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Contemporary Clinical Trials Mar 2024Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric...
BACKGROUND
Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate. However, guidance regarding when adjunct AOM should be started and how AOM should be used is unclear. Furthermore, an inherent limitation of current treatment guidelines is their "one-size-fits-all" approach, which does not account for the heterogeneous nature of obesity and high degree of patient variability in response to all interventions.
METHODS
This paper describes the study design and methods of a sequential multiple assignment randomized trial (SMART), "SMART Use of Medications for the Treatment of Adolescent Severe Obesity." The trial will examine 1) when to start AOM (specifically phentermine) in adolescents who are not responding to lifestyle therapy and 2) how to modify AOM when there is a sub-optimal response to the initial pharmacological intervention (specifically, for phentermine non-responders, is it better to add topiramate to phentermine or switch to topiramate monotherapy). Critically, participant characteristics that may differentially affect response to treatment will be assessed and evaluated as potential moderators of intervention efficacy.
CONCLUSION
Data from this study will be used to inform the development of an adaptive intervention for the treatment of adolescent severe obesity that includes empirically-derived decision rules regarding when and how to use AOM. Future research will test this adaptive intervention against standard "one-size-fits-all" treatments.
Topics: Adolescent; Child; Humans; Anti-Obesity Agents; Fructose; Obesity, Morbid; Pediatric Obesity; Phentermine; Topiramate; Weight Loss; Randomized Controlled Trials as Topic
PubMed: 38219798
DOI: 10.1016/j.cct.2024.107444 -
BMC Primary Care Mar 2024The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of...
BACKGROUND
The prevalence of obesity has been increasing worldwide and is associated with increased risk of morbidity and mortality. Weight management can reduce the risk of complications and improve the quality of life of patients with obesity. This study explored primary care physicians' (PCPs') attitudes and knowledge about weight management.
METHODS
An anonymous questionnaire was distributed to 400 PCPs between 2020 and 2021. The survey included questions on treatment approaches (pharmaceutical and surgical) and items regarding the respondents' demographic characteristics. We compared PCPs with low or high proactivity toward weight management. We explored attitudes and knowledge with the chi-square test for categorical variables or the Mann-Whitney test for continuous variables.
RESULTS
A total of 145 PCPs answered our survey (a response rate of 36.25%). More than half (53.8%) of the respondents showed low proactivity toward weight management in their practice. Proactive respondents were more likely to believe that pharmaceutical treatment effectively reduces weight and offered medical and surgical treatment options more frequently to their patients. Lack of knowledge was the most predominant reason for PCPs avoiding offering treatment to their patients, especially in less proactive PCPs (33.3% vs. 5.3%, p-value < 0.001). When comparing different pharmaceutical options, 46.6% of PCPs report they tend to prescribe liraglutide to their patients compared with only 11% who prescribe orlistat and 10.3% who prescribe phentermine (p-value < 0.001).
CONCLUSIONS
Many PCPs still do not actively provide obesity treatment despite improved awareness and therapeutic options. PCPs' proactivity and attitudes are vital to this effort.
Topics: Humans; Cross-Sectional Studies; Physicians, Primary Care; Israel; Quality of Life; Obesity; Pharmaceutical Preparations
PubMed: 38504167
DOI: 10.1186/s12875-024-02324-5 -
The Primary Care Companion For CNS... Feb 2024
Topics: Humans; Bipolar Disorder; Phentermine; Mania; Weight Loss
PubMed: 38395144
DOI: 10.4088/PCC.23cr03624 -
Saudi Journal of Gastroenterology :... May 2024Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe...
BACKGROUND
Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.
METHODS
Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy.
RESULTS
Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment.
CONCLUSION
In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.
PubMed: 38726916
DOI: 10.4103/sjg.sjg_428_23 -
Journal of Pharmaceutical and... Aug 2024As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially...
As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L NaHPO, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L NaHPO, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025-5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.
Topics: Tandem Mass Spectrometry; Anti-Obesity Agents; Liquid Phase Microextraction; Chromatography, High Pressure Liquid; Hair; Humans; Limit of Detection; Reproducibility of Results
PubMed: 38772203
DOI: 10.1016/j.jpba.2024.116236 -
Malaria Journal Jan 2024In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a...
Dynamics of malaria vector composition and Plasmodium falciparum infection in mainland Tanzania: 2017-2021 data from the national malaria vector entomological surveillance.
BACKGROUND
In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a periodical assessment of malaria vector composition and abundance, feeding and resting behaviours, and Plasmodium falciparum infection in different malaria epidemiological strata to guide the NMCP on the deployment of appropriate malaria vector interventions. This work details the dynamics of malaria vector composition and transmission in different malaria epidemiological strata.
METHODS
The MVES was conducted from 32 sentinel district councils across the country. Mosquitoes were collected by the trained community members and supervised by the NMCP and research institutions. Three consecutive night catches (indoor collection with CDC light trap and indoor/outdoor collection using bucket traps) were conducted monthly in three different households selected randomly from two to three wards within each district council. Collected mosquitoes were sorted and morphologically identified in the field. Thereafter, the samples were sent to the laboratory for molecular characterization using qPCR for species identification and detection of P. falciparum infections (sporozoites). ELISA technique was deployed for blood meal analysis from samples of blood-fed mosquitoes to determine the blood meal indices (BMI).
RESULTS
A total of 63,226 mosquitoes were collected in 32 district councils from January 2017 to December 2021. Out of which, 39,279 (62%), 20,983 (33%) and 2964 (5%) were morphologically identified as Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l., and as other Anopheles species, respectively. Out of 28,795 laboratory amplified mosquitoes, 13,645 (47%) were confirmed to be Anopheles arabiensis, 9904 (34%) as An. funestus sensu stricto (s.s.), and 5193 (19%) as An. gambiae s.s. The combined average entomological inoculation rates (EIR) were 0.46 (95% CI 0.028-0.928) for An. gambiae s.s., 0.836 (95% CI 0.138-1.559) for An. arabiensis, and 0.58 (95% CI 0.165-0.971) for An. funestus s.s. with variations across different malaria transmission strata. Anopheles funestus s.s. and An. arabiensis were predominant in the Lake and South-Eastern zones, respectively, mostly in high malaria transmission areas. Monthly mosquito densities displayed seasonal patterns, with two peaks following the rainy seasons, varying slightly across species and district councils.
CONCLUSION
Anopheles arabiensis remains the predominant vector species followed by An. funestus s.s. in the country. Therefore, strengthening integrated vector management including larval source management is recommended to address outdoor transmission by An. arabiensis to interrupt transmission particularly where EIR is greater than the required elimination threshold of less than one (< 1) to substantially reduce the prevalence of malaria infection.
Topics: Animals; Humans; Malaria; Anopheles; Plasmodium falciparum; Tanzania; Mosquito Vectors; Feeding Behavior; Malaria, Falciparum; Chlorphentermine
PubMed: 38243220
DOI: 10.1186/s12936-024-04849-7 -
Microbiological Research Mar 2024Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here,...
Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here, we have characterized a bacterial strain capable of degrading synthetic aminophosphonates. The strain was isolated from LC/MS standard solution. Genome sequencing indicated that the strain belongs to the genus Ochrobactrum. Whole-genome classification using pyANI software to compute a pairwise ANI and other metrics between Brucella assemblies and Ochrobactrum contigs revealed that the bacterial strain is designated as Ochrobactrum sp. BTU1. Degradation batch tests with Ochrobactrum sp. BTU1 and the selected aminophosphonates GS, EDTMP, aminomethylphosphonic acid (AMPA), iminodi(methylene-phosphonic) (IDMP) and ethylaminobis(methylenephosphonic) acid (EABMP) showed that the strain can use all phosphonates as sole phosphorus source during phosphorus starvation. The highest growth rate was achieved with AMPA, while EDTMP and GS were least supportive for growth. Proteome analysis revealed that GS degradation is promoted by C-P lyase via the sarcosine pathway, i.e., initial cleavage at the C-P bond. We also identified C-P lyase to be responsible for degradation of EDTMP, EABMP, IDMP and AMPA. However, the identification of the metabolite ethylenediaminetri(methylenephosphonic acid) via LC/MS analysis in the test medium during EDTMP degradation indicates a different initial cleavage step as compared to GS. For EDTMP, it is evident that the initial cleavage occurs at the C-N bond. The detection of different key enzymes at regulated levels, form the bacterial proteoms during EDTMP exposure, further supports this finding. This study illustrates that widely used and structurally more complex aminophosphonates can be degraded by Ochrobactrum sp. BTU1 via the well-known degradation pathways but with different initial cleavage strategy compared to GS.
Topics: Ochrobactrum; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Biodegradation, Environmental; Glyphosate; Organophosphonates; Phosphorus; Phentermine
PubMed: 38211497
DOI: 10.1016/j.micres.2024.127600 -
American Journal of Ophthalmology Case... Sep 2024This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly...
PURPOSE
This report describes the presentation of a 49-year-old woman with a branch retinal artery occlusion of the right eye in the setting of taking phentermine, a commonly used weight loss medication.
OBSERVATIONS
A 49-year-old woman presented with acute painless vision loss in her right eye and was found to have a branch retinal artery occlusion after taking prescribed dosages of phentermine for weight loss therapy. Fundus examination revealed retinal whitening in the distribution of the superior temporal branch retinal artery, and spectral domain optical coherence tomography demonstrated macular edema. Systemic evaluation was negative for cardiovascular, infectious, or autoimmune etiologies. Based on the retinal findings, the patient was diagnosed with phentermine associated branch retinal artery occlusion. She was followed for nine years with no further complications and her vision remained stable in the right eye.
CONCLUSIONS AND IMPORTANCE
This case highlights that phentermine, a commonly used weight loss medication, could be associated with ischemic retinopathies. Thus, clinicians should be aware that retinal vascular occlusions may not only occur in those who use recreational amphetamines but also in patients taking the prescribed dosages of a weight loss medication like phentermine.
PubMed: 38884112
DOI: 10.1016/j.ajoc.2024.102013 -
Obesity Research & Clinical Practice 2024
Topics: Humans; Phentermine; Topiramate; Duration of Therapy; Retrospective Studies; Australia; Obesity; Medical Records
PubMed: 38365507
DOI: 10.1016/j.orcp.2024.01.005 -
ACG Case Reports Journal Jun 2024Phentermine is an amine anorectic that acts as a sympathomimetic agent and undergoes hepatic metabolism predominantly through CYP3A4. It is commonly used as a mediation...
Phentermine is an amine anorectic that acts as a sympathomimetic agent and undergoes hepatic metabolism predominantly through CYP3A4. It is commonly used as a mediation to facilitate weight loss. Side effects of phentermine can include pulmonary hypertension, valvular heart disease, palpitations, increased heart rate or blood pressure, diarrhea, and cognitive impairment. Very rarely, phentermine usage has been associated with causing ischemic colitis. The mechanism of action for ischemic colitis from phentermine is not well defined but will be discussed in this review. We present a case of a woman who used phentermine daily for weight loss and was endoscopically confirmed to have ischemic colitis after presenting with abdominal pain and bloody diarrhea.
PubMed: 38841705
DOI: 10.14309/crj.0000000000001363