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Background: Chordomas are rare malignant skull-base/spine cancers with devastating neurological morbidities and mortality. Unfortunately, no reliable prognostic factors exist to guide treatment decisions. This work identifies DNA methylation-based prognostic chordoma subtypes that are detectable non-invasively in plasma. Methods: Sixty-eight tissue samples underwent DNA methylation profiling and plasma methylomes were obtained for available paired samples. Immunohistochemical staining and publicly available methylation and gene expression data were utilized for validation. Results: Unsupervised clustering identified two prognostic tissue clusters (log-rank p=0.0062) predicting disease-specific survival independent of clinical factors (Multivariable Cox: HR=16.5, 95%CI: 2.8-96, p=0.0018). The poorer-performing cluster showed immune-related pathway promoter hypermethylation and higher immune cell abundance within tumours, which was validated with external RNA-seq data and immunohistochemical staining. The better-performing cluster showed higher tumour cellularity. Similar clusters were seen in external DNA methylation data. Plasma methylome-based models distinguished chordomas from differential diagnoses in independent testing sets (AUROC=0.84, 95%CI: 0.52-1.00). Plasma methylomes were highly correlated with tissue-based signals for both clusters (r=0.69 & 0.67) and leave-one-out models identified the correct cluster in all plasma cases. Conclusions: Prognostic molecular chordoma subgroups are for the first time identified, characterized, and validated. Plasma methylomes can detect and subtype chordomas which may transform chordoma treatment with personalized approaches tailored to prognosis.
The sustainability of rigid packaging can be increased by using biocomposites in packaging. Existing frameworks have some limitations such as are made to assess a few aspects, conventional packaging parameters are considered, etc. Biocomposite has a slightly different scenario at various life cycle stages, like the end-of-life cycle process. To assess the sustainability of biocomposite rigid packaging, we must consider parameters related to the biocomposite-based rigid packaging materials life cycle. These are categorised into different aspects of sustainability and life cycle phases.
This study aimed: to evaluate the association between coronavirus disease 2019 infection and olfactory and taste dysfunction in patients presenting to the out-patient department with influenza-like illness, who underwent reverse transcription polymerase chain reaction testing for coronavirus; and to determine the sensitivity, specificity, and positive and negative predictive values of olfactory and taste dysfunction and other symptoms in these patients.
Methods
Patients presenting with influenza-like illness to the study centre in September 2020 were included in the study. The symptoms of patients who tested positive for coronavirus on reverse transcription polymerase chain reaction testing were compared to those with negative test results.
Results
During the study period, 909 patients, aged 12–70 years, presented with influenza-like illness; of these, 316 (34.8 per cent) tested positive for coronavirus. Only the symptoms of olfactory and taste dysfunction were statistically more significant in patients testing positive for coronavirus than those testing negative.
Conclusion
During the pandemic, patients presenting to the out-patient department with sudden loss of sense of smell or taste may be considered as positive for coronavirus disease 2019, until proven otherwise.
Ketamine, an N-methyl-d-aspartate receptor antagonist, has been “repurposed” as a rapid-acting antidepressant for treatment-resistant depression (TRD). The s-enantiomer of ketamine, “esketamine,” was FDA approved for TRD and depressive symptoms in adults with major depressive disorder with suicidal ideations/behaviors. Intravenous (IV) ketamine, although financially less expensive, is often not covered by insurance and intranasal (IN) esketamine, although covered by insurance can be expensive. There is a paucity of literature on efficacy data comparing subanesthetic IV ketamine and IN esketamine for TRD in a real-world scenario. Thus, we conducted this study comparing the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among TRD patients.
Methods
This was an observational study where we included adults (≥18 years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5 mg/kg, infused over 40 minutes) or up to 8 intranasal (IN) esketamine (56/84 mg) treatments for TRD at the Mayo Clinic Depression Center. Depression symptoms were measured utilizing the self-report 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale before and 24 hours after ketamine/esketamine treatment. Remission and response were defined as QIDS-SR 16 score ≤5 and ≥50% change in QIDS-SR 16, respectively. Continuous variables are reported as means ± SD and categorical variables as counts and percentages. The Wilcoxon rank-sum test was used to compare continuous variables. Chi-square and Fisher’s exact tests were used to compare categorical variables. The number of treatments to remission/response was calculated.
Results
Sixty-three adults with TRD, middle-aged (47.0 ± 12.1 years), predominantly female (65%), of which 76% (n = 48) and 24% (n = 15) received IV ketamine and IN esketamine, respectively. Mean (SE) change in QIDS-SR 16 score was −8.7 ± 0.7 (P < .001), a significant reduction (improvement) from baseline (mean ± SD = 17.6 ± 3.7). Overall remission and response rates were 36.5% and 55.6%, respectively in the acute phase. Response (56.3% vs 53.3%) and remission rates (39.6% vs 26.7%) were similar among patients who received IV ketamine or IN esketamine, respectively (P > .05). The mean number of treatments received to achieve response (2.5 ± 1.6 vs 4.6 ± 2.1) and remission (2.4 ± 1.3 vs 6.3 ± 2.4) were significantly lower among patients who received IV ketamine compared to IN esketamine (P < .005). Most patients tolerated both treatments well.
Conclusion
Intravenous ketamine and intranasal esketamine showed similar response/remission in TRD patients but the number of treatments required to achieve response/remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions.
Asteroid and cometary impacts have been considered one of the possible routes for exogenous delivery of organics to the early Earth. It is well established that amino acids can be synthesized due to impact-driven shock processesing of simple molecules and that amino acids can survive the extreme conditions of impact events. In the present study, we simulate impact-induced shock conditions utilizing a shock tube that can maintain a reflected shock temperature of about 5,500 K for 2 ms time scale. We have performed shock processing of various combinations of amino acids with subsequent morphological analysis carried out using Scanning Electron Microscope (SEM), revealing that the shock processed amino acids demonstrate an extensive range of complex structures. These results provide evidence for the further evolution of amino acids in impact-induced shock environments leading to the formation of complex structures and thus providing a pathway for the origin of life.
Using a machine-learning model, we examined drivers of antibiotic prescribing for antibiotic-inappropriate acute respiratory illnesses in a large US claims data set. Antibiotics were prescribed in 11% of the 42 million visits in our sample. The model identified outpatient setting type, patient age mix, and state as top drivers of prescribing.
The ai/m of this study was to compare the self-reported confidence of novices in using a smartphone-enabled video otoscope, a microscope and loupes for ear examination and external ear canal procedures.
Method
Medical students (n = 29) undertook a pre-study questionnaire to ascertain their knowledge of techniques for otoscopy and aural microsuction. Participants underwent teaching on ear anatomy, examination and procedural techniques using a microscope, loupes and smartphone-enabled video otoscopes. Confidence and preference using each modality was rated using a Likert-like questionnaire.
Results
After teaching, all modalities demonstrated a significant increase in confidence in ear examination (p < 0.0001). Confidence in using the smartphone-enabled otoscope post-teaching was highest (p = 0.015). Overall, the smartphone-enabled video otoscope was the preferred method in all other parameters assessed including learning anatomy or pathology (51.72 per cent) and learning microsuction (65.51 per cent).
Conclusion
Smartphone-enabled video otoscopes provide an alternative approach to ear examination and aural microsuction that can be undertaken outside of a traditional clinical setting and can be used by novices.
Existence of genetic divergence, appropriate characterization of breeding lines for economically important traits and determining parents with favourable alleles is the crux of crop genetic improvement programmes. This study is the first report of unravelling genetics and potential of petaloid-type cytoplasmic male sterile (pt-CMS) lines in carrot. Ten pt-CMS lines were crossed with 10 inbreds in line × tester mating fashion to generate 100 testcross progenies. Nutritional profiling of the 100 testcrosses progenies along with 20 parental types was carried out for two consecutive years for eight important traits to identify superior combiners. The pooled analysis revealed that the carotenoid content in root is under the genetic control of major genes (oligogenic). The pooled analysis revealed less than unity value of σ2A/D and σgca2/σsca2 for majority of the traits depicting preponderance of non-additive gene effects. The pt-CMS lines KT-28A, Kt-62A, KT-80A and KT-95A were identified as good combiners for carotenoids. The cross combination, KT-98A × KS-50 identified as the best heterotic combiner for CUPRAC and FRAP content over the years. Similarly, the combinations, KT-62A × KS-21, KT-80A × New Kuroda and KT-62A × KS-59 were found promising across the years for developing nutritionally rich F1 hybrids. The interaction analysis among the different antioxidant traits and plant pigments unveiled the scope of simultaneous improvement.
Maize and Imperata cylindrica have been utilized globally as a pollen source for induction of haploids in wheat through chromosome elimination technique. Pollen parents with a higher haploid induction rate are desired for recovering the high frequency of haploids in wheat and related species. The present investigation was carried out with the aim to assess haploid induction efficiency of diverse germplasm of maize and I. cylindrica in different generations of intra and intergeneric crosses of hexaploid and tetraploid wheat and triticale-wheat derivatives. Crosses of twenty-six lines (female) with each of two I. cylindrica and twenty-one maize genotypes (testers) were evaluated for four haploid induction parameters viz., pseudoseed formation frequency (PFF), embryo formation frequency (EFF), haploid regeneration frequency (HRF) and haploid formation frequency (HFF). I. cylindrica outperformed maize in haploid induction rate with a frequency of embryos formed with I. cylindrica (18.39%) were significantly higher as compared to maize (4.08%). In the case of I. cylindrica genotype Ic-ye identified best with mean EFF of 30.55, 14.48 and 25.43% for hexaploids, tetraploids and triticale × wheat derivatives, respectively whereas in the case of maize genotype HPMC-60 performed best with EFF of 12.61% for hexaploids, HPMC-58 (12.58%) for tetraploids and HPMC-16 for triticale × wheat derivatives with EFF of 8.91%. I. cylindrica genotype Ic-ye and maize genotypes HPMC-14, HPMC-53, HPMC-60, HPMC-64 with significantly positive GCA for haploid induction parameters may be utilized as efficient pollen parents for recovering higher frequency of haploids in wheat.
Tomato is a pivotal vegetable crop worldwide concerning human nutrition, economy and in service to biotechnology. Tomato leaf curl virus (ToLCV) is a begomovirus transmitted through the whitefly (Bemisia tabaci) and is responsible for severe losses in tomato production. In this context, the current investigation was carried out to determine heterotic combiners with high yield, resistance to ToLCV and mode of gene action for economically important traits. For this, 11 prescreened inbred lines were crossed in a half diallel fashion to generate 55 F1 hybrids. The 55 crosses with 11 parents and commercial checks were evaluated for different horticultural traits and resistance to ToLCV. The molecular validation with SCAR markers TG0302 and SCAR1 confirmed the presence of ToLCV-resistant genes in parents and their crosses. The hybrid IIHR-2902 × IIHR-2852 showed the presence of both Ty-2 and Ty-3 alleles in the homozygous state. The estimation of σSCA2 and σGCA2 was significant. It also indicated that the genetic control of target traits was under additive and non-additive gene effects. The values of σA/D2 along with σGCA2/σSCA2 found to be less than unity indicates the preponderance of non-additive gene action in the expression of the studied traits except for percent disease incidence. The parental line IIHR-2919 was the best combiner for fruit and yield traits. The cross combinations IIHR-2913 × IIHR-2898 exhibited significantly higher economic heterosis for yield along with the presence of Ty-2 and Ty-3 genes. The study paves the way for breeding high yielding and ToLCV-resistant hybrids in tomato.
Population-based surveys commonly use point-of-care (POC) methods with capillary blood samples for estimating Hb concentrations; these estimates need to be validated by comparison with reference methods using venous blood. In a cross-sectional study in 748 participants (17–86 years, 708 women, Hb: 5·1 to 18·2 g/dl) from Hyderabad, India, we validated Hb measured from a pooled capillary blood sample by a POC autoanalyser (Horiba ABX Micros 60OT, Hb-C-AA) by comparison with venous blood Hb measured by two reference methods: POC autoanalyser (Hb-V-AA) and cyanmethemoglobin method (Hb-V-CM). These comparisons also allowed estimation of blood sample-related and equipment-related differences in the Hb estimates. We also conducted a longitudinal study in 426 participants (17–21 years) to measure differences in the Hb response to iron folate (IFA) treatment by the capillary blood POC method compared with the reference methods. In the cross-sectional study, Bland–Altman analyses showed trivial differences between source of blood (Hb-C-AA and Hb-V-AA; mean difference, limits of agreement: 0·1, −0·8 to 1·0 g/dl) and between analytical methods (Hb-V-AA and Hb-V-CM; mean difference, limits of agreement: < 0·1, −1·8 to 1·8 g/dl). Cross-sectional anaemia prevalence estimated using Hb-C-AA did not differ significantly from Hb-V-CM or Hb-V-AA. In the longitudinal study, the Hb increment in response to IFA intervention was not different when using Hb-C-AA (1·6 ± 1·7 g/dl) compared with Hb-V-AA (1·7 ± 1·7 g/dl) and Hb-V-CM (1·7 ± 1·7 g/dl). The pooled capillary blood–autoanalyzer method (Hb-C-AA) offers a practical and accurate way forward for POC screening of anaemia.
Anthracnose caused by Colletotrichum truncatum is a major soybean disease in India. Genetic resistance is the viable option to combat yield losses due to this disease. In the current study, 19 soybean genotypes were evaluated for anthracnose disease resistance at five locations (Medziphema, Palampur, Dharwad, Jabalpur and Indore) for three consecutive years (2017–2019) to identify stable and superior genotypes as resistant sources and to elucidate genotype (G) × environment (E) interactions. Genotype effect, environment effect and G × E interactions were found significant (P < 0.001) where G × E interactions contributed highest (42.44) to the total variation followed by environment (29.71) and genotype (18.84). Through Weighted Average of Absolute Scores (WAASB) stability analysis, PS 1611 (WAASB score = 0.33) was found to be most stable and through WAASBY superiority analysis NRC 128 (WAASBY score = 94.31) and PS 1611 (WAASBY score = 89.43) were found to be superior for mean performance and stability. These two genotypes could be candidate parents for breeding for durable and stable anthracnose resistance. Through principal component analysis, disease score was found to be positively associated with relative humidity, wind speed at 2 m above ground level, effect of temperature on radiation use efficiency and global solar radiation based on latitude and Julian day. Among the five locations, Indore was found to be highly discriminative with the highest mean disease incidence and could differentiate anthracnose-resistant and susceptible genotypes effectively, therefore can be considered an ideal location for breeding for field resistance against anthracnose disease.
Fall armyworm, Spodoptera frugiperda (J. E. Smith) is a polyphagous and highly destructive invasive insect pest of many crops. It was recently introduced into India and widely reported in almost all parts of India. Development of a temperature-based phenology model for predicting its rate of development and distribution will help in understanding the establishment and further spread of introduced invasive insect pests. Development, survival and reproduction parameters of S. frugiperda at six constant temperature conditions (15, 20, 25, 27, 30 and 35°C) were investigated and further validated with data generated under fluctuating temperature conditions. The estimated lower developmental threshold temperatures were 12.1°C for eggs, 11°C for larvae, 12.2°C for pupae, 15.13°C for males and 12.66°C for females. Degree-day (DD) requirements for the development of the different stages of S. frugiperda were 50, 250 and 200 DD for egg, larva and pupa, respectively. The best-fitted functions were compiled for each life stage to yield a phenology model, which was stochastically simulated to estimate the life table parameters. The developed phenology model predicted temperature ranges between 27 and 30°C as favourable for S. frugiperda development, survival and reproduction. The results revealed that maximum net reproductive rate (215.66 females/female/generation) and total fecundity (981.08 individuals/female/generation) were attained at 30°C constant temperature. The mean length of generations decreased from 74.29 days at 15°C to 38.74 days at 30°C. The maximum intrinsic rate of increase (0.138 females/female/day) and shortest doubling time (4.9 days) were also observed at 30°C. Results of simulated life table parameters showed high temperature-dependent development of S. frugiperda and complete development within all the tested constant temperature ranges (15–35°C). Simulated life table parameters for predicting risk indices of S. frugiperda in India indicated a significant increase in activity indices and establishment risk indices with a higher number of generations during future (2050 and 2070) climatic change scenarios compared to present conditions. Our results indicate that India will be highly suitable for the establishment and survival of S. frugiperda in future time periods.
This study aimed to evaluate serum otolin-1 levels in patients with benign paroxysmal positional vertigo and to compare these levels with healthy individuals.
Method
This was a case-control study. After obtaining institutional ethical committee clearance, the serum level of otolin-1 was calculated in adult individuals (18–75 years old) who were divided into group 1 (patients presenting with benign paroxysmal positional vertigo) and group 2 (healthy patients without benign paroxysmal positional vertigo as the control group). Data analysis was carried out to compare the serum levels in the cases and controls. A p-value less than 0.05 was considered significant.
Results
A total of 70 age-matched individuals (cases, n = 40; controls, n = 30) were included in the study. The mean serum level of otolin-1 was 636.8 pg/ml (range, 259–981 pg/ml) in the group of patients with benign paroxysmal positional vertigo and 236.2 pg/ml (range, 189–370 pg/ml) in the control group. The difference was statistically significant (p = 0.0000).
Conclusion
The serum levels of otolin-1 in patients with benign paroxysmal positional vertigo are significantly higher compared with individuals without benign paroxysmal positional vertigo.
Acquisition and germination of seeds are the most desired targets for the improvement of vegetatively propagated crops. In the present study, we developed a potential embryo germination protocol for the Red Globe grape cultivar having a low seed germination rate. Three grape berries at different developmental stages, viz. 50, 60 and 70 days after flowering (DAF), were selected for in-vitro embryo germination. Three growth media, namely Emershad and Ramming (ER), Nitsch and Nitsch (NN) and Murashige and Skoog (MS), and plant growth regulators (benzyl amino purine (BA), 0.5, 0.7 and 0.9 mg/l; indole butyric acid (IBA), 1.0, 1.5 and 2.0 mg/l; and gibberellic acid (GA), 0.1, 0.3 and 0.9 mg/l) were screened individually in different combinations with three amino acids, namely cysteine, glutamine and proline (2.0 μmol/l each). The maximum embryos germination percentage recorded at 70 DAF was 63.33, 47.78 and 45.56% in ER, NN and MS media, respectively, supplemented with 0.9 mg/l BA, 2.0 mg/l IBA, 0.9 mg/l GA and 2.0 μmol glutamine. Glutamine was found to have the most significant impact, and it improved the rescued embryos germination. The present study provides a potential recipe for a medium that can facilitate efficient germination of grape embryos.
Originating in China in December 2019, coronavirus disease 2019 (COVID-19) rapidly spread to more than 216 countries in the world by May 2020. Because dentists are at a higher risk of contracting the disease, the present study assessed the fear and anxiety among dental practitioners of becoming infected with COVID-19.
Methods:
An online cross-sectional questionnaire survey comprising of 9 questions was conducted among dental practitioners of Telangana. Age, gender, qualification, type of practice, years of practice, and place of residence were the demographic variables recorded. The response to each question was recorded in a YES or NO format, and mean fear score was calculated to categorize answers into low and high levels of fear. Comparison of mean fear score was done using t-test for 2 variables and analysis of variance for 3 or more than 3 variables. Multiple logistic regression analysis of the levels of fear with demographic variables was done. P < 0.05 was considered statistically significant.
Results:
The mean fear and anxiety score of this study population reported was high 6.57 ± 2.07, with 58.31% of the population presenting with a low level of fear and anxiety. Only qualification (P = 0.045) and gender (P = 0.035) revealed a significant difference in fear to Q7and Q8, respectively. Irrespective of the age, gender, qualification, type of practice, and years in practice, the levels of fear reported in the present study were very similar. Respondents between 41 and 60 y of age (6.70 ± 2.01 y) and those with individual practices (6.70 ± 2.06 y) exhibited high fear scores.
Conclusions:
The present study demonstrates cross-sectional data of fear and anxiety among dental practitioners during the COVID-19 outbreak. Heightened levels of fear observed in this study call for a nationwide analysis of fear among dentists and deliberate management strategies for the same.
This paper reports an integration of dual band microstrip antenna with thin film amorphous silicon solar cell which creates a wearable system to harvest microwave energy. The multiple layers in the encapsulation of the thin film solar cell are used as a substrate for microstrip antenna. The rectifier and matching circuit are designed on cotton jeans material and the whole system is mechanically supported by the foam of 5 mm thick. The performance of the antenna is studied for the mechanical bending condition. The device has maintained good power conversion efficiency. The efficiency of the voltage doubler is tested by varying radio frequency power levels from −30 to10 dBm. The voltage doubler conversion efficiency at 1.85 and 2.45 GHz are 58 and 43%, respectively, for a load of 7.5 kΩ for an input power level of −5 dBm.
The Crisis Resolution Home Treatment team (CRHT) provides comprehensive care and support to individuals experiencing acute mental health difficulties in the community. It offers a same day assessment and provides an alternative to hospital admission by providing intensive intervention in the community. In case of hospitalisation, the CRHT can assist in minimising inpatient stay.
Handsworth and Ladywood are two major residential areas in Birmingham with high level deprivation and a population of approximately 9000. The study reviews the completeness and efficacy of CRHT intervention.
Methods
The study retrospectively examined 100 consecutive referred case notes during June and July 2008. That period was about four months prior to the start of the study which provided enough time for the completion of a home care episode. Data was gathered and assessed statistically.
Results
62% of referrals were assessed on the same day and 27% within one day of referrals. 11% of referrals were new to psychiatric services. Referrals were from Accident and Emergency (32%), Community Mental Health Teams (22%) and general practitioners (8%). There were three and two assessors in 60% and 100% of cases respectively. A doctor was always present for all the assessments. Eighty-three percent of the referrers were notified of the assessment outcome the same day and 14% the following day.
Conclusions
The CRHT provides an effective care to psychiatric patients with acute needs. The organised nature of this service reduces hospitalisation and ensures that needs of patients experiencing acute mental health difficulties are met in the community.
This study assesses the experiences of Internationally Recruited (IR) Consultant Psychiatrists focussing on the recruitment process and its adherence to the DH guidance.
Methods:
Eighty-eight IR consultant psychiatrists from different countries were mailed a 13-item questionnaire assessing their experiences regarding various aspects of the recruitment process.
Results:
48% IR psychiatrists responded; 97% were from India. The recruitment process was generally satisfactory with perceived gaps in support from various stakeholders. Inconsistent experiences were reported regarding induction, mentorship, clinical responsibilities, and racial discrimination.
Conclusions:
The recruitment process adhered to the good practice guidelines (DH) within the broad framework of clinical governance. It is important that any such future initiatives have in place appropriate supervision, mentorship, and a sufficient period of induction including exposure to the relevant systems and procedures to ensure good quality service with a view to minimise risk for patients as well as staff. There are limitations to the applicability of the results to the wider group of professionals.
B-vitamin insufficiency is associated with depression but it is uncertain if treatment with these is effective in prevention or treatment.
Objectives and Aims
1. To determine if daily supplementation with B-vitamins enhances response to antidepressants.
2. Systematic review and meta-analysis of randomised, placebo-controlled trials of B-vitamins for depressive symptoms in adults.
Methods
1. The B-VITAGE trial is a 52 week randomised, double-blind, placebo-controlled trial of citalopram together with vitamin B12, B6 and folic acid in older adult participants with major depression.
2. Systematic review of 13 eligible trials of B-vitamin supplementation for the reduction, remission and prevention of clinically significant depressive symptoms.
Results
Remission was achieved by 78.1% and 79.4% of participants treated with placebo (n=76) and vitamins (n=77) by week 12 (p=0.328), and by 75.8% and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio, OR=2.49; 95% confidence interval, 95%CI=1.12,5.51). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamin group (OR=0.33, 95%CI=0.12,0.94).
Short-term use of vitamins did not improve depressive symptoms in adults with major depression treated with antidepressants (standardised mean difference=-0.12, 95% CI=-0.45,0.22), but more prolonged consumption decreased the risk of relapse (OR=0.33, 95%CI=0.12,0.94) and the onset of clinically significant symptoms in people at risk (risk ratio=0.65, 95%CI=0.43,0.98).
Conclusions
Short-term use of B-vitamins does not appear to benefit depressive symptoms although longer use may enhance and sustain antidepressant response and decrease the risk of relapse or onset of clinically significant depression.