Randomized controlled trial to assess the effectiveness of a primary health care liaison worker in promoting shared care for opiate users

BACKGROUND: Recent national guidelines emphasize the requirement for all general practitioners to manage drug users within a shared care scheme and suggest that a primary health care liaison worker (PHCLW) may facilitate these arrangements. We undertook a group-randomized, randomized controlled trial to determine the effectiveness of a PHCLW in promoting shared care. METHODS: Primary health care teams in Stockport Health Authority, North West England, were randomly allocated to either an intervention arm, who were offered the services of a PHCLW, or to a control arm, who were offered standard support from the community drug team (CDT). The proportion of CDT clients with a history of regular opiate misuse who were in shared care 12 months after randomization was compared across study arms. RESULTS: Eighteen (24.0 per cent) of the 75 CDT clients in the intervention arm but none of the 80 CDT clients in the control arm were in shared care at 12 months (chi2 = 9.37, df = 1, p < 0.01; 95 per cent confidence interval 8.6-39.4 per cent). CONCLUSION: A PHCLW can significantly increase the number of CDT clients in shared care arrangements.     

Randomized controlled trial to evaluate effectiveness of exercise therapy (Takizawa Program) for frail elderly

Objective Although exercise therapy intervention for frail elderly people was not of great interest in the past, it has recently drawn attention as a method to prevent and improve conditions requiring care since the enforcement of the Long-Term Care Insurance Law and the revision of the long-term care insurance system. This randomized controlled trial was performed to evaluate the effects of exercise therapy using the Takizawa Program. Methods In this randomized controlled trial, we evaluated the effects of exercise therapy on the frail elderly, including those who need a high level of care, in terms of two factors: the range of motion and the functional independence measure. The subjects were 145 females admitted to special nursing homes for the elderly. They were stratified according to their care levels and randomly assigned to either the exercise therapy intervention group or the control group. Results The range of motion values in the flexions of both shoulders, the right knee extension, and the dorsal flexions of both ankles significantly increased only in the exercise therapy intervention group. The functional independence measure score did not improve in the exercise therapy intervention group. Conclusion Exercise therapy should be used for the frail elderly requiring a high level of care.     

Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of malaria vaccine PfCS102 to protect against challenge with P. falciparum

The aim of this Phase I/IIa double-blind controlled trial was to test the efficacy of the sporozoite-based malaria vaccine PfCS 282–383 (PfCS102) to protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized to receive twice 30 μg of PfCS102 formulated in Montanide ISA 720 or ISA 720 alone (control). Two weeks after 2nd immunization, volunteers were challenged using 5 infected mosquitoes. All vaccinees developed antibodies against PfCS102 versus none control. 8/8 vaccinees and 6/6 controls challenged developed malaria parasitaemia. The duration from infection to onset of patent parasitaemia was similar in both groups (214 h in vaccinees and 216 in controls). PfCS102 is safe and immunogenic but provides no protection against artificial challenge in its current formulation.     

Evaluation of an attenuated strain of Ehrlichia canis as a vaccine for canine monocytic ehrlichiosis

Canine monocytic ehrlichiosis is an important tick-borne disease worldwide. No commercial vaccine for the disease is currently available and tick control is the main preventive measure against the disease. The aim of this study was to evaluate the potential of a multi-passaged attenuated strain of Ehrlichia canis to serve as a vaccine for canine monocytic ehrlichiosis, and to assess the use of azithromycin in the treatment of acute ehrlichiosis. Twelve beagle dogs were divided into 3 groups of 4 dogs. Groups 1 and 2 were inoculated (vaccinated) with an attenuated strain of E. canis (#611A) twice or once, respectively. The third group consisted of naïve dogs which served as controls. All 3 groups were challenged with a wild virulent strain of E. canis by administering infected dog-blood intravenously. Transient thrombocytopenia was the only hematological abnormality observed following inoculation of dogs with the attenuated strain. Challenge with the virulent strain resulted in severe disease in all 4 control dogs while only 3 of 8 vaccinated dogs presented mild transient fever. Furthermore, the mean blood rickettsial load was significantly higher in the control group (27–92-folds higher during days 14–19 post challenge with the wild the strain) as compared to the vaccinated dogs. The use of azithromycin was assessed as a therapeutic agent for the acute disease. Four days treatment resulted in further deterioration of the clinical condition of the dogs. Molecular comparison of 4 genes known to express immunoreactive proteins and virulence factors (p30, gp19, VirB4 and VirB9) between the attenuated strain and the challenge wild strain revealed no genetic differences between the strains. The results of this study indicate that the attenuated E. canis strain may serve as an effective and secure future vaccine for canine ehrlichiosis.     

Double-blind randomized efficacy field trial of alum precipitated autoclaved Leishmania major vaccine mixed with BCG against canine visceral leishmaniasis in Meshkin-Shahr district, I.R. Iran

This study was designed to evaluate the efficacy of a single dose of aluminum hydroxide (alum) precipitated Leishmania major (Alum-ALM) vaccine plus BCG against canine visceral leishmaniasis. Three hundred and forty-seven healthy dogs with no anti-Leishmania antibodies were double-blind randomly injected intradermally with either 0.1ml of Alum-ALM (200 microg protein) mixed with BCG (182 dogs) or injected with 0.1ml of normal saline (165 dogs). The results of 16 months follow-up showed that the vaccine was safe and well-tolerated. Strong seroconversion using DAT and ELISA techniques at 16 months post-vaccination was considered as an indication of Leishmania infection. The incidence rate was 3.7% (6/162) in vaccinated group and 12.0% (17/141) in control group using DAT technique. The efficacy of the vaccine was calculated to be 69.3%.     

The serological response in dogs inoculated with canine distemper virus vaccine at the acupuncture point governing vessel-14: A randomized controlled trial

The improvement of immunity to vaccination has historically focused on manipulation of antigen presentation rather than the host. Immune modulation by stimulating specific acupuncture points along the Meridian System has been practiced in Traditional Chinese Medicine. The purpose of this study was to quantitatively determine whether acupoint vaccination, in which vaccine is administered at an acupuncture point in dogs, has the potential to enhance the immune response.A randomized controlled trial was conducted to compare the effectiveness of acupoint vaccination versus a conventional method, based on humoral immune response in dogs given Canine Distemper Vaccine (CDV). One hundred client-owned dogs were admitted to the study with following characteristics: (1) passed a routine physical exam, (2) aged between 1 and 10?years old, (3) had no history of chronic disease, and (4) were not on immunomodulating medications. Dogs were randomly assigned to either the Acupuncture group inoculated at the acupoint Governing Vessel (GV)-14, or to the Control group inoculated conventionally at a non-acupuncture site. Mean changes from Day0 to Day14 of the response to CDV vaccination, measured by serum neutralization (SN) titers with log-transformation for reducing outlier effects, were compared between groups. No significant difference was found between groups in age, weight, or sex (all p?>0.2). Both groups had significant increases of CDV SN titer post-vaccination (p?<?0.001). The mean increase in Acupuncture group (0.72; SD?=?0.79) was significantly greater than that of the Control group (0.36; SD?=?0.67); p?=?0.019. Inference on percentage of change in raw SN titer data further revealed that the effects in the Acupuncture group was significantly greater than the Control group (242% vs. 83%; p?=?0.02).This study demonstrated that Acupoint vaccination at GV-14 resulted in a significantly elevated humoral immune response to CDV vaccine compared to Controls, which suggests the potential of acupoint vaccination to enhance the immune response.     

Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response

A live oral cholera vaccine developed from a non-toxigenic Vibrio cholerae O1 El Tor strain VA1.3 was tested in a double-blind randomized placebo controlled study for safety and immunogenicity in 304 men aged between 16 and 50 years from Kolkata, India. A dose of 5 × 10⁹ CFU (n = 186) or a placebo (n = 116) containing the diluent buffer was administered. The vaccine did not elicit adverse events except in two vaccine recipients with mild diarrhoea and vomiting. None excreted the vaccine strain. Vibriocidal antibody response developed in 105/186 (57%) and 5/116 (4%) in vaccine and placebo recipients, respectively. In a subgroup, anti-CT antibody rose (≥2-folds) in 23/30 (77%) and 6/19 (32%) in vaccine and placebo recipients, respectively. These studies demonstrate that VA1.3 at a dose of 5 × 10⁹ is safe and immunogenic in adults from a cholera endemic region.     

Randomized controlled trial to determine the effectiveness of an interactive multimedia food safety education program for clients of the special supplemental nutrition program for women, infants, and children

BACKGROUND: Pregnant women and the very young are among those most susceptible to foodborne infections and at high risk of a severe outcome from foodborne infections. OBJECTIVE: To determine if interactive multimedia is a more effective method than pamphlets for delivering food safety education to Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) clients. DESIGN: A randomized controlled trial of WIC clients was conducted. Self-reported food safety practices were compared between pre- and postintervention questionnaires completed >or=2 months after the intervention. SUBJECTS/SETTING: Pregnant WIC clients or female caregivers (usually mothers) of WIC clients who were 18 years of age or older and able to speak and read English were recruited from an inner-city WIC clinic. INTERVENTION: Participants were randomized to receive food safety pamphlets or complete an interactive multimedia food safety education program on a computer kiosk. MAIN OUTCOME MEASURES: Change from pre- to postintervention food safety scores. STATISTICAL ANALYSES PERFORMED: A mean food safety score was determined for each participant for the pre- and postintervention questionnaires. The scores were used in a two-group repeated measures analysis of variance. RESULTS: Of the 394 participants, 255 (64.7%) completed the postintervention questionnaire. Satisfaction with the program was high especially among those with no education beyond high school. When considering a repeated measures analysis of variance model with the two fixed between-subject effects of group and age, a larger improvement in score in the interactive multimedia group than in the pamphlet group (P=0.005) was found, but the size of the group effect was small (partial eta(2)=0.033). Women aged 35 years or older in the interactive multimedia group had the largest increase in score. CONCLUSIONS: The interactive multimedia was well-accepted and resulted in improved self-reported food safety practices, suggesting that interactive multimedia is an effective option for food safety education in WIC clinics.     

Use of the state immunization information system to assess rotavirus vaccine effectiveness in Connecticut, 2006-2008

Immunization information systems (IIS) contain individual vaccination records and have potential use for evaluating post-licensure vaccine effectiveness (VE). A matched case-control study was performed by using the Connecticut state IIS to calculate rotavirus VE against hospitalization; results were compared with pre-licensure efficacy and with estimates previously obtained by traditional case-control methods using matched controls from medical sources and medical chart abstracted data. Case-patients (n = 54) were vaccine-eligible children with IIS entry and hospitalized for rotavirus gastroenteritis during July 2006-December 2008; each was matched to five control subjects (n = 270) who were randomly selected from IIS based on case-patient's birth date and town of residence. VE of at least one dose was 90.6%, comparable to the pre-licensure efficacy of 96% and to the unadjusted 83.5-90.7% estimates by using traditional case-control methods. IIS can be a convenient and potentially accurate tool for calculating VE.     

Randomized,double-blind,Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers

Development of a cytomegalovirus (CMV) vaccine is a priority. We evaluated a two component alphavirus replicon particle vaccine expressing CMV gB or a pp65/IE1 fusion protein, previously shown to induce robust antibody and cellular immune responses in mice, in a randomized, double-blind Phase 1 clinical trial in CMV seronegative subjects. Forty subjects received a lower dose (LD) or higher dose (HD) of vaccine or placebo by intramuscular or subcutaneous injection at Weeks 0, 8 and 24. The vaccine was well tolerated, with mild to moderate local reactogenicity, minimal systemic reactogenicity, and no clinically important changes in laboratory parameters. All vaccine recipients developed ex vivo, direct IFN-γ ELISPOT responses to CMV antigens (maximal mean spot-forming cells per 10⁶ PBMC in LD and HD groups of 348 and 504 for pp65, 83 and 113 for IE1, and 138 and 114 for gB), and neutralizing antibodies (maximal geometric mean titer 110 with LD and 218 with HD). Polyfunctional CD4⁺ and CD8⁺ T cell responses were detected by polychromatic flow cytometry. This alphavirus replicon particle vaccine was safe and induced neutralizing antibody and multifunctional T cell responses against three CMV antigens that are important targets for protective immunity.     

Randomized double-blind placebo controlled trial to evaluate the safety and immunogenicity of the live oral cholera vaccine strain CVD 103-HgR in Swiss adults

A randomized, double-blind, placebo controlled trial was conducted in 50 healthy Swiss adults to assess the safety and immunogenicity of the live oral attenuated cholera vaccine candidate strain Vibrio cholerae CVD 103-HgR (classical, Inaba). A single dose of 5 × 10⁸ viable CVD 103-HgR organisms, administered in a buffered liquid formulation, was well tolerated as compared with individuals who received an equivalent amount of heat-killed Escherichia coli K-12 placebo. Eighty-eight percent of subjects receiving CVD 103-HgR mounted a significant (>fourfold) rise in Inaba vibriocidal titre while 68% did so for the heterologous Ogawa serotype. The magnitude of the vibriocidal antibody response (as measured by peak geometric mean titre and by fold-rise in titre over baseline) was greater for the homologous Inaba serotype. Nineteen out of 25 volunteers (76%) responded with a significant (p < 0.05) rise in serum antitoxin levels. No vaccine who received the E. coli K-12 placebo mounted a significant rise in either vibriocidal or antitoxin antibody levels. These results corrobrate the safety and immunogenicity of CVD 103-HgR in healthy adult volunteers.     

One-week intramuscular or intradermal pre-exposure prophylaxis with human diploid cell vaccine or Vero cell rabies vaccine,followed by simulated post-exposure prophylaxis at one year: A phase III,open-label,randomized, controlled trial to assess immunogenicity and safety

Shorter rabies pre-exposure prophylaxis (PrEP) regimens may offer improved convenience and feasibility over classic 3-week regimens, for example in regions with poor access to vaccines or for travelers to rabies-endemic regions. In this multicenter, open-label, controlled trial, 570 healthy participants aged 2–64 years were randomized to receive: 1-week PrEP (vaccination days [D]0 and 7; Group 1) or classic 3-week PrEP regimen (D0, D7, and D21; Group 2) with one 1.0 mL intramuscular [IM] dose of human diploid cell culture rabies vaccine (HDCV) at each visit; 1-week PrEP with two 0.1 mL intradermal (ID) HDCV doses at each visit (Group 3); or 1-week PrEP with one 0.5 mL IM dose (Group 4) or two 0.1 mL ID doses (Group 5) of Vero cell rabies vaccine (PVRV) at each visit. Participants received simulated post-exposure prophylactic (PEP) vaccination (two IM or ID doses of HDCV or PVRV three days apart) one year later. Rabies virus neutralizing antibody titers and seroconversion (titers ≥ 0.5 IU/mL) rates were assessed 14 days and up to 1 year post-PrEP, and pre- and post-PEP. Safety was assessed throughout the study. Seroconversion rates were high 14 days post-last PrEP injection (ranging from 96.7 % to 97.2 % across groups 1, 3–5; 1-week PrEP) and reached 100 % in Group 2 (3-week PrEP). Non-inferiority of Group 1 versus Group 2 in terms of seroconversion rates 14 days post-last PrEP injection (primary objective) was not demonstrated. After simulated PEP, all groups showed rapid and robust immune responses, with all but one participant achieving seroconversion (titers ≥ 0.5 IU/mL). There were no safety concerns, and the tolerability profiles of the vaccines were similar across the groups.A 1-week, IM or ID PrEP regimen with HDCV or PVRV provided efficacious priming, enabling rapid robust anamnestic responses to simulated PEP 1 year later across age groups.ClinicalTrials.gov number: NCT03700242.WHO Universal Trial Number (UTN): U1111-1183-5743.     

Auricular acupuncture as an adjunct for pain management during first trimester abortion: a randomized,double-blinded,three arm trial

Objectives

To assess pain-management using auricular acupuncture as an adjunct to ibuprofen and paracervical block during first trimester uterine aspiration, and to assess auricular acupuncture's effect on anxiety.

Randomized,double-blind,placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 × 10⁹ CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24 h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.     

A multinational,randomized, placebo-controlled trial to assess the immunogenicity,safety, and tolerability of live attenuated influenza vaccine coadministered with oral poliovirus vaccine in healthy young children

Live attenuated influenza vaccine (LAIV) provides a useful tool to rapidly immunize populations in the developing world to prevent influenza outbreaks. In this noninferiority trial conducted in Asia and South America, where oral poliovirus vaccine (OPV) is still used, 2503 children aged 6 to <36 months with three polio immunizations were randomized to receive LAIV + OPV, placebo + OPV, or LAIV only. Immune responses in children receiving concomitant LAIV + OPV were noninferior to those observed in recipients of either vaccine alone. Response rates for different poliovirus types were similar in recipients of LAIV + OPV and placebo + OPV. Response rates to all influenza strains were similar in LAIV + OPV and LAIV-only recipients. Concomitant OPV and LAIV were safely administered to young children.     

A randomized and blinded field trial to assess the efficacy of an autogenous vaccine to prevent naturally occurring infectious bovine keratoconjunctivis (IBK) in beef calves

A randomized and blinded 2-arm parallel trial was conducted to assess the efficacy of an autogenous vaccine to prevent naturally occurring infectious bovine keratoconjunctivis (IBK) in beef calves. The trial was managed between May and November 2008 on university owned farms in Iowa and Wisconsin. The vaccine at Iowa contained Moraxella bovoculi (M. bovoculi) while the organism used in the Wisconsin herds vaccine was Branhemella ovis (B. ovis renamed M. ovis). Calves born between January and May 2008 without visible corneal lesions were randomized to receive an autogenous vaccine or placebo vaccine using a computer generated sequence. Two subcutaneous doses were administered 21–28 days apart. Allocation to treatment was concealed using bottles marked A or B. Staff were blind to the treatment allocation. The primary outcome was IBK cumulative incidence over the study period. The secondary outcome was weaning weight. Only the Iowa herd met the criteria for an “at-risk” herd i.e. >15% IBK in unvaccinated calves and M. bovoculi isolation from IBK cases. Analysis was “per-protocol”. The cumulative incidence of IBK was 47/105 in vaccinated calves and 49/109 in unvaccinated calves (unadjusted odds ratio = 0.99, 95% CI: 0.58–1.70). Weight at weaning did not differ between the vaccinated cohort 148 kg (SD: ±27) and unvaccinated cohort 146 kg (SD: ±26) (unadjusted β = 1.5 and 95% CI: −5.5 to 8.6). Results indicate that the autogenous vaccine was ineffective in this study population.     

Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age,a randomized controlled trial

Background

To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS).

Methods

Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS.

Findings

By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p < 0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p < 0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p < 0.001).

Interpretation

Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.     

A phase III randomized, controlled study to assess the immunogenicity and tolerability of DTPw-HBV-Hib, a liquid pentavalent vaccine in Indian infants

Immunogenicity and tolerability of two liquid pentavalent vaccines, Pentavac^® (new vaccine), and Easyfive^® (available in the market) was assessed in a multicentre study in India. In all, 484 infants aged 6-8 weeks were enrolled, and their blood samples were assessed prior to the first dose and one month after the third dose. A 100% seroprotection rate was achieved with both vaccines’ antigens, except pertussis for which the response was 95% and 96%, respectively, for the two vaccines. A diary-based recording of adverse events showed that the two most common events were pain at the injection site and restricted limb movements and were less frequent (p < 0.001) among the recipients of the new vaccine. The new vaccine meets all criteria of childhood vaccination. Its low reactogenicity and low cost are valid reasons to recommend this vaccine for general use.