Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally ...and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes.
We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access.
We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children.
Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas.
No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated ...with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and ...modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring and what the consequences of differential methylation are in subsequent generations are not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested the effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared with HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk.
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.
Frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) is a neurodegenerative disease primarily affecting the frontal and/or temporal cortices. However, a growing body of evidence ...suggests that the cerebellum contributes to biochemical, cognitive, and behavioral changes in FTLD-TDP. To evaluate cerebellar TDP-43 expression and function in FTLD-TDP, we analyzed TDP-43 protein levels and the splicing of a TDP-43 target, STMN2, in the cerebellum of 95 FTLD-TDP cases and 25 non-neurological disease controls. Soluble TDP-43 was decreased in the cerebellum of FTLD-TDP cases but a concomitant increase in insoluble TDP-43 was not seen. Truncated STMN2 transcripts, an indicator of TDP-43 dysfunction, were elevated in the cerebellum of FTLD-TDP cases and inversely associated with TDP-43 levels. Additionally, lower cerebellar TDP-43 associated with a younger age at disease onset. We provide evidence of TDP-43 loss of function in the cerebellum in FTLD-TDP, supporting further investigation into this understudied brain region.
Suicide rates in the United States have increased recently among Black men. To address this public health crisis, smartphone-based ecological momentary assessment (EMA) platforms are a promising way ...to collect dynamic, real-time data that can help improve suicide prevention efforts. Despite the promise of this methodology, little is known about its suitability in detecting experiences related to suicidal thoughts and behavior (STB) among Black men.
This study aims to clarify the acceptability and feasibility of using smartphone-based EMA through a pilot study that assesses the user experience among Black men.
We recruited Black men aged 18 years and older using the MyChart patient portal messaging (the patient-facing side of the Epic electronic medical record system) or outpatient provider referrals. Eligible participants self-identified as Black men with a previous history of STB and ownership of an Android or iOS smartphone. Eligible participants completed a 7-day smartphone-based EMA study. They received a prompt 4 times per day to complete a brief survey detailing their STB, as well as proximal risk factors, such as depression, social isolation, and feeling like a burden to others. At the conclusion of each day, participants also received a daily diary survey detailing their sleep quality and their daily experiences of everyday discrimination. Participants completed a semistructured exit interview of 60-90 minutes at the study's conclusion.
In total, 10 participants completed 166 EMA surveys and 39 daily diary entries. A total of 4 of the 10 participants completed 75% (21/28) or more of the EMA surveys, while 9 (90%) out of 10 completed 25% (7/28) or more. The average completion rate of all surveys was 58% (20.3/35), with a minimum of 17% (6/35) and maximum of 100% (35/35). A total of 4 (40%) out of 10 participants completed daily diary entries for the full pilot study. No safety-related incidents were reported. On average, participants took 2.08 minutes to complete EMA prompts and 2.72 minutes for daily diary surveys. Our qualitative results generally affirm the acceptability and feasibility of the study procedures, but the participants noted difficulties with the technology and the redundancy of the survey questions. Emerging themes also addressed issues such as reduced EMA survey compliance and diminished mood related to deficit-framed questions related to suicide.
Findings from this study will be used to clarify the suitability of EMA for Black men. Overall, our EMA pilot study demonstrated mixed feasibility and acceptability when delivered through smartphone-based apps to Black men. Specific recommendations are provided for managing safety within these study designs and for refinements in future intervention and implementation science research.
RR2-10.2196/31241.
Objective To compare the acceptability and efficacy of two methods of self administered bowel preparation for flexible sigmoidoscopy screening: a single phosphate enema and a single sachet of ...Picolax. Design Single blind, randomised trial. Setting Endoscopy units of two general hospitals. Participants 1442 men and women aged 55-64 years who had agreed to be screened by flexible sigmoidoscopy. Main outcome measures Attendance rates, compliance with allocated preparations, adverse effects, quality of bowel preparation, procedure time, and yield of neoplasia. Results Compliance with the enema was higher than with the Picolax (608 (84%) v 566 (79%); difference 6%, 95% confidence interval 2% to 10%). Almost half of those who refused Picolax used an enema at home. Wind, incontinence, and sleep distrubance were more frequent in the Picolax group than the enema group; bottom soreness was more frequent in the enema group. Around 30% (187) found the diet restriction required by Picolax difficult; 78% (471) found the enema easy to administer. The quality of preparation was better with the enema; the proportion of procedures complete to the descending colon was greater and the mean duration of the procedure was shorter. There was no significant difference in polyp detection rates. Conclusion A single phosphate enema self administered around one hour before leaving home is a more acceptable and effective method of preparing the distal bowel for flexible sigmoidoscopy than Picolax.
One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term ...treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response GH and insulin-like growth factor I (IGF-I) reduction. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.
To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly.
Double-blind, randomized trial.
Fourteen university-affiliated medical centers.
One hundred ...fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy.
Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months.
After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively.
Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.
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