Moderate Adverse Effects Research Articles

Reporting at Least One Adverse Effect Post-COVID-19 Vaccination From Primary Health Care in Muscat.

IntroductionVaccinations against COVID-19 were licensed with limited testing assurances to the public triggering a widespread hesitancy around expected adverse reactions. Limited data was reported from Arabian Gulf countries on vaccine adverse effects.ObjectivesThis study looked at the rate of reporting at least one side effect post-COVID-19 vaccination and its associated factors (sociodemographic characteristics, clinical condition, and type of vaccines). Additionally, questions about safety and willingness to recommend them were included.Study designPhone interviews on post-COVID-19 vaccination adverse effects were utilized to record responses related to reporting at least one side effect post vaccinations across the studied variables. Data collection continued for two months (from 1st March to 30th April 2021).MethodologyParticipants were adults (Omani citizens and non-citizens) who received AstraZeneca (AZ) or Pfizer (PF) vaccines from primary care facilities in Muscat and were randomly selected from the health information system. Responses were saved in a bespoke Google form/questionnaire. Chi-squared tests were utilized to determine potential factors associated with the dependent variable.ResultsA total of 753 participants completed the phone interviews. The mean age was 52 (3.5), males (54.1%), and 65.1% were Omanis. Hypertension (39.7%), diabetes (34.1%), and asthma (16.7%) were the commonest comorbidities. AZ and PF were administered to 78% and 22% of the participants. Of them, 49.8% reported at least one adverse effect post-COVID-19 vaccination.The proportion of participants with at least one adverse effect was significantly more in individuals who were younger, females, with more than secondary education, and employed (p value < 0.001, 0.01, <0.001, and <0.001, respectively). There was no severe reaction (anaphylactic shock) to the vaccines, and most adverse effects were mild-moderate. The proportion of individuals who reported adverse effects were higher with AZ vs PF (53% vs 38.6, p = 0.001). The most common reported localized adverse effects were pain and tenderness (28.3% and 12.1%). Fever and body aches were the commonly reported systemic adverse effects (33.5% and 29.2%).The safety of COVID-19 vaccines was well perceived, and most participants were willing to recommend them to others.ConclusionsThe current study confirms findings from existing literature on the mild to moderate adverse effects of AZ and PF vaccines. Despite the subjective nature of this study, it is reassuring that the studied COVID-19 vaccines can be administered safely. However, more longitudinal studies are needed to test their efficacy in disease prevention.

Assessment of biochemical, hematological and behavioral biomarkers of Cyprinus carpio on exposure to a type-II pyrethroid insecticide Alpha-cypermethrin

This study assessed some important physiological biomarkers of freshwater edible fish Cyprinus carpio following exposure to 10 % (T1) and 20 % (T2) sublethal concentrations of Alpha-cypermethrin (A-cyp) over a total period of 45 days. Behavioral responses were noticed and Kaplan-Meier survival curves were prepared during acute toxicity study. Total serum protein concentration, total erythrocyte count, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and total leukocytes count were decreased significantly (p < 0.05), while the blood glucose, total serum lipid concentration, and clotting time were increased significantly (p < 0.05) over control. The most affected fish group and most significantly altered biomarker under toxic stress of A-cyp were identified using integrated biomarker response (IBR). The biomarker response index (BRI) values measured the overall health status of the treated fish and indicated that moderate adverse effects were exerted on the fish group exposed to T2 for 45 days.

Emerging minimally invasive transurethral treatments for benign prostatic hyperplasia: a systematic review with meta-analysis of functional outcomes and description of complications.

Several minimally invasive surgical procedures have been proposed as alternative therapies for benign prostatic hyperplasia (BPH). The present systematic review aimed to describe the functional outcomes and complications of emerging minimally invasive transurethral treatments for BPH. A comprehensive bibliographic search on the Medline and Cochrane Library databases was conducted. No chronological restriction was applied. Retrospective and prospective primary studies were included. A meta-analysis of IPSS, IPSS-QoL, Q<inf>max</inf>, and PVR was performed. Data on adverse events were presented narratively. A total of 18 studies were included. Thirteen papers were eligible for the meta-analysis. iTIND (Medi-Tate Ltd., Or-Akiva, Israel), Rezūm (Rezūm System, Boston Scientific, Marlborough, MA), and Aquablation (AquaBeam System, PROCEPT BioRobotics Inc., Redwood City, CA, USA) were associated with a significant improvement in IPSS (P<0.001), IPSS-QoL (P<0.001), and Q<inf>max</inf> (P<0.001) compared to baseline. A significant reduction of PVR from baseline was found with Rezūm (P<0.001) and Aquablation (P<0.001) but not iTIND (P=0.22). A significant difference in IPSS, IPSS-QoL, and Q<inf>max</inf> was shown in favor of Aquablation compared to Rezūm and iTIND (P<0.001). Rezūm and iTIND were mainly associated with mild to moderate adverse effects. Hematuria or bleeding was reported in all studies regarding Aquablation (0.8-26%), the need for transfusion or intervention for bleeding varied between 1.8% and 9%. Aquablation, Rezūm, and iTIND significantly improve urinary functional outcomes compared to baseline; however, Aquablation would seem to lead to better functional results compared to the other procedures. Rezūm and iTIND appear to have an excellent safety profile, while Aquablation would seem to expose patients to a non-negligible risk of bleeding.

Comparative Efficacy and Safety of Diacerein in Patients with Knee Osteoarthritis: A Pilot Study

Background Osteoarthritis (OA) is the most common chronic rheumatic disease. The prevalence of OA is skyrocketing with time. Providing a proper treatment regimen for OA is also growing as a major public health challenge. Conventional pharmacological treatments are mainly for alleviating pain and have some severe adverse effects. Diacerein is a new oral anti-inflammatory drug especially developed for the management of OA having only mild to moderate adverse effects. However, the evidence of efficacy and safety of Diacerein in OA is not well documented and yet to be explored.&#x0D; Objective To compare the efficacy and safety of Diacerein in knee OA with conventional nonsteroidal anti-inflammatory drugs (NSAIDs).&#x0D; Method A comparative study was conducted among knee OA patients attending Out- Patient Orthopedic department in Dhulikhel Hospital, Nepal from December 2019 to September 2020, using self-structured and standard questionnaire. The patients were randomized to receive either a conventional standard treatment (Treatment Group I: NSAIDs) or alternative treatment regimen (Treatment Group II: NSAIDS+ Diacerein). Patients were followed-up after two months and data were analyzed using SPSS 21.0.&#x0D; Result Among 72 patients enrolled in this study, majority (44.44%) were between 51-60 years of age in which 81.94% of the patients were female. Post treatment data was collected from 15 participants. The mean KOOS-PS score of the participants in Treatment Group I decreased from 35.56 ± 14.33 to 35.14 ± 12.65 while that of the Treatment Group II participants reduced from 63.31 ± 12.08 to 49.99 ± 13.10 in two months. Similarly, the mean WOMAC score decreased from 46.87 ± 17.80 to 34.37 ± 16.83 in Treatment Group I and from 54.23 ± 14.66 to 46.22 ± 12.16 in Treatment Group II. The mean Lysholm score in Treatment Group I increased from 55.57 ± 8.16 to 60.86 ± 15.01 and in Treatment Group II, it increased from 46.62 ± 13.01 to 60.25 ± 17.598.&#x0D; Conclusion Diacerein treatment group had better functional outcome compared to the patients in the treatment group with conventionally used drugs. Also, the adverse effects faced by the patients were minor. The current study are suggestive of better efficacy and safety of Diacerein compared to other drugs.

Metabolizing profile of the cytochrome pathway CYP2D6, CYP3A4 and the ABCB 1 transporter in Spanish patients affected by Gaucher disease

Several therapeutic options are available for type 1 Gaucher disease (GD1), including enzymatic replacement therapy (ERT) and substrate reduction therapy (SRT). Eliglustat is a selective inhibitor of glucosylceramide synthase that is extensively metabolized by CYP2D6 and, to a lesser extent by CYP3A4; it is also an inhibitor of the P-gp transporter. The aim of this study is to evaluate the metabolizer profile of these cytochrome isoforms in 61 GD1 patients, and to analyze interferences with concomitant therapies. Patients were selected from the Spanish Gaucher Disease Registry considering clinical data, GBA genotype, severity score index, comorbidities, concomitant drugs, type and response to therapy and adverse effects. The polymorphisms of CYP2D6, CYP3A4 and three ABCB1 transporter variants were analyzed by Polymerase Chain Reaction (PCR). The most frequent metabolizer profile was extensive or intermediate for CYP2D6, extensive for CYP3A4*1B and CYP3A4*22 and normal activity for ABCB1. Correlations between metabolizer profile and other variables were analyzed by multiple regression study. Twenty-eight patients received ERT, 17 eliglustat and seven miglustat. Forty-two patients (68.8%) had associated diseases and 54.5% were taking daily concomitant medication. Nine patients under eliglustat therapy received concomitant drugs that interact with the CYPs and/or ABCB1, five of these did not reach therapeutic goals and three presented mild or moderate adverse effects (headache and gastrointestinal disorders). Detailed analysis in four patients with TTT haplotype, corresponding to lack of activity of the transporter, was performed. In order to apply personalized medicine and avoid interferences and adverse effects, the individual CYP metabolizer profile and transporter must be considered when choosing the concomitant medication and/or making dose adjustments.

Circumcision devices versus standard surgical techniques in adolescent and adult male circumcisions.

Circumcision devices versus standard surgical techniques in adolescent and adult male circumcisions.

Spatial and seasonal variation of trace elements contamination in the sediments of a tropical lagoon ecosystem: the Lake Togo-Lagoon of Aného complex (southern Togo)

The Lake Togo-Lagoon of Aneho complex is located in the area of the phosphorite mining which produces different types of waste that are dumped directly into the surrounding environment without treatment. In addition, the contributions of its tributaries after leaching agricultural and urban soils need to be considered. This increases the risk of contamination of the hydrosystem, especially the sediments in trace elements. The objective of this study is to evaluate the level of trace elements contamination and their spatial and seasonal variation in the sediments of the Lake Togo-Lagoon of Aneho complex. The sediment physicochemical parameters were determined in line with French standards. The trace elements were determined using an Atomic Absorption Spectrometer coupled to a hydride and cold vapour generator. The spatial and seasonal variation was assessed using Ordinary Kriging Interpolation method. The average content of trace elements in sediments in mg/kg was as follow: Cd: 0.75, Pb: 13.26, Cr: 50.63, Ni: 36.05, Cu: 10.90, Hg: 0.04, As: 3.88, Zn: 47.38 and Mn: 766.74 in the dry season. In rainy season, the average concentration was: Cd: 0.46, Pb: 9.50, Cr: 27.43, Ni: 21.36, Cu: 9.61, Hg: 0.05, As: 5.23, Zn: 39.21 and Mn: 910.08. These concentrations showed a strong spatial variation. Significant seasonal variations were obtained for conductivity, organic matter as well as for Cd, Pb, Cr, Ni, Hg and As. The sediments were found to be weakly to moderately contaminated and enriched by trace elements with a higher contamination for Cd. The sediments may have low to moderate adverse effects on aquatic living organisms. This trace element contamination is of anthropogenic origin through the phosphorite mining and the agricultural and urban effluents. Therefore, this lagoon ecosystem warrants regular monitoring for better understanding to inform protection of the resource.

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

Effects of Aloe vera in adults with mucocutaneous problems: A systematic review and meta-analysis.

To analyse the different types of Aloe vera (AV) effects on various mucocutaneous problems among adults. A systematic review and meta-analysis. An exhaustive scanning of PubMed, Medline, ScienceDirect, and Google Scholar databases was conducted from January 2000-December 2019. Randomized controlled trials (RCTs) publishing reports on the effects of AV in various mucocutaneous problems, psoriasis, burn, wound-healing were included. The standardized mean differences (SMD) with 95% confidence Intervals (CIs) were determined for the main outcomes, heterogeneity was analysed using the I2 test and the risk of bias in the studies was reviewed by the Cochrane risk of bias assessment tool. The study included 23 trials with a total of 4,023 participants. Six trials were included in the meta-analysis. The results indicated no significant differences in pain scores as assessed by the Visual Analog Scale (VAS) (SMD=0.11, 95% CI: -0.37 to 0.59). The Psoriasis Area Severity Index (PASI) scores were significantly lower following AV gel application in two of the studies (SMD=-1.32 95% CI: -1.86 to -0.78). Considering results in a systematic manner, AV accelerated tissue epithelialization and wound-healing process (N=3), reduced oral mucositis (N=3), and improved quality of life (N=1). AV might have beneficial effects in reducing pain scores and the severity of mucocutaneous problems compared with placebo, especially with limited mild to moderate adverse effects. AV may be used as an alternative and integrative approach to reducing symptom severity in mucocutaneous problems and the wound-healing process. High quality and well-designed RCTs are still needed to elucidate the effects of AV in a variety of dosages and forms among adults with mucocutaneous problems.

Pregnancy outcomes in women with preexisting thyroid diseases: a French cohort study.

Women with thyroid diseases at the beginning of pregnancy may have suboptimal thyroid hormone levels because of potential difficulties in compensating for the physiological thyroid hormone changes occurring in pregnancy. Our objective was to study the association between preexisting thyroid diseases, pregnancy complications, and neonatal anthropometry. In total, 16,395 women from the ELFE French longitudinal birth cohort were included, and 273 declared pre-pregnancy thyroid diseases. Associations were investigated with multivariable regression models, with adjustment for relevant potential confounders. Body mass index (BMI) was additionally adjusted for in a second stage. As compared with other women, women with pre-pregnancy thyroid diseases were more frequently obese (19.6% vs. 9.8%) and had greater odds of gestational diabetes development (odds ratio [OR] = 1.58 [95% confidence interval [CI] 1.08, 2.30]) or had undergone treatment for infertility (OR = 1.57 [95% CI 1.07, 2.31]). After adjustment for BMI, the association with gestational diabetes was no longer significant (OR = 1.27 [95% CI 0.86, 1.88]). After excluding women with another medical history, those with pre-pregnancy thyroid diseases had increased odds of premature rupture of membranes (OR = 1.51 [95% CI 1.01, 2.25]). Children born from mothers with hypothyroidism before conception due to a disease or as a potential side effect of treatment had a smaller head circumference at birth than other children (β = -0.23 [95% CI -0.44, -0.01] cm). In conclusion, pre-pregnancy thyroid diseases were associated with risk of infertility treatment, gestational diabetes, and premature rupture of membranes. The association between history of hypothyroidism and moderate adverse effects on fetal head circumference growth needs replication.

Vaginal Dilator Utilization in Patients Receiving Curative Radiation for Cancer of the Cervix: A Prospective Study in Botswana

Cervical cancer is the most common malignancy treated with radiation in Botswana and post-treatment dyspareunia and relationship strain is common. To reduce vaginal morbidity following treatment, we introduced a program to offer vaginal dilators in 2017. We sought to assess initial acceptability of vaginal dilators, adherence with use, and barriers to successful use of dilators in a setting with high burden of cervical cancer. Beginning in July 2017, as part of standard clinical care at the sole radiation facility in Botswana, patients with a complete tumor response following curative-intent chemoradiation and brachytherapy, were offered education, a set of vaginal dilators, and lubricant. We analyzed consenting patients in the longitudinal Thabatse Cancer Cohort who received vaginal dilators through December 2019. Patients were reviewed at 6 weeks and thereafter every 3 to 6 months to assess compliance and quality of life. Successful completion of vaginal dilator use was considered as self-reported regular use for 2 years or return to regular sexual activity without dyspareunia. A total of 110 enrolled patients (median Figo stage IIIA) were given dilators. At scheduled 6-week follow-up, 101 (92%) had commenced dilator use. Reasons provided for not starting dilator use were return to regular sexual activity (4), fear of pain (1), fear of bleeding (1), not understanding instructions (1), and no offered reason (2). A successful outcome was observed for 98 (89%)— return to pain-free sexual activity (54, 49%), completed 2 years of use (16, 15%), and continued dilator use (24, 22%). Twelve (11%) women stopped dilator use prior to completion of 2 years. Offered reasons for discontinuing use included: running out of lubricant and pain, bleeding, discomfort with dilator use. Of 58 women returning to sex following treatment for cervical cancer, 50 (86%) were happy with their sex life and 4(7%) reported having pain on sexual intercourse. Reasons offered for not resuming sex were lack/departure of partner, fear of pain, low sexual desire, vaginal dryness, and feeling unwell. During follow up exams, 9 (8%) women provided dilators experienced pain or discomfort on clinical vaginal examination. No moderate or severe adverse effects of dilators were reported. Acceptance of vaginal dilators and self-reported use was high among women completing curative treatment for cervical cancer in Botswana. Further research is needed to optimize patient education and estimate impact of dilator use on function in our population. Retention to dilator use was considerably higher than reported in high-income country contexts and provision of dilators could be especially beneficial in settings like Botswana.

CT Irradiation-induced Changes of Gene Expression within Peripheral Blood Cells.

Computed tomography (CT) is a crucial element of medical imaging diagnostics. The widespread application of this technology has made CT one of the major contributors to medical radiation burden, despite the fact that doses per individual CT scan steadily decrease due to the advancement of technology. Epidemiological risk assessment of CT exposure is hampered by the fact that moderate adverse effects triggered by low doses of CT exposure are likely masked by statistical fluctuations. In light of these limitations, there is need of further insights into the biological processes induced by CT scans to complement the existing knowledge base of risk assessment. This prompted us to investigate the early transcriptomic response of ex vivo irradiated peripheral blood of three healthy individuals. Samples were irradiated employing a modern dual-source-CT-scanner with a tube voltage of 150 kV, resulting in an estimated effective dose of 9.6 mSv. RNA was isolated 1 h and 6 h after exposure, respectively, and subsequently analyzed by RNA deep sequencing. Differential gene expression analysis revealed shared upregulation of AEN, FDXR, and DDB2 6 h after exposure in all three probands. All three genes have previously been discussed as radiation responsive genes and have already been implicated in DNA damage response and cell cycle control after DNA damage. In summary, we substantiated the usefulness of AEN, FDXR, and DDB2 as RNA markers of low dose irradiation. Moreover, the upregulation of genes associated with DNA damage reminds one of the genotoxic nature of CT diagnostics even with the low doses currently applied.

Comparison of daily dosing versus Monday through Friday dosing of vismodegib for locally advanced basal cell carcinoma and basal cell nevus syndrome: A retrospective case series

Comparison of daily dosing versus Monday through Friday dosing of vismodegib for locally advanced basal cell carcinoma and basal cell nevus syndrome: A retrospective case series

3:18 PM Abstract No. 64 Efficacy of prostatic artery embolization for treatment of lower urinary tract symptoms from benign prostatic hyperplasia in the setting of non-obstructive localized prostate cancer

The purpose of this study is to assess clinical outcomes of prostatic artery embolization (PAE) in men with localized prostate cancer (PCa) and lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH). From January 2017 to August 2019, 44 men underwent PAE for LUTS. 10 men (mean age, 70.7; range, 48-85; mean PSA, 13; range, 0.5-37.7; mean Gleason score, 7.3; range, 6-9; 8 undergoing ADT) underwent PAE for LUTS in the setting of non-obstructive PCa. Retrospective review of medical records and imaging studies was performed in order to assess International Prostate Symptom Score (IPSS) (n = 6) and quality of life (QoL) (n = 6) at 12 weeks, cross-sectional prostate volume at 6 weeks (n = 8) and at 12 weeks (n = 6), PSA at 12 weeks (n = 5), and imaging disease progression at 12 weeks (n = 5). PAE was technically successful in all patients. No SIR grade moderate or higher adverse effects were seen. One patient experienced mild adverse effect of bladder spasm. IPSS and QoL at 12 weeks improved by a mean of 11.67 (range, 1-25) and 2.33 (range, 1-24) points, respectively. Mean prostate volume reduction at 6 weeks and 12 weeks was 24.5% (range, 7.2-36.7) and 22.4% (range, -17.9-44), respectively. PSA decreased by average 47% at 12 weeks (range, 1.7-93.3). On 12-week MRI, no lesions increased in PIRADS score, 3 lesions decreased by at least 1 point and no extraprostatic disease progression was seen. All patients completed definitive therapy successfully with prostatectomy (n = 1) or radiation therapy (n = 9). PAE for men with LUTS from BPH and non-obstructive PCa results in clinical improvement without increased side effects of non-target embolization or disease progression. PAE is safe and effective for men with LUTS from BPH in the setting of non-obstructive PCa.

Sofosbuvir: Really Meets the Unmet Needs for Hepatitis C Treatment?

Chronic hepatitis C remains a major public health concern with a prevalence of more than 1% worldwide. Of late, with the discovery of newer drugs, chronic HCV treatment has touched new dimensions. The treatment has progressed from Interferons to Pegylated interferon (Peg IFN) based therapy, with or without ribavirin to treatment with orally active Direct Acting Antivirals (DAA) with Peg IFN and ribavirin and eventually to various combinations of DAA, without IFN. Introduction of newer DAAs has transfigured the treatment of chronic HCV. Chronic HCV patients with advanced liver disease, psychiatric condition, anemia or autoimmune diseases, not eligible for Peg IFN based therapy have a ray of hope now. Amongst all DAAs, nucleoside inhibitors have been the most promising agent. Thus the present review focuses on Sofosbuvir, one of the most effective nucleoside inhibitors; in terms of potency, resistance profile, activity against all genotypes of HCV and adverse effects. FDA approved Sofobuvir for clinical use in 2013. Chemically, it is 2'-deoxy-2'-α-fluoro-β-Cmethyluridine- 5'-triphosphate; a phosphoramidate prodrug that is activated by enzyme present in human liver. It is a highly potent inhibitor of HCV NS5B polymerase. Efficacy of the Sofosbuvir has been established in various phase 2 and phase 3 clinical trials like PROTON, ELECTRON, FUSION, POSITRON etc. Sofosbuvir has a good safety profile with few mild to moderate adverse effects. Evidence reveals that sofosbuvir has substantial impact on the treatment of HCV.

Mechanical properties of discrete BFRP needles reinforced seawater sea-sand concrete-filled GFRP tubular stub columns

This paper proposes a new type of tubular column, which is composed of glass fiber-reinforced polymer (GFRP) tube and discrete basalt fiber-reinforced polymer (BFRP) needles reinforced seawater sea-sand concrete (SWSSC). The discrete BFRP needles, with an aspect ratio of 10.0, were cut from BFRP bar production scrap and mixed into fresh concrete to replace 20% of the coarse aggregates by volume. The axial compression properties and lateral bending properties of the tubular columns were tested. The test variables included the wall thickness of the GFRP tubes (i.e., 3 mm and 4 mm), the type of coarse aggregates (i.e., gravel or coral), and the incorporation of BFRP needles or not. Additionally, unconfined bare columns were tested for comparison. The test results showed that the inclusion of BFRP needles had moderate adverse effects on the peak compressive strength of bare columns: the peak axial stress reduced slightly by 2.5% for gravel concrete and 7.2% for coral concrete, respectively. Besides, for the four types of concrete in this paper, the 3- and 4-mm GFRP tube-confinement increased the peak axial compressive strengths by 23 ~ 52% and 65 ~ 83%, respectively. In addition, the adoption of GFRP tubes was able to improve the bending performance of columns significantly, especially for energy consumption.

Aggregate and Intergenerational Implications of School Closures: A Quantitative Assessment

A majority of governments around the world unprecedentedly closed schools in response to the COVID-19 pandemic. This paper quantitatively investigates the macroeconomic and distributional consequences of school closures through intergenerational channels in the medium-and long-term. The model economy is a dynastic overlapping generations general equilibrium model in which schools, in the form of public education investments, complement parental investments in producing children’s human capital. We calibrate the stationary equilibrium of the model to the U.S. economy and compute the equilibrium responses following unexpected school closure shocks. We find that school closures have moderate long-lasting adverse effects on macroeconomic aggregates such as output. The accumulated output loss over the next century relative to the annual output, following a half-year-long closure, exceeds 5%. In addition, we find that school closures reduce intergenerational mobility, especially among older children. Finally, we find that lower substitutability between public and parental investments induces larger damages in the aggregate economy and overall lifetime incomes of the affected children while mitigating negative impacts on intergenerational mobility. In all findings, heterogeneous parental responses to school closures play a key role. Our results provide a quantitatively relevant dimension to consider for policymakers assessing potential costs of school closures.

Intravenous iron therapy for non-anaemic, iron-deficient adults.

Iron deficiency is one of the most common nutritional deficiencies, and has a number of physiological manifestations. Early, or non-anaemic iron deficiency can result in fatigue and diminished exercise capacity. Oral iron preparations have a high incidence of intolerable side effects, and are ineffective in certain forms of iron deficiency. Consequently, intravenous iron preparations are increasingly used in the treatment of non-anaemic iron deficiency. The newer, more stable iron preparations in particular purport to have a lower incidence of side effects, and are now used across a range of different patient populations. To assess the effects of intravenous iron therapy in the treatment of adults with non-anaemic iron deficiency. On 18 October 2019 we electronically searched CENTRAL, MEDLINE, Embase, two further databases and two trials registries 2019. We handsearched the references of full-text extracted studies, and contacted relevant study authors for additional data. We included randomised controlled trials that compared any intravenous iron preparation to placebo in adults. We excluded other forms of comparison such as oral iron versus placebo, intramuscular iron versus placebo, or intravenous iron studies where other iron preparations were used as the comparator. We also excluded studies involving erythropoietin therapy or obstetric populations. Two review authors screened references for eligibility, extracted data and assessed risk of bias. We resolved differences in opinion through discussion and consensus, and where necessary, involved a third review author to adjudicate disputes. We contacted study authors to request additional data where appropriate. The primary outcome measures were haemoglobin concentration at the end of follow-up, and quality-of-life scores at end of follow-up. Secondary outcome measures were serum ferritin, peak oxygen consumption (as measured by cardiopulmonary exercise testing), adverse effects (graded as mild to moderate and severe) and bacterial infection. We pooled data for continuous outcomes, which we then reported as mean differences (MDs) with 95% confidence intervals (CIs). We reported quality-of-life metrics as standardised mean difference (SMD), and then converted them back into a more familiar measure, the Piper Fatigue Scale. We analysed dichotomous outcomes as risk ratios (RRs). Given an expected degree of heterogeneity, we used a random-effects model for all outcomes. We performed the analysis with the software package Review Manager 5. This review includes 11 studies with 1074 participants. Outcome metrics for which data were available (haemoglobin concentration, quality-of-life scores, serum ferritin, peak oxygen consumption and mild to moderate adverse effects) were similar across the included studies. The incidence of severe adverse events across all studies was zero. None of the studies measured bacterial infection as a specific outcome metric. Substantial heterogeneity influenced the results of the meta-analysis, arising from differing patient populations, definitions of iron deficiency, iron preparations and dosing regimens, and time to end of follow-up. Consequently, many outcomes are reported with small group sizes and wide confidence intervals, with a subsequent downgrading in the quality of evidence. The level of bias in many included studies was high, further reducing confidence in the robustness of the results. We found that intravenous iron therapy may lead to a small increase in haemoglobin concentration of limited clinical significance compared to placebo (MD 3.04 g/L, 95% CI 0.65 to 5.42; I2 = 42%; 8 studies, 548 participants; low-quality evidence). Quality-of-life scores (Piper Fatigue Scale MD 0.73, 95% CI 0.29 to 1.18; I2 = 0%; studies = 3) and peak oxygen consumption (MD 2.77 mL/kg/min, 95% CI -0.89 to 6.43; I2 = 36%; 2 studies, 32 participants) were associated with very low-quality evidence, and we remain uncertain about the role of intravenous iron for these metrics. We were unable to present pooled estimates for the outcomes of serum ferritin at the end of follow-up or mild to moderate adverse effects due to extreme statistical heterogeneity. Ultimately, despite the results of the meta-analysis, the low- or very low-quality evidence for all outcomes precludes any meaningful interpretation of results beyond suggesting that further research is needed. We performed a Trial Sequential Analysis for all major outcomes, none of which could be said to have reached a necessary effect size. Current evidence is insufficient to show benefit of intravenous iron preparations for the treatment of non-anaemic iron deficiency across a variety of patient populations, beyond stating that it may result in a small, clinically insignificant increase in haemoglobin concentration. However, the certainty for even this outcome remains limited. Robust data for the effectiveness of intravenous iron for non-anaemic iron deficiency is still lacking, and larger studies are required to assess the effect of this therapy on laboratory, patient-centric, and adverse-effect outcomes.

Pre-Existing Comorbid Emotional Symptoms Moderate Short-Term Methylphenidate Adverse Effects in a Randomized Trial of Children with Attention-Deficit/Hyperactivity Disorder.

Objective: We sought to ascertain whether baseline anxiety/depression and oppositional defiant disorder (ODD) symptoms impacted the experience of short-term methylphenidate (MPH) adverse effects (AEs) in 7- to 11-year-old children with attention-deficit/hyperactivity disorder (ADHD) (n = 171) undergoing a double-blind MPH crossover trial. Method: The Vanderbilt ADHD Diagnostic Parent Rating Scale measured baseline child anxiety/depression and ODD symptomology. The parent-completed Pittsburgh Side Effect Rating Scale assessed the AEs of anxiety, sadness, and irritability at baseline, on placebo, and on three MPH dosages. For each AE, we evaluated comorbidity main effects, dose main effects, and comorbidity × dose interactions. Results: Baseline anxiety/depression × dose and ODD × dose interactions were significant for the AEs of anxiety, sadness, and irritability. Compared with premedication baseline, these AEs attenuated on MPH for children with initially higher comorbidity symptoms, whereas those with initially lower comorbidity symptoms tended toward no change or increasing AE levels. Conclusion: Premedication anxiety/depressive and ODD symptoms may be important predictors of short-term MPH emotional AEs.

Adaptation to climate change in coastal communities: findings from seven sites on four continents

Climate change is causing wide-ranging effects on ecosystem services critical to coastal communities and livelihoods, creating an urgent need to adapt. Most studies of climate change adaptation consist of narrative descriptions of individual cases or global synthesis, making it difficult to formulate and test locally rooted but generalizable hypotheses about adaptation processes. In contrast, researchers in this study analyzed key points in climate change adaptation derived from coordinated fieldwork in seven coastal communities around the world, including Arctic, temperate, and tropical areas on four continents. Study communities faced multiple challenges from sea level rise and warmer ocean temperatures, including coastal erosion, increasing salinity, and ecological changes. We analyzed how the communities adapted to climate effects and other co-occurring forces for change, focusing on most important changes to local livelihoods and societies, and barriers to and enablers of adaptation. Although many factors contributed to adaptation, communities with strong self-organized local institutions appeared better able to adapt without substantial loss of well-being than communities where these institutions were weak or absent. Key features of these institutions included setting and enforcing rules locally and communication across scales. Self-governing local institutions have been associated with sustainable management of natural resources. In our study communities, analogous institutions played a similar role to moderate adverse effects from climate-driven environmental change. The findings suggest that policies to strengthen, recognize, and accommodate local institutions could improve adaptation outcomes.