessary to reduce the morbidity of septic bursitis.