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Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity

Author/s: 
Ghusn, W., De la Rosa, A., Sacoto, D.

Importance No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).

Objective To study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity.

Design, Setting, and Participants This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded.

Exposures Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months.

Main Outcomes and Measures The primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months.

Results The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005).

Conclusions and Relevance The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.

Keywords 
Cohort Studies overweight Retrospective Studies middle aged weight loss

Syncope and the Risk of Subsequent Motor Vehicle Crash A Population-Based Retrospective Cohort Study

Author/s: 
Staples, J. A., Erdelyi, S., Merchant, K., Yip, C., Khan, M., Redelmeier, D. A., Chan, H., Brubacher, J. R.

Importance Medical driving restrictions are burdensome, yet syncope recurrence while driving can cause a motor vehicle crash (MVC). Few empirical data inform current driving restrictions after syncope.

Objective To examine MVC risk among patients visiting the emergency department (ED) after first-episode syncope.

Design, Setting, and Participants A population-based, retrospective observational cohort study of MVC risk after first-episode syncope was performed in British Columbia, Canada. Patients visiting any of 6 urban EDs for syncope and collapse were age- and sex-matched to 4 control patients visiting the same ED in the same month for a condition other than syncope. Patients’ ED medical records were linked to administrative health records, driving history, and detailed crash reports. Crash-free survival among individuals with syncope was then compared with that among matched control patients. Data analyses were performed from May 2020 to March 2022.

Exposures Initial ED visit for syncope.

Main Outcomes and Measures Involvement as a driver in an MVC in the year following the index ED visit. Crashes were identified using insurance claim data and police crash reports.

Results The study cohort included 43 589 patients (9223 patients with syncope and 34 366 controls; median [IQR] age, 54 [35-72] years; 22 360 [51.3%] women; 5033 [11.5%] rural residents). At baseline, crude MVC incidence rates among both the syncope and control groups were higher than among the general population (12.2, 13.2, and 8.2 crashes per 100 driver-years, respectively). In the year following index ED visit, 846 first crashes occurred in the syncope group and 3457 first crashes occurred in the control group, indicating no significant difference in subsequent MVC risk (9.2% vs 10.1%; adjusted hazard ratio [aHR], 0.93; 95% CI, 0.87-1.01; P = .07). Subsequent crash risk among patients with syncope was not significantly increased in the first 30 days after index ED visit (aHR, 1.07; 95% CI, 0.84-1.36; P = .56) or among subgroups at higher risk of adverse events after syncope (eg, age >65 years; cardiogenic syncope; Canadian Syncope Risk Score ≥1).

Conclusions and Relevance The findings of this population-based retrospective cohort study suggest that patients visiting the ED with first-episode syncope exhibit a subsequent crash risk no different than the average ED patient. More stringent driving restrictions after syncope may not be warranted.

Keywords 
middle aged Retrospective Studies middle aged motor vehicle accidents Medical driving restrictions

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Author/s: 
Coupland, C.A.C., Hill, T., Dening, T., Morriss, R., Moore M., Hippisley-Cox J.

IMPORTANCE:

Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.

OBJECTIVE:

To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.

DESIGN, SETTING, AND PARTICIPANTS:

This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.

EXPOSURES:

The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).

MAIN OUTCOMES AND MEASURES:

Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.

RESULTS:

Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementiarisk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.

CONCLUSIONS AND RELEVANCE:

Exposure to several types of strong anticholinergic drugs is associated with an increased risk ofdementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

Keywords 
dementia middle aged cognition Antipsychotic drugs
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