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Summary: The present study tested if the accuracy of the VFA reading reproducibility is more affected by the statistical tool used or by the reader's level of expertise in 50 VFA from a population-based cohort, the OstéoLaus study. We found that uniform kappa and instruction reading with the ISCD/IOF VFA reading course both increased the accuracy of the reproducibility. Introduction: Vertebral fractures (VF) due to osteoporosis are under diagnosed. Screening osteoporosis in the general population allows improving management of fragility fracture. It consists to perform a dual X-ray absorptiometry and a spine X-ray to look at a VF. To reduce the dosage of radiation, prevalent or incident VF could be detected by DXA image. The aim of the present study was to test the reproducibility of vertebral fracture assessment (VFA) readings in a population-based cohort and to explore if the accuracy of the reproducibility is more affected by the statistical tool used or by the reader's level of expertise. Methods: We calculated the reproducibility of VFA reading by uniform and Cohen's kappa, comparing one expert and one non-expert, before and after an instructional on-line International Society of Clinical Densitometry (ISCD) /International Osteoporosis Foundation (IOF) course on VFA reading. We performed the analysis on 50 VFA from a population-based cohort, the OstéoLaus study. Results: Before the VFA reading course, reproducibility with Cohen's kappa was moderate to poor (0 to 0.520), good with the uniform kappa (0.796 to 0.958). After the course, both Cohen's kappa and uniform kappa statistically increased, ranging from 0.524 to 1.000. Conclusions: For female population-based cohort studies, we recommend using the uniform kappa and instructing a non-expert reader using the ISCD/IOF VFA reading course to correctly read and evaluate the reproducibility of the VFA reading. [ABSTRACT FROM AUTHOR]

Summary: Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. Introduction: The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. Methods: Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide ( N = 65) or quarterly intravenous IBN ( N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. Results: Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m, BMD L1-L4 0.741 ± 0.100 g/cm, and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline ( r = 0.04) with no correlation between the changes in BMD and TBS over 24 months. Conclusions: In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN. [ABSTRACT FROM AUTHOR]

Summary: We evaluated the effectiveness of supplementation with high dose of oral vitamin D3 to correct vitamin D insufficiency. We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients and that the patients who benefited more from supplementation were those with the lowest baseline levels. Introduction: Adherence with daily oral supplements of vitamin D3 is suboptimal. We evaluated the effectiveness of a single high dose of oral vitamin D3 (300,000 IU) to correct vitamin D insufficiency in a rheumatologic population. Methods: Over 1 month, 292 patients had levels of 25-OH vitamin D determined. Results were classified as: deficiency <10 ng/ml, insufficiency ≥10 to 30 ng/ml, and normal ≥30 ng/ml. We added a category using the IOM recommended cut-off of 20 ng/ml. Patients with deficient or normal levels were excluded, as well as patients already supplemented with vitamin D3. Selected patients (141) with vitamin D insufficiency (18.5 ng/ml (10.2-29.1) received a prescription for 300,000 IU of oral vitamin D3 and were asked to return after 3 (M3) and 6 months (M6). Patients still insufficient at M3 received a second prescription for 300,000 IU of oral vitamin D3. Relation between changes in 25-OH vitamin D between M3 and M0 and baseline values were assessed. Results: Patients (124) had a blood test at M3. Two (2%) had deficiency (8.1 ng/ml (7.5-8.7)) and 50 (40%) normal results (36.7 ng/ml (30.5-5.5)). Seventy-two (58%) were insufficient (23.6 ng/ml (13.8-29.8)) and received a second prescription for 300,000 IU of oral vitamin D3. Of the 50/124 patients who had normal results at M3 and did not receive a second prescription, 36 (72%) had a test at M6. Seventeen (47%) had normal results (34.8 ng/ml (30.3-42.8)) and 19 (53%) were insufficient (25.6 ng/ml (15.2-29.9)). Of the 72/124 patients who receive a second prescription, 54 (75%) had a test at M6. Twenty-eight (52%) had insufficiency (23.2 ng/ml (12.8-28.7)) and 26 (48%) had normal results (33.8 ng/ml (30.0-43.7)). At M3, 84% patients achieved a 25-OH vitamin D level >20 ng/ml. The lowest the baseline value, the highest the change after 3 months (negative relation with a correlation coefficient r = −0.3, p = 0.0007). Conclusions: We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients. [ABSTRACT FROM AUTHOR]

Background: Changes of body composition occur with aging and influence health status. Thus accurate methods for measuring fat-free mass (FFM) in the elderly are essential.Objective: The purpose of this study was to compare FFM obtained by three bioelectrical impedance analysis (BIA) published formulas specific for the elderly and one equation intended for all age groups, with FFM derived from dual-energy X-ray absorptiometry (FFM(DXA)), in healthy elderly subjects.Methods: Healthy Caucasian subjects over 65 years (106 women, age 75 +/- 6.2, body mass index 25.2 +/- 4.1 and 100 men, age 74.6 +/- 6.6, body mass index 25.8 +/- 3.0) were measured by DXA (Hologic QDR-4500) and BIA (Xitron, 50 kHz). FFM(BIA) was calculated by the published formulas of Deurenberg, Baumgartner, Roubenoff and Kyle and compared to FFM(DXA) by a Bland-Altman analysis.Results: The Deurenberg and Roubenoff BIA formulas underestimated FFM compared to DXA by -7.1 and -2.9 kg in women and -6.7 and -2.3 kg in men, respectively. The Baumgartner formula overestimated FFM by 4.3 kg in women and 1.4 kg in men. The Kyle formula showed differences of 0.0 kg in women and 0.2 kg in men, and the limits of agreement of FFM(BIA (Kyle)) relative to FFM(DXA) were -3.3 and +3.3 kg for women and -3.8 and +4.3 kg for men.Conclusion: The Kyle BIA formula accurately predicts FFM in elderly Swiss subjects between 65 and 94 years, with a body mass index of 17 to 34.9 kg/m(2). The other BIA formulas developed especially for the elderly are not valid in this population. [ABSTRACT FROM AUTHOR]

Background: This report describes a new strategy for the care of patients with osteogenesis imperfecta, based on an interdisciplinary team working. Thereby, we aim at fulfilling three main goals: offering thorough coordinated management for all, and improving physical activity and quality of life of the patients., Aim: With rare diseases such as osteogenesis imperfecta (OI), patients and their family often suffer from inadequate recognition of their disease, poor care coordination and incomplete information. A coordinated interdisciplinary approach is one possible solution for providing both comprehensive and cost-effective care, with benefits for patient satisfaction. Poor physical activity and impaired quality of life represent a considerable burden for these patients. To better address these issues, in 2012 we created an interdisciplinary team for the management of OI patients in our University Hospital Centre (CHUV, Lausanne University Hospital,). In this article we describe the implementation of this interdisciplinary care strategy for patients suffering from OI, and its impact on their physical activity and quality of life., Methods: All patients from the French part of Switzerland were invited to join us. We proposed two complementary evaluations: the initial interdisciplinary evaluation and a yearly follow-up during a special day &ndash; the &ldquo;OI day&rdquo;. This day features specialised medical appointments adapted to each patient&rsquo;s needs, as well as lectures and/or workshops dedicated to patients&rsquo; and families&rsquo; education. Our first aim was to propose for each patient the same management, from diagnosis to the bone health evaluation and physical therapy advice. Our second aim was to evaluate the evolution of physical activity, quality of life (measured by EQ-5D, SF-36 and a dedicated questionnaire) and satisfaction of patients and their families. Here we report both the initial and the long-term results., Results: Since 2012, 50 patients from the French part of Switzerland received the personalised medical evaluation. All of the patients included in this study had the same initial evaluation and at least one participation in an OI Day. All patients had an adaptation of their bone acting drugs. Over a 7-year period, 62% of inactive patients started some physical activity, and 44% of patients who were not involved in any athletic activity started participating in sports. The mean EQ-5D increased from 0.73 to 0.75 (p = 0.59). The mean physical SF36 (musculoskeletal function) score was 59.09 &plusmn; 22.72 and improved to 65.79 &plusmn; 21.51 (p = 0.08), whereas it was 68.06 &plusmn; 20.05 for the mental SF36 without alteration during follow-up. The OI day was revealed to be useful, it contributed to improvement in continuity of care and helped families to better understand the OI patients&rsquo; health., Conclusions: Our interdisciplinary approach aimed at offering the same thorough management for all patients from the French part of Switzerland, and at improving both the physical activity and the satisfaction of the patients and their family. This report is a basis for future work focusing on the effect of bone fragility and the impact of OI on patients&rsquo; social relations.

We evaluated the associations between nutrients, dietary patterns or compliance to dietary guidelines and bone health among postmenopausal women from the CoLaus/OsteoLaus cohort. Postmenopausal women with osteoporosis consume a high amount of vegetables but insufficient amount of dairy products and calcium to benefit from their adherence to dietary guidelines., Introduction: Diet plays a significant role in the prevention of osteoporosis (OP). We evaluated the associations between nutrients, dietary patterns or compliance (expressed in odds of meeting) to dietary Swiss guidelines and bone health (T score < - 2.5 SD, TBS < 1230) among postmenopausal women., Methods: One thousand two hundred fifteen women (64.3 ± 7.5 years) from the CoLaus/OsteoLaus cohort (Lausanne, Switzerland) had their dietary intake assessed using a validated food frequency questionnaire. Bone mineral density (BMD), trabecular bone score (TBS) and vertebral fractures were evaluated with DXA. OP risk factors, calcium supplements (> 500 mg) and prevalent major OP fractures were assessed by questionnaire., Results: One hundred eighty of 1195 women had OP according to BMD, 87/1185 a low TBS and 141/1215 prevalent major OP fractures. In multivariate analysis (adjusted for total energy intake, age, antiosteoporotic treatment, educational level, BMI, sedentary status and diabetes), OP women consumed more vegetable proteins (21.3 ± 0.4 vs 19.6 ± 0.2 g/day), more fibres (18.2 ± 0.5 vs 16.5 ± 0.2 g/day), less animal proteins (40.0 ± 1.1 vs 42.8 ± 0.4 g/day), less calcium (928 ± 30 vs 1010 ± 12 mg/day) and less dairy products (175 ± 12 vs 215 ± 5 g/day), all p ≤ 0.02. According to guidelines, OP women had a tendency to higher compliance for vegetables (OR (95% CI) 1.50 (0.99-2.26)) and a lower compliance for dairy (OR (95% CI) 0.44 (0.22-0.86)) than those without OP. Women taking calcium supplements consumed significantly higher amounts of dairy products. No association was found between TBS values or prevalent OP fractures and any dietary components., Conclusion: Postmenopausal women with OP consume a high amount of vegetables but insufficient amount of dairy products and calcium. TBS does not seem to be influenced by diet.

Context: Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results., Objective: To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo., Design and Intervention: Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration., Setting and Participants: 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment., Main Outcome Measures: One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed., Results: Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex., Conclusions: Over 1-year levothyroxine had no effect on bone health in older adults with SHypo., Registration: ClinicalTrial.gov NCT01660126 and NCT02491008., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To maximise the potential benefits to ruminants from sainfoin, plant breeding should focus on developing varieties with predictable condensed tannin (CT) profiles. Little is known about whether and to what extent accession and environment influence sainfoin CT structures. We sought to investigate the likely extent of accession and environment effects on CT characteristics of sainfoin. Four single-flowering (Communis) accessions and two multiple-flowering (Bifera) accessions, grown at three sites and collected at two harvest times were used. Sainfoin CTs were characterised by thiolytic degradation and by high-performance liquid chromatography-gel permeation chromatography (HPLC-GPC). Also, CT concentration measured earlier by the HCl-butanol method was compared with that from thiolysis., Results: Thiolysis revealed that accession and harvest influenced most CT structural attributes. Bifera CTs eluted as single peaks (Mp  < 6220 Da) in HPLC-GPC across the two harvests and two sites, whereas Communis generated two to three CT peaks, which included a peak (Mp  ≤ 9066 Da) in the second harvest. A discrepancy was observed in CT concentrations measured by the two methods., Conclusion: CTs from Bifera accessions had more stable and predictable characteristics across harvests and sites and this could be of interest when breeding sainfoin., (© 2013 Society of Chemical Industry.)

Background: To objectively compare the mood profiles of users of malaria chemoprophylaxis regimens (atovaquone-proguanil, chloroquine-proguanil, doxycycline, or mefloquine) in a group of nonimmune tourists to sub-Saharan Africa., Methods: In a randomized, double-blind, four-arm study with placebo run-in phase conducted at travel clinics in Switzerland, Germany, and Israel, we compared moods and feelings in chemoprophylaxis users (n= 547) by administering the standardized "Profile of Mood States" (POMS) questionnaire. This is designed to provide data on six categories of feelings: tension, depression, anger, vigor, fatigue, and confusion. The questionnaire was administered at four time points: recruitment (T1), 13 to 11 days before departure (T2), 6 to 4 days before departure (T3), and 7 to 14 days after return from Africa (T4)., Results: There were no significant differences with respect to overall mood impact between the medication arms. All scores were in the normal range, and no means were more than 1 SD from the norm. The POMS data were reanalyzed with respect to sex, age, medication group, and control time points (T1-T4). There were significant interaction effects between sex and medication group--women in the mefloquine group showed more "fatigue" (p= .011) and "confusion" (p= .011) than men. Significant effects of age group (below median age 34 y vs median age and above) were noted on the "tension" and "fatigue" scales in that less "tension" (p= .045) and less "fatigue" (p= .000) were noted in those aged 34 years and older. Younger participants, aged <34 years, reported more "confusion" (p= .013) at T2 than at T1 and T4., Conclusions: Although the overall mood profiles were similar for the users of any of the standard malaria chemoprophylaxis regimens, we found that women using mefloquine showed more fatigue and confusion than men and that younger persons aged less than 34 years, regardless of chemoprophylaxis used, reported more tension and fatigue than their older counterparts.

Unlabelled: To compare the prediction of hip fracture risk of several bone ultrasounds (QUS), 7062 Swiss women > or =70 years of age were measured with three QUSs (two of the heel, one of the phalanges). Heel QUSs were both predictive of hip fracture risk, whereas the phalanges QUS was not., Introduction: As the number of hip fracture is expected to increase during these next decades, it is important to develop strategies to detect subjects at risk. Quantitative bone ultrasound (QUS), an ionizing radiation-free method, which is transportable, could be interesting for this purpose., Materials and Methods: The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study is a multicenter cohort study, which compared three QUSs for the assessment of hip fracture risk in a sample of 7609 elderly ambulatory women > or =70 years of age. Two QUSs measured the heel (Achilles+; GE-Lunar and Sahara; Hologic), and one measured the heel (DBM Sonic 1200; IGEA). The Cox proportional hazards regression was used to estimate the hazard of the first hip fracture, adjusted for age, BMI, and center, and the area under the ROC curves were calculated to compare the devices and their parameters., Results: From the 7609 women who were included in the study, 7062 women 75.2 +/- 3.1 (SD) years of age were prospectively followed for 2.9 +/- 0.8 years. Eighty women reported a hip fracture. A decrease by 1 SD of the QUS variables corresponded to an increase of the hip fracture risk from 2.3 (95% CI, 1.7, 3.1) to 2.6 (95% CI, 1.9, 3.4) for the three variables of Achilles+ and from 2.2 (95% CI, 1.7, 3.0) to 2.4 (95% CI, 1.8, 3.2) for the three variables of Sahara. Risk gradients did not differ significantly among the variables of the two heel QUS devices. On the other hand, the phalanges QUS (DBM Sonic 1200) was not predictive of hip fracture risk, with an adjusted hazard risk of 1.2 (95% CI, 0.9, 1.5), even after reanalysis of the digitalized data and using different cut-off levels (1700 or 1570 m/s)., Conclusions: In this elderly women population, heel QUS devices were both predictive of hip fracture risk, whereas the phalanges QUS device was not.

Background: Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls., Objective: The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner., Methods: In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae., Results: At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size., Conclusion: In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation.

Objective: No current studies have compared North American with European body composition parameters, i.e., fat-free mass (FFM), body fat (BF), and percentage of BF (%BF) in large populations. This study compared FFM, BF, and %BF values derived from two bioelectrical impedance analysis (BIA) equations (Geneva and National Health and Nutrition Examination Survey [NHANES]) in Swiss subjects and compared FFM, BF, and %BF values of white Swiss with those of white North American adults with the same BIA equations., Methods: Healthy adults (3714 men and 3199 women), ages 20 to 79 y, in Switzerland were measured by single-frequency BIA and compared with means and standard deviations for body mass index and body composition parameters obtained from the NHANES III study (United States; n = 2538 men, 2862 women). FFM was calculated with the Geneva and NHANES equations., Results: Mean FFMGENEVA values did not differ from FFMNHANES values in men but was significantly lower (-1.5 kg) in women. FFM and BF values in American men, who weighed 4.2 to 12.0 kg more than the Swiss men, were significantly higher (+2.1 to +6.0 kg and +1.5 to +6.4 kg, respectively) than those in the Swiss men. FFM and BF values in American women, who weighed 2.3 to 12.1 kg more than the Swiss women, were significantly higher (+1.3 to +2.1 kg and +4.8 to +11.8 kg, respectively, except FFM in subjects ages 20 to 29 y and BF in those ages 70 to 79 y) than FFMGENEVA values in Swiss women. FFM in American women was significantly lower (+1.3 and +1.9 kg) and non-significantly higher than FFMNHANES in Swiss women., Conclusion: NHANES and Geneva BIA equations estimate body composition equally well in men, but further research is necessary to determine the discrepancies in FFM between BIA equations in women. The greater weight of the American subjects yielded higher values for FFM, BF, and %BF in American than in Swiss men and women.

Objective: To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers., Design: Randomised, double blind, study with placebo run-in phase., Setting: Travel clinics in Switzerland, Germany, and Israel., Main Outcome Measure: Proportion of participants in each treatment arm with subjectively moderate or severe adverse events., Participants: 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil., Results: A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013)., Conclusions: Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.