retrospective studies

Question: Are higher doses of buprenorphine treatment for opioid use disorder associated with improved retention in treatment when use of fentanyl (vs heroin) is more prevalent?

Findings: In this cohort study of 6499 patients initiating buprenorphine treatment between 2016 and 2020, those prescribed the recommended daily dose (16 mg) were at significantly greater risk of treatment discontinuation within 180 days than those prescribed a higher dose (24 mg).

Meaning: The results of this study suggest that the value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

Normal pressure hydrocephalus is a form of adult hydrocephalus with ventriculomegaly in the absence of any structural blockage of the cerebrospinal fluid circulation.

Normal pressure hydrocephalus is a partially reversible cause of dementia, manifesting with a triad of cognitive impairment, gait disturbance and urinary incontinence.

A detailed cognitive assessment, neurologic examination and brain imaging is necessary to exclude alternative causes and confirm the diagnosis.

High-volume lumbar puncture with pre- and postprocedure gait assessment is recommended as a confirmatory test before a decision is made regarding therapeutic interventions such as shunting.

Background
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings
We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Author summary
Why was this study done?
Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.
We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.
We do not know about the extent to which different features of long-COVID co-occur.
What did the researchers do and find?
This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.
What do these findings mean?
Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.
The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.
The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.

Background: Vitamin D is essential for bone health and probably the health of most nonskeletal tissues. Vitamin D deficiency is widespread, and recommended doses are usually inadequate to maintain healthy levels. We conducted a retrospective observational study to determine whether the recommended doses of vitamin D are adequate to correct deficiency and maintain normal levels in a population seeking health care. We also sought to develop a predictive equation for replacement doses of vitamin D.

Methods: We reviewed the response to vitamin D supplementation in 1327 patients and 3885 episodes of vitamin D replacement and attempted to discern factors affecting the response to vitamin D replacement by conducting multiple regression analyses.

Results: For the whole population, average daily dose resulting in any increase in serum 25-hydroxyvitamin D level was 4707 IU/day; corresponding values for ambulatory and nursing home patients were 4229 and 6103 IU/day, respectively. Significant factors affecting the change in serum concentrations of 25-hydroxyvitamin D, in addition to the dose administered, are (1) starting serum concentration of 25-hydroxyvitamin D, (2) body mass index (BMI), (3) age, and (f) serum albumin concentration. The following equation predicts the dose of vitamin D needed (in international units per day) to affect a given change in serum concentrations of 25-hydroxyvitamin D: Dose = [(8.52 - Desired change in serum 25-hydroxyvitamin D level) + (0.074 × Age) - (0.20 × BMI) + (1.74 × Albumin concentration) - (0.62 × Starting serum 25-hydroxyvitamin D concentration)]/(-0.002). Analysis of the dose responses among 3 racial groups-white, black, and others-did not reveal clinically meaningful differences between the races. The main limitation of the study is its retrospective observational nature; however, that is also its strength in that we assessed the circumstances seen in usual health care setting.

Conclusions: The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. About 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients.