Effectiveness of a monthly schedule of follow-up for the treatment of uncomplicated severe acute malnutrition in Sokoto,Nigeria: A cluster randomized crossover trial

BackgroundCommunity-based management of severe acute malnutrition (SAM) involves weekly or biweekly outpatient clinic visits for clinical surveillance and distribution of therapeutic foods. Distance to outpatient clinics and high opportunity costs for caregivers can represent major barriers to access. Reducing the frequency of outpatient visits while providing training to caregivers to recognize clinical danger signs at home between outpatient visits may increase acceptability, coverage, and public health impact of SAM treatment. We investigated the effectiveness of monthly clinic visits compared to the standard weekly follow-up in the outpatient treatment of uncomplicated SAM in northwestern Nigeria.Methods and findingsWe conducted a cluster randomized crossover trial to test the noninferiority of nutritional recovery in children with uncomplicated SAM receiving monthly follow-up compared to the standard weekly schedule. From January 2018 to November 2019, 3,945 children aged 6 to 59 months were enrolled at 10 health centers (5 assigned to monthly follow-up and 5 assigned to weekly follow-up) in Sokoto, Nigeria. In total, 96% of children (n = 1,976 in the monthly follow-up group and 1,802 in the weekly follow-up group) were followed until program discharge, and 91% (n = 1,873 in the monthly follow-up group and 1,721 in the weekly follow-up group) were followed to 3 months postdischarge. The mean age at admission was 15.8 months (standard deviation [SD] 7.1), 2,097/3,945 (53.2%) were girls, and the mean midupper arm circumference (MUAC) at admission was 105.8 mm (SD 6.0). In a modified intention-to-treat analysis, the primary outcome of nutritional recovery, defined as having MUAC ≥125 mm on 2 consecutive visits, was analyzed using generalized linear models, with generalized estimating equations to account for clustering. Nutritional recovery was lower in the monthly follow-up group compared to the weekly group (1,036/1,976, 52.4% versus 1,059/1,802, 58.8%; risk difference: −6.8%), and noninferiority was not demonstrated (lower bound of the confidence interval [CI] was −11.5%, lower than the noninferiority margin of 10%). The proportion of children defaulting was lower in the monthly group than in the weekly group (109/1,976, 5.5% versus 151/1,802, 8.4%, p = 0.03). Three months postdischarge, children in the monthly group were less likely to relapse compared to those in the weekly group (58/976, 5.9% versus 78/1,005, 7.8%, p = 0.03), but cumulative mortality at 3 months postdischarge was higher in the monthly group (159/1,873, 8.5% versus 106/1,721, 6.2%, p < 0.001). Study results may depend on context-specific factors including baseline level of care and the clinical status of children presenting to health centers, and, thus, generalizability of these results may be limited.ConclusionsWhere feasible, a weekly schedule of clinic visits should be preferred to maintain effectiveness of SAM treatment. Where geographic coverage of programs is low or frequent travel to outpatient clinics is difficult or impossible, a monthly schedule of visits may provide an alternative model to deliver treatment to those in need. Modifications to the outpatient follow-up schedule, for example, weekly clinic visits until initial weight gain has been achieved followed by monthly visits, could increase the effectiveness of the model and add flexibility for program delivery.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03140904","term_id":"NCT03140904"}}NCT03140904.

Matt D.T. Hitchings and colleagues investigate the effectiveness of a monthly schedule of follow-up for the management of uncomplicated severe acute malnutrition in children aged 6-59 months in Nigeria.     

Characterising deviation from treat-to-target strategies for early rheumatoid arthritis: the first three years

IntroductionTreat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow.MethodsIn this retrospective cohort study, treatment-naïve patients with RA of less than one year’s duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis.ResultsIn total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P <0.0001). On multivariate analysis, only body mass index (P = 0.003) and helplessness score (P = 0.04) were independent predictors of protocol deviations although the predictive power of the model was not strong (R² = 0.17).ConclusionsDeviation from a T2T protocol occurred in one quarter of visits, indicating that applying the T2T approach is feasible in clinical practice. Failure to escalate dose when indicated was commonly encountered, and just under half of the observed deviations were related to either toxicities or comorbidities and were therefore justifiable on clinical grounds.     

Assessing clinicians’ Post-Exposure Prophylaxis recommendations for rabies virus exposures in Hunan Province,China

BackgroundTimely and appropriate administration of post-exposure prophylaxis (PEP) is an essential component of human rabies prevention programs. We evaluated patient care at rabies clinics in a high-risk county in Hunan Province, China to inform strategies needed to achieve dog-mediated human rabies elimination by 2030.MethodsWe collected information on PEP, staff capacity, and service availability at the 17 rabies clinics in the high-risk county during onsite visits and key staff interviews. Additionally, we conducted observational assessments at five of these clinics, identified through purposive sampling to capture real-time information on patient care during a four-week period. Wound categories assigned by trained observers were considered accurate per national guidelines for comparison purposes. We used the kappa statistic and an alpha level of 0.05 to assess agreement between observers and clinic staff.ResultsIn 2015, the 17 clinics provided PEP to 5,261 patients. Although rabies vaccines were available at all 17 clinics, rabies immune globulin (RIG) was only available at the single urban clinic in the county. During the assessment period in 2016, 196 patients sought care for possible rabies virus exposures. According to observers, 88 (44%) patients had category III wounds, 104 (53%) had category II wounds and 4 (2%) had category I wounds. Observers and PEP clinic staff agreed on approximately half of the assigned wound categories (kappa = 0.55, p-value< 0.001). Agreement for the urban county-level CDC clinic (kappa = 0.93, p-value<0.001) was higher than for the township clinics (kappa = 0.16, p-value = 0.007). Using observer assigned wound categories, 142 (73%) patients received rabies vaccinations and RIG as outlined in the national guidelines.ConclusionRabies PEP services were available at each town of the project county; however, gaps between clinical practice and national rabies guidelines on the use of PEP were identified. We used these findings to develop and implement a training to rabies clinic staff on wound categorization, wound care, and appropriate use of PEP. Additional risk-based approaches for evaluating human rabies virus exposures may be needed as China progresses towards elimination.     

Weather, Water Quality and Infectious Gastrointestinal Illness in Two Inuit Communities in Nunatsiavut, Canada: Potential Implications for Climate Change

Climate change is expected to cause changes in precipitation quantity, intensity, frequency and duration, which will subsequently alter environmental conditions and might increase the risk of waterborne disease. The objective of this study was to describe the seasonality of and explore associations between weather, water quality and occurrence of infectious gastrointestinal illnesses (IGI) in two communities in Nunatsiavut, Canada. Weather data were obtained from meteorological stations in Nain (2005–2008) and Rigolet (2008). Free-chlorine residual levels in drinking water were extracted from municipal records (2005–2008). Raw surface water was tested weekly for total coliform and E. coli counts. Daily counts of IGI-related clinic visits were obtained from health clinic registries (2005–2008). Analysis of weather and health variables included seasonal-trend decomposition procedures based on Loess. Multivariable zero-inflated Poisson regression was used to examine potential associations between weather events (considering 0–4 week lag periods) and IGI-related clinic visits. In Nain, water volume input (rainfall + snowmelt) peaked in spring and summer and was positively associated with levels of raw water bacteriological variables. The number of IGI-related clinic visits peaked in the summer and fall months. Significant positive associations were observed between high levels of water volume input 2 and 4 weeks prior, and IGI-related clinic visits (P < 0.05). This study is the first to systematically gather, analyse and compare baseline data on weather, water quality and health in Nunatsiavut, and illustrates the need for high quality temporal baseline information to allow for detection of future impacts of climate change on regional Inuit human and environmental health.     

Twenty Years of Medically-Attended Pediatric Varicella and Herpes Zoster in Ontario,Canada: A Population-Based Study

ObjectiveTo determine if reductions in medically-attended pediatric varicella and herpes zoster occurred in Ontario, Canada, after publicly-funded varicella immunization was implemented in 2004.MethodsFor fiscal years (FY) 1992-2011, we examined data on varicella and herpes zoster physician office visits, emergency department (ED) visits, hospitalizations (including for varicella-associated skin and soft tissue infections [SSTI]), and intensive care unit (ICU) admissions, among those aged <18 years. The pre-vaccine, privately-available, and vaccine program eras were FY1992-1998, FY1999-2003, and FY2004-2011, respectively. We used Poisson regressionand Kruskal-Wallis tests (all at the p<0.05 level of significance), and compared rates using incidence rate ratios (IRRs) and 95% confidence intervals (CIs).ResultsIncidence of varicella office visits declined over the study period from a high of 25.1/1,000 in FY1994 to a low of 3.2/1,000 in FY2011. ED visits and hospitalizations followed similar patterns of decreasing rates later in the study period. IRRs comparing the vaccine program versus pre-vaccine eras were 0.29 (95%CI: 0.26-0.32) for office visits, 0.29 (95%CI: 0.21-0.40) for ED visits, and 0.41 (95%CI: 0.10-1.69) for hospitalizations. Annual declines in varicella office visits were 7.7%, 9.1%, 8.4%, and 8.4% per year among children aged <1 year, 1-4 years, 5-11 years, and ≥12 years, respectively (all p<0.001). Age-specific rates of varicella-associated SSTI declined significantly among children <12 years (p<0.001) and rates of ICU admissions decreased significantly for children <1 year (p = 0.02). (p<0.001) over the study period. For children aged 5-17 years, herpes zoster office visits decreased whereas ED visits increased (both p<0.001) and there was a small, non-significant (p = 0.07), decrease in hospitalizations.ConclusionMedically-attended varicella decreased during the study period, particularly since varicella vaccine was publicly-funded. Results suggest immunization program-related changes in varicella epidemiology, including herd effects, demonstrated by reductions in varicella in program-ineligible age groups. We did not observe a consistent impact on herpes zoster.     

Childhood brain tumours,early infections and immune stimulation: A pooled analysis of the ESCALE and ESTELLE case-control studies (SFCE,France)

BackgroundFew studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals.MethodsWe pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders.ResultsThe analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7–1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7–1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56–1.1). Farm visits (OR: 0.6, 95%CI: 0.5–0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6–1.0) in the first year of life were inversely associated with CBT.ConclusionsOur findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation.     

A Low-Cost Ultrasound Program Leads to Increased Antenatal Clinic Visits and Attended Deliveries at a Health Care Clinic in Rural Uganda

Background

In June of 2010, an antenatal ultrasound program to perform basic screening for high-risk pregnancies was introduced at a community health care center in rural Uganda. Whether the addition of ultrasound scanning to antenatal visits at the health center would encourage or discourage potential patients was unknown. Our study sought to evaluate trends in the numbers of antenatal visits and deliveries at the clinic, pre- and post-introduction of antenatal ultrasound to determine what effect the presence of ultrasound at the clinic had on these metrics.

Methods and Findings

Records at Nawanyago clinic were reviewed to obtain the number of antenatal visits and deliveries for the 42 months preceding the introduction of ultrasound and the 23 months following. The monthly mean deliveries and antenatal visits by category (first visit through fourth return visit) were compared pre- and post- ultrasound using a Kruskal-Wallis one-way ANOVA. Following the introduction of ultrasound, significant increases were seen in the number of mean monthly deliveries and antenatal visits. The mean number of monthly deliveries at the clinic increased by 17.0 (13.3–20.6, 95% CI) from a pre-ultrasound average of 28.4 to a post-ultrasound monthly average of 45.4. The number of deliveries at a comparison clinic remained flat over this same time period. The monthly mean number of antenatal visits increased by 97.4 (83.3–111.5, 95% CI) from a baseline monthly average of 133.5 to a post-ultrasound monthly mean of 231.0, with increases seen in all categories of antenatal visits.

Conclusions

The availability of a low-cost antenatal ultrasound program may assist progress towards Millennium Development Goal 5 by encouraging women in a rural environment to come to a health care facility for skilled antenatal care and delivery assistance instead of utilizing more traditional methods.     

Burden of Illness,Annual Healthcare Utilization,and Costs Associated with Commercially Insured Patients with Cushing Disease in The United States

ObjectiveTo describe the burden of illness, healthcare utilization, and costs associated with Cushing disease (CD), a rare disorder resulting from adrenocorticotropic hormone-secreting pituitary tumors, in commercially insured patients in the U.S.MethodsPatients with CD were identified in 2010 in the IMS Health PharMetrics and Truven Health Analytics MarketScan claims databases. Because there is no diagnosis code for CD, patients were identified with a claim for Cushing syndrome and either benign pituitary adenoma or hypophysectomy. We estimated total sand CD-related utilization and costs using pharmacy and medical claims.ResultsWe identified 685 CD patients (81% female; mean age, 41.7 years; mean Charlson comorbidity index, 1.6; mean number of chronic conditions, 4.2); 30.5% of the patients had diabetes, 22.5% had psychiatric disturbances, 21% had infections, 8.6% had osteoporosis, 8% had cardiovascular disease/stroke, 5.5% had kidney stones, and 0.7% had compression fracture of a vertebra. Patients had a mean of 19.8 office visits per year; 38.4% had inpatient hospitalizations and 34.2% visited the emergency department (ED). Patients had a mean of 3.2 CD-related office visits per year; 26.9% had CD-related hospitalizations, 0.9% had CD-related ED visits, and 36.8% had CD treatments. Mean annual total costs were $34,992 (pharmacy, $3,597; medical costs, $31,395). CD-related costs accounted for $14,310 of total costs (CD treatment costs, $9,353; other CD-related costs, $4,957).ConclusionCD patients have a high burden of illness. Among CD patients in this study, 30.5% had diabetes, 22.5% had psychiatric disturbances, 21% had infections, 8.6% had osteoporosis, 8% had cardiovascular disease/ stroke, and 5.5% had kidney stones. Patients had 19.8 office visits per year, and > 34% of patients were hospitalized. Mean total cost of care was approximately $35,000 per year. (Endocr Pract. 2015;21:77-86)     

Telemedicine for Hip Preservation Patients: Access,Ability and Preference

BackgroundRecent events have resulted in rapid rises in the use of telemedicine in orthopaedic surgery, despite limited evidence regarding patient preferences or concerns. The purpose of this study is to determine access to and, ability to use telemedicine technology in an adult hip preservation patient population, as well as determine associations with patient characteristics. Additionally, we seek to understand patients’ perceived benefits, risks and preferences of telemedicine.MethodsWe performed a cross-sectional survey administered on patients scheduled to undergo joint preservation surgery by one of three surgeons at a single academic institution. Both preoperative and postoperative established patients were included and called for a telephone administered survey if a date of surgery was scheduled between October 1, 2019 and March 30, 2020 and were 18 years or older. The survey had seven sections with 45 questions relating to demographics, technology access, videoconferencing capability, confidence using technology, telehealth experiences, perceptions.Results101 patients completed the survey (48% response rate, 101/212). Overall, 99% of participants reported using the internet, 94% reporting owning a device capable of videoconferencing, and 86% of patients had participated in a video call in the past year. When asked for their preferred method for a physician visit: 79% ranked in-person as their first choice and 16% ranked a videoconference visit as their first choice. Perceived benefits of telemedicine visits included reduced travel to appointments (97% agree) and reduced cost of attending appointments (69% agree). However, patients were concerned that they would not establish the same patient-physician connection (51% agree) and would not receive the same level of care (38% agree) through telemedicine visits versus in person visits.ConclusionThe majority of hip preservation patients have access to and are capable of using the technology required for telemedicine visits. However, patients still prefer to have in person visits over concerns that they will not establish the same patient-physician connection and will not receive the same level of care. Telemedicine visits in hip preservation patients may be most attractive to return patients with an established doctor-patient relationship, particularly those with concerns for long distances of travel and associated costs.Level of Evidence: III     

The influence of survey frequency on population estimates of moorland breeding birds

Capsule A minimum of four constant‐effort‐search survey visits are required to generate reliable population estimates of breeding birds on moorland that are not subject to biases associated with varying levels of detectability through the season.

Aims To investigate the influence of the number and the combination of survey visits on the population estimates of breeding birds on moorland.

Methods Four constant‐effort‐search surveys (80–100 minutes per km² per visit) of moorland in southwest Scotland were undertaken in each of six years, 2003–2008. Using standard protocols, the numbers of apparent territories that would have been identified for each possible combination of survey visits were determined.glms were used to assess the influence of the frequency of survey visits, and different combination scenarios on the derived population estimates for Red Grouse, European Golden Plover, Common Snipe, Eurasian Curlew, Sky Lark, Winter Wren and Stonechat. Independent assessments of population density were made by transect sampling for Red Grouse and Sky Lark.

Results Robust population estimates were possible from three survey visits for European Golden Plover, Eurasian Curlew and Stonechat. However, there were differences between species in the seasonal variation of their detectability. Four survey visits would underestimate the populations of Red Grouse (probably by 67–91%), Sky Lark (probably by 31–61%) and Winter Wren (by an undetermined proportion). Common Snipe were also likely to be underestimated after four survey visits, but the value of the derived estimate as an index of population density deserves further investigation.

Conclusions If there is a need to carry out a multi‐species survey on moorland, we suggest that a minimum of four survey visits is required to ensure the derivation of reliable population estimates for a suite of the most readily detectable species. Population estimates derived from three or fewer survey visits risk biases through uneven sampling in periods of differing detectability. With evidence for changes in the breeding phenology of birds associated with changing climate or weather patterns, it arguably becomes more important to ensure that surveys sample an adequately broad period of the breeding season.     

Telehealth for Endocrinology: Experience and Effect on Utilization in the Prepandemic Era

ObjectiveTelehealth (TH) use in endocrinology was limited before the COVID-19 pandemic but will remain a major modality of care postpandemic. Reimbursement policies have been limited historically due to concerns of overutilization of visits and testing. Additionally, there is limited literature on endocrinology care delivered via TH for conditions other than diabetes. We assess real-world TH use for endocrinology in a prepandemic environment with the hypothesis that TH would not increase the utilization of total visits or related ancillary testing services compared with conventional (CVL) face-to-face office visits.MethodsA single-institution retrospective cohort study assessing the prepandemic use of TH in endocrinology, consisting of 75 patients seen via TH and 225 patients seen in CVL visits. For most patients, TH was conducted via a clinic-to-clinic model. Outcomes measured were total endocrine visit frequency and frequency of related laboratory and radiology testing per patient, hemoglobin A1C, microalbumin, low-density lipoprotein, thyroid-stimulating hormone, thyroglobulin, and thyroid ultrasounds.ResultsFor all endocrine visits, TH patients had a median of 0.24 (interquartile range, 0.015-0.36) visits per month. CVL patients had a median of 0.20 visits per month (interquartile range, 0.11-0.37). Total visits per month did not vary significantly between groups (P = .051). Hemoglobin A1C outcomes were equivalent and there was no increase in ancillary laboratory testing for the TH group.ConclusionOur observations demonstrate that, in a prepandemic health care setting, TH visits can provide equivalent care for endocrinology patients, without increasing utilization of total visits or ancillary services.     

Open-label,multi-center,non-randomized,single-arm study to evaluate the safety and efficacy of dendritic cell immunotherapy in patients with refractory solid malignancies,on supportive care

Background aimsA phase II clinical trial of an autologous dendritic cell (DC) formulation for the management of refractory solid malignant tumors was conducted across six sites in India with an objective to study safety and efficacy.MethodsA total of 51 patients with refractory cancer (either sex) with life expectancy ≥3 months, Eastern Cooperative Oncology Group score ≤2, available tumor tissue and adequate organ and bone marrow function were recruited. Monocytes obtained by leukapheresis, differentiated into DCs by cytokines and primed with autologous tumor lysate (fresh tissue biopsy or paraffin block). On the 8th day, mature DCs were analyzed for expression of CD40, CD80, CD83, CD86, DC205 and DC209. The treatment regime consisted of six doses (intravenous) over 14 weeks with 2 post-treatment follow-up visits, 6 weeks apart. Safety was assessed at all visits and responses were evaluated on days 58, 100 and 184 or at end of the study.ResultsA total of 38 patients were evaluated for safety and efficacy. One adverse event classified as possibly related was an episode of rigors or chills with mild pyrexia during one infusion. Objective response rate by Response Evaluation Criteria In Solid Tumors was 28.9% (11/38) and immune-related response criteria was 42.1% (16/38); 90% confidence interval for objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation Criteria In Solid Tumors and immune-related response criteria, respectively. The median time to treatment progression was >9 weeks. Median overall survival was 397 days. An increase in the expression of interferon-γ was not significant.ConclusionsTherapy was safe. The responses, time to treatment progression and survival are encouraging for patients with aggressive refractory disease.     

Association between exercise habits and stroke,heart failure,and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study

BackgroundThere is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death.Methods and findingsThis is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90–0.99) and 0.92 (0.88–0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73–0.91) for new exercisers, 0.83 (0.74–0.93) for exercise dropouts, and 0.61 (0.55–0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%–14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000–1,499 MET-min/wk (regular moderate exercise 170–240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups.ConclusionsInitiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.

Using a population-based cohort study, Dr. Choi and colleagues studied patients with atrial fibrillation to determine whether their exercise habits were associated with occurrence of ischemic stroke, heart failure, and all-cause mortality.     

Value of Baseline Serum Thyrotropin as a Predictor of Hypothyroidism in Patients With Diabetes Mellitus

ObjectiveTo determine whether serum thyrotropin measurement performed at diagnosis of diabetes mellitus or at initial patient contact predicts subsequent development of hypothyroidism.MethodsWe retrospectively reviewed the computerized records of patients attending annual visits between January 2008 and December 2008 at a hospital diabetes mellitus clinic. Serum free thyroxine and thyrotropin at current and baseline annual visits were documented. A Cox regression model was used to analyze the relationship between development of thyroid dysfunction and patient characteristics including age, sex, type of diabetes, and baseline serum thyrotropin concentration. KaplanMeier survival curves were generated for predictors of hypothyroidism.ResultsClinical records of 1101 patients were reviewed (595 men [54%] and 506 women [46%]). Mean age was 60.0 ± 17 years. Two hundred twenty-three patients (20.3%) had type 1 DM and 878 (79.7%) had type 2 diabetes. Thyroid dysfunction was present in 136 patients (12.4%) at baseline and developed in 71 patients (6.4%) at follow-up (median duration, 37 months). Overt and subclinical hypothyroidism developed in 28 (2.5%) and 38 (3.5%) patients, respectively. Incident hypothyroidism was associated with baseline thyrotropin concentration greater than 2.2 mIU/L (relative risk, 10.4; confidence interval, 5.6-19.6; P < .001) and female sex (relative risk, 1.8; confidence interval, 1.1-2.9; P = .007). The predictive influence of sex was abolished in patients with a thyrotropin value greater than 2.2 mIU/L. This TSH threshold yielded an optimal sensitivity and specificity of 83% and 72%, respectively, for predicting hypothyroidism.ConclusionsBaseline serum thyrotropin predicted hypothyroidism in patients with diabetes mellitus even at thyrotropin concentrations within the reference range. Selective annual thyroid screening in diabetic patients with baseline thyrotropin concentrations greater than 2.2 mIU/L may be more cost-effective than universal screening. (Endocr Pract. 2011;17:26-32)     

Beyond Body Mass Index - Body Composition Assessment by Bioimpedance in Routine Endocrine Practice

ObjectiveTo explore the body composition of pediatric patients referred for endocrine evaluation.MethodsThis real-life observational study conducted between January 2018 and January 2020 included 10 001 clinic visits of 3500 children and adolescents; first visits of 5 to 18-year-old patients were included. Anthropometric data, blood pressure levels, pubertal status, and bioelectrical impedance analysis (BIA, Tanita MC-780 MA) were extracted from medical files. Excluded from the analysis were patients participating in other studies.ResultsA total of 1001 patients (48% boys, mean age 11.3 ± 3.4 years, 33.5% prepubertal) were included. Mean anthropometric z-scores were normal and similar for boys and girls. Sex differences in body composition were as follows: boys had lower fat percentage, lower truncal fat percentage, higher appendicular skeletal muscle mass, and a higher muscle-to-fat ratio (MFR) than girls (P < .001 for all). MFR correlated with body mass index-standard deviation scores (BMI-SDS) in overweight/obese patients (r = −0.558, P < .001), although not in underweight patients. Systolic blood pressure (SBP) correlated with BMI-SDS in overweight/obese patients (r = 0.262, P < .001), although not in underweight patients. Diastolic blood pressure (DBP) did not correlate with BMI-SDS in either group of extreme weight status. MFR correlated with SBP and DBP in overweight/obese patients (r = −0.230, P < .001 and r = −0.141, P = .018, respectively) as well as in underweight patients (r = 0.331, P < .001 and r = 0.264, P = .005, respectively).ConclusionsOur findings support BIA for a more refined characterization of patients referred for endocrine evaluation than BMI-SDS. MFR may be a better surrogate marker of blood pressure levels than BMI-SDS in both underweight and overweight/obese pediatric patients.     

Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review

ObjectiveTo compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.DesignSystematic review of randomised trials comparing low dosage tricyclics (⩽100 mg/day) with placebo or with standard dosage tricyclics in adults with depression.Results35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.ConclusionsTreatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of various dosages.

What is already known on this topic

Tricyclics are still prescribed as often as selective serotonin reuptake inhibitors and other newer antidepressants worldwideExperts have often claimed that clinicians prescribe tricyclics at less than adequate dosages

What this study adds

Tricyclics at dosages below the recommended range are more effective than placeboThey may or may not be as effective as standard dosage tricyclics but result in fewer dropouts due to side effectsThe minimum effective dosage and ranges for antidepressants has not been established—a simple set of numbers that every practising doctor and patient would want to know     

Effect of Spironolactone Therapy on Albuminuria in Patients with Type 2 Diabetes Treated with Angiotensin-Converting Enzyme Inhibitors

ObjectiveTo investigate whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors further decreases albuminuria in patients with type 2 diabetes mellitus (DM).MethodsWe conducted a prospective open-label trial in patients recruited at the Cleveland Clinic between February 2004 and November 2006. Patients with type 2 DM were eligible if they were older than 18 years of age, had been treated with any ACE inhibitor for longer than 1 month, and had a random urinary albumin to creatinine ratio (ACR) greater than 100 mg/g within 1 month of study entry. Based on screening ACR, patients were assigned to a microalbuminuria group (ACR 100-300 mg/g) or a macroalbuminuria group (ACR > 300 mg/g). Patients were followed up for 12 weeks, with 4 clinic visits, 4 weeks apart. At visit 2, spironolactone, 25 mg once daily, was initiated and continued for 4 weeks. At visit 3, spironolactone was discontinued. Clinical information was obtained at each visit as were serum chemistries and 24-hour urinary albumin excretion.ResultsTwenty-four patients with type 2 DM and albuminuria completed the study. Eleven patients had microalbuminuria and 13 had macroalbuminuria. Following treatment with spironolactone, urinary albumin excretion dropped from a mean ± SD of 404.6 ± 60.9 mg/d to 302.7 ± 52.7 mg/d (25.7% decrease, P < .001). In the microalbuminuria and macroalbuminuria groups, the urinary albumin excretion dropped 27.2% (P = .05) and 24.3% (P = .02), respectively. Despite a significant decrease in systolic blood pressure between visits 2 and 3 (141.2 ± 3.5 to 132.5 ± 3.6 mm Hg; P = .002), this change did not correlate to the change in albuminuria (r² = 0.02; P = .23). There were no withdrawals due to hyperkalemia.ConclusionSpironolactone is effective in further decreasing albuminuria in patients with type 2 DM who are already treated with ACE inhibitors. (Endocr Pract. 2008;14:985-992)     

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits

ObjectiveThe primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission.MethodsNoncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient.ResultsOf 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days.ConclusionThese results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.