Drora Fraser

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet

BACKGROUND Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. METHODS In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. RESULTS The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). CONCLUSIONS Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)

Reduction of Nasopharyngeal Carriage of Streptococcus pneumoniae after Administration of a 9-Valent Pneumococcal Conjugate Vaccine to Toddlers Attending Day Care Centers

A double-blind, randomized study involving 264 toddlers attending day care centers was conducted to document the effect of a 9-valent pneumococcal conjugate vaccine on the carriage rate of pneumococci. Of 3750 cultures done on nasopharyngeal samples obtained from subjects during a 2-year follow-up period after vaccination, 65% were positive for Streptococcus pneumoniae. In all age windows, the rate of carriage of vaccine-type pneumococci was lower among subjects who received the pneumococcal vaccine than among control subjects, because the acquisition rate was lower in the former group. The effect was most pronounced among subjects aged < or =36 months. The sample size enabled us to study protection against carriage of S. pneumoniae serotypes 6B, 9V, 14, 19F, and 23F; significant protection against all serotypes except 19F was seen in the pneumococcal-vaccine group. The rate of carriage of serotype 6A (not included in the vaccine) was also reduced significantly, but the rate of carriage of serotype 19A (not included in the vaccine) was not. The rate of carriage of non-vaccine-type pneumococci (excluding serotype 6A) was higher in the pneumococcal-vaccine group than in the control group.

Acquisition, Carriage, and Transmission of Pneumococci with Decreased Antibiotic Susceptibility in Young Children Attending a Day Care Facility in Southern Israel

The prevalence and transmission of antimicrobial drug-resistant pneumococci was studied in 48 children attending a day care facility in southern Israel. Nasopharyngeal cultures were obtained every 2 weeks for 10 months, and antibiotic susceptibility of isolates was determined by disk diffusion and E-test. Relatedness of isolates was investigated by capsular typing, ribotyping, and arbitrarily primed polymerase chain reaction. Pneumococci were recovered during 362 (63%) of 573 fortnights, and 219 (60%) of these isolates showed decreased susceptibility to at least one drug; 154 (43%) were intermediately susceptible to penicillin and 51 (14%) were multiresistant. Combining the different typing methods showed that a limited number of clones circulated in the facility. Clones exhibiting decreased antibiotic susceptibility (especially 23F, intermediately susceptible to penicillin and resistant to trimethoprim-sulfamethoxazole, and multiresistant 6B) were more frequently isolated and persisted longer than did fully susceptible clones. By multivariate analysis, carriage of organisms with decreased antibiotic susceptibility was associated with young age, female sex, winter season, and exposure to antimicrobial drugs during the previous month.

Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers

Background. In the developed societies, day-care centers (DCCs) play an important role in the spread of antibiotic-resistant pneumococci both within the facility and from the facility to the community. This study was conducted to determine the effect of a nonavalent pneumococcal conjugate vaccine (PCV-9) on the carriage of antibiotic-resistant pneumococci in the DCC. Subjects and methods. Healthy DCC attendees ages 12 to 35 months were randomized to receive either PCV-9 or a control vaccine (conjugate meningococcus C vaccine) in a double blinded manner. Nasopharyngeal Streptococcus pneumoniae cultures were obtained from each subject before vaccination, monthly during the first year of follow-up and every 2 to 3 months during the second year of follow-up. For each isolate the serotype and antibiotic susceptibility were determined Results. A total of 132 and 130 evaluable toddlers received either PCV-9 or the control vaccine, respectively. In total 3748 cultures were obtained, of which 2450 (65%) were positive for S. pneumoniae. The resistance rates to penicillin, trimethoprim-sulfamethoxazole and erythromycin were 36, 35 and 16%, respectively. Resistance rates to ≥1 and ≥3 antibiotic categories were 52 and 9%, respectively. Antibiotic resistance was found mainly in the 5 serotypes included in the pneumococcal conjugate vaccines (6B, 9V, 14, 19F and 23F) and in 2 related serotypes (6A and 19A). In the vaccinated group a clear and significant reduction of the carriage rate of the serotypes included in the vaccine and the related serotype 6A as well as an increase in the carriage rate of the serotypes not included in the vaccine were observed. In parallel a significant decrease in carriage rate of antibiotic-resistant pneumococci was observed. The reduction of carriage of antibiotic-resistant pneumococci was seen in all age windows but was greater in the age window <36 months. Conclusions. The carriage rate of antibiotic-resistant S. pneumoniae, including multiply resistant S. pneumoniae, in DCC attendees is high. Pneumococcal conjugate vaccines seem to be an important tool for reducing the carriage rate of antibiotic-resistant pneumonia in DCCs.

Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees.

Background. Incidence and severity of respiratory infections are increased in day-care center attendees. Streptococcus pneumoniae is an important contributor to these infections. Objective. To examine whether the use of a pneumococcal conjugate vaccine could reduce the occurrence of respiratory infections and the ensuing antibiotic drug use in the day care. Method. In this double blind, randomized, controlled study performed in 8 day-care centers located in Beer-Sheva, Israel, 264 toddlers ages 12 to 35 months at enrollment were randomized to receive either a 9-valent conjugate pneumococcal vaccine (conjugated to CRM197) or a control vaccine [conjugate meningococcus C vaccine (conjugated to CRM197)] and were followed for an average of 22 months. The main outcome measures were respiratory morbidity and antibiotic use. Results. An overall reduction of 7% in child months with ≥1 reported illness episodes was observed among vaccinees (P = 0.008), and 85% of all episodes were related to the respiratory tract. Reductions of 15, 16 and 17% were observed in upper respiratory infections, lower respiratory problems and otitis media, respectively. An overall reduction of 17% in antibiotic days was observed [10% for upper respiratory infections, 20% for otitis and 47% for lower respiratory problems (P ≤ 0.005 for each entity)]. The reduction in episodes and antibiotic use was greater for those <36 months of age than for the older children. Conclusion. The reduction of respiratory problems, including those not traditionally considered of pneumococcal origin and the ensuing lowered antibiotic use in day-care center attendees by pneumococcal conjugate vaccination suggest a broader benefit from the vaccine than preventing invasive disease only.

Serum Serotype-Specific Pneumococcal Anticapsular Immunoglobulin G Concentrations after Immunization with a 9-Valent Conjugate Pneumococcal Vaccine Correlate with Nasopharyngeal Acquisition of Pneumococcus

BACKGROUND Immunization with pneumococcal conjugate vaccines (PCVs) reduces nasopharyngeal colonization by Streptococcus pneumoniae. We attempted to correlate postvaccination serum serotype-specific pneumococcal anticapsular immunoglobulin (Ig) G concentrations with new acquisitions of vaccine-type (VT) serotypes and the VT-related serotype 6A. METHODS A total of 132 day care center attendees aged 12-35 months received a 9-valent PCV (PnCRM9) and were followed for 2 years for new nasopharyngeal acquisitions of S. pneumoniae. A total of 132 control subjects received a meningococcus type C conjugate vaccine. Serum serotype-specific pneumococcal anticapsular IgG concentrations were determined at 1 month after complete immunization. RESULTS A logistic regression model of the probability of having a new acquisition of S. pneumoniae (for serotypes 9V, 14, 19F, and 23F) as a function of the IgG concentration showed a negative coefficient, indicating that higher IgG concentrations led to a decreasing probability of having a new acquisition, and achieved statistical significance for serotypes 14 and 19F. Similarly, a new acquisition of serotype 6A was shown to be significantly inversely related to the anti-6B IgG concentration. An effect of the IgG concentration on duration of carriage was not demonstrated. CONCLUSION The magnitude of herd protection against S. pneumoniae provided by a PCV may depend on the magnitude of IgG concentrations.

Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.

Aim. We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9;n = 132), or a control vaccine (meningococcus C vaccine;n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. Results. Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively;P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively;P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively;P < 0.001) and their younger siblings (19% vs. 13%, respectively;P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to ≥1, ≥2 and ≥3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. Conclusion. The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.

Glycemic Effects of Moderate Alcohol Intake Among Patients With Type 2 Diabetes A multicenter, randomized, clinical intervention trial

OBJECTIVE—In a randomized controlled trial, we assessed the effect of daily moderate alcohol intake on glycemic control in the fasting and postprandial states in patients with type 2 diabetes who previously had abstained from alcohol. RESEARCH DESIGN AND METHODS—We randomly assigned 109 patients (41–74 years old) with established type 2 diabetes who abstained from alcohol to receive 150 ml wine (13 g alcohol) or nonalcoholic diet beer (control) each day during a 3-month multicenter trial. The beverages were consumed during dinner. Diet and alcohol consumption were monitored. RESULTS—During the intervention, 17% of participants (12% from the alcohol group) dropped out, leaving 91 who completed the trial. Within the alcohol group, fasting plasma glucose (FPG) decreased from 139.6 ± 41 to 118.0 ± 32.5 mg/dl after 3 months compared with 136.7 ± 15.4 to 138.6 ± 27.8 mg/dl in the control subjects (Pv = 0.015). However, alcohol consumption had no effect on 2-h postprandial glucose levels (difference of 18.5 mg/dl in the control group vs. 17.7 mg/dl in the alcohol group, Pv = 0.97). Patients in the alcohol group with higher baseline A1C levels had greater reductions in FPG (age-adjusted correlation −0.57, Pv < 0.001). No significant changes were observed in the levels of bilirubin, alkaline phosphatase, alanine aminotransferase, or aspartate aminotransferase, and no notable adverse effects were reported. Participants in the alcohol group reported an improvement in the ability to fall asleep (Pv < 0.001). CONCLUSIONS—Among patients with type 2 diabetes who had previously abstained from alcohol, initiation of moderate daily alcohol consumption reduced FPG but not postprandial glucose. Patients with higher A1C may benefit more from the favorable glycemic effect of alcohol. Further intervention studies are needed to confirm the long-term effect of moderate alcohol intake.

A Decade (1989–1998) of Pediatric Invasive Pneumococcal Disease in 2 Populations Residing in 1 Geographic Location: Implications for Vaccine Choice

During 1 decade (1989-1998), data on invasive pneumococcal disease were collected prospectively to assess the burden of disease among Jewish and Bedouin children in southern Israel and the potential reduction in illness that can be achieved by using conjugate vaccines. Data on 513 children <15 years old with bacteriologically proven invasive pneumococcal disease were obtained. Among Jewish and Bedouin children <5 years old, incidence rates were 45 and 139 cases per 100,000 child-years of observation, respectively. Jewish and Bedouin children differed in clinical manifestations, seasonal patterns of disease, serotype distribution, and antibiotic susceptibility rates. The potential coverage by 7-, 9-, and 11-valent conjugate vaccines is 41%, 67%, and 71%, respectively, for Jewish children and 22%, 63%, and 65%, respectively, for Bedouin children. The 9- and 11-valent pneumococcal conjugate vaccines have the potential to substantially decrease invasive pneumococcal disease in southern Israel.

Marked Differences in Pneumococcal Carriage and Resistance Patterns between Day Care Centers Located within a Small Area

Carriage rates of Streptococcus pneumoniae and their antibiotic resistance, capsular types, and genetic patterns were studied among 264 children aged 12-35 months attending 8 day care centers located within a 2.5-mile radius in the same city. Nasopharyngeal cultures were obtained within a 2-month interval from all 264 children. Significant differences in each of the studied characteristics were found between day care centers, and each day care center had a unique pattern of the carried pneumococci. Our findings show that day care centers are independent microenvironments and emphasize their role in the transmission and augmentation of antibiotic-resistant S. pneumoniae in the community.