490 - Vitamin D and DM, Prostate CA Tx, How Shall We Connect?

From the Literature

1)  Vitamin D and Preventing Diabetes

Vitamin D testing, therapy, and supplementation have been studied to an astonishing extent over the last 20 years. All this study has resulted in few firm conclusions about its usefulness in preventing disease. Authors of a recent systematic review, however, present data that should at least make us think.

The authors looked in multiple databases for studies on patients with prediabetes who were asked to take vitamin D as a supplement (meaning without having been tested for deficiency). The looked for the diagnosis of diabetes after at least 2 years of supplementation as a primary outcome and for data about harms. There was no information about critical appraisal of the included studies and no assessment of heterogeneity.

Three studies were found: two evaluated doses of daily cholecalciferol (vitamin D3, 20K units/week and 4K units/day) and one evaluated eldecalcitol (a synthetic form of calcitriol, 0.75 mcg/day). Three studies were large, well-known studies and had similar inclusion criteria and baseline characteristics, which findings allay some of the concern about critical appraisal and heterogeneity assessment.

The mean vitamin D serum level in the groups was 25.4 ng/ml but only ~5% in each group fell below 30 ng/ml (the current threshold for insufficiency) suggesting some very low vitamin D levels in some subjects. The mean A1c in the groups was 5.9%. The pooled result from the studies shows a reduction in the rate of new diabetes in the vitamin D group vs. the placebo group (22.7% vs 25%, absolute risk reduction (ARR) 3.3% (from an adjusted calculation), number needed to treat (NNT) ~ 30). Obesity reduced the effect of cholecalciferol in preventing diabetes, but not for eldecalcitol. The vitamin D worked better for subjects whose baseline vitamin D level was less than 30, likely due to improvement in severe deficiency. There were no differences in other demographic categories and there were not differences in adverse events related to vitamin D (hypercalciuria, hypercalcemia, kidney stones, death).

An accompanying editorial expressed concern over the “unknown unknowns” of long-term vitamin D toxicity from dosages that are higher than the US recommended daily allowance of vitamin D (currently 400-800 IU/day) and right at the government-recommended tolerable upper intake level of 4000 IU.

John’s Comments:

This certainly deserves further study. The reduced effectiveness in the obese – the primary risk population with prediabetes – will limit the usefulness of these findings. Also, the potential toxicities of these higher doses should be thoroughly investigated before widespread adoption.

References:

·       Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes: A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. Published online February 7, 2023. Link

·       McKenna MJ, Flynn MAT. Preventing Type 2 Diabetes With Vitamin D: Therapy Versus Supplementation. Ann Intern Med. 2023;176(3):415-416. Link

From the Literature

2)  Prostate Cancer (PCa) Treatment – The More Things Change …

In the US in 2020, approximately 192,000 men received a diagnosis of prostate cancer and 33,000 died of the disease.  Despite recent advances in early detection (Take 3 #489) and treatment of localized cancer, management of the disease remains controversial.  The challenging aspects of risk stratification continue to drive both overtreatment and undertreatment.  Since the USPSTF updated its recommendations in 2012 and 2018, the incidence of localized disease has declined, whereas the incidences of regional and advanced cases have increased.  During this same period, cancer-specific mortality has remained unchanged.  The clinical outcomes from a recently published study may help to elucidate reasons for these findings.

Between 1999 and 2009 in the United Kingdom, 82,429 men aged 50 – 69 who received a prostate-specific antigen (PSA) test were enrolled in the Prostate Testing for Cancer and Treatment (ProtecT) trial.   Localized prostate cancer was diagnosed in 2664 men.  Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.

At a median follow-up of 15 years (range, 11 to 21), the results were compared with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).  Follow-up was complete for 1610 patients (98%).  With regard to the primary outcome, death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). 

In looking at secondary outcomes, death from any cause occurred in 356 men (21.7%), with similar percentages in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group.  Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively.

Across the 3 treatment groups, no differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score and prostate cancer–specific survival was approximately 97% regardless of the trial-group assignment.  Radical treatments (prostatectomy or radiotherapy) reduced the incidence of metastasis, local progression, and long-term androgen-deprivation therapy by half as compared with active monitoring.

The authors concluded that after 15 years of follow-up, the choice of therapy for men newly diagnosed with localized prostate cancer involves weighing short-term and long-term trade-offs between benefits and harms associated with treatments, including urinary, bowel, and sexual function, as well as the risks of progression of disease. 

Mark’s Comments:

Getting 15-year data for a reasonably sized study with such good follow-up would in general be good news.  In the case of this study, there seems good news and bad news.  The good news is that for low-grade prostate cancer, there appears to be many viable treatment options and that regardless of the approach, 15-year prostate-specific mortality data is quite low.  The “bad news” is that with all these potential options, how to proceed for any particular patient can be quite confusing.  Add to this dynamic the fact that over the period of this study, both diagnostic and treatment options have continued to advance and improve, and those treatment options don’t have the same long-term data for effectiveness, and we’re left with a lot of uncertainty, yet again.  Well, at least it’s “better informed uncertainty ….”   

References:

·       Hamdy F, et al.  Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.  N Engl J Med.  March 11, 2023.  Link

·       Sartor O.  Editorial:  Localized Prostate Cancer – Then and Now.  N Engl J Med.  March 11, 2023.  Link

From PeerRxMed ( www.PeerRxMed.org )

3)  How Then Shall We Connect? 

“Nothing new that is really interesting comes without collaboration.”  James D. Watson (discoverer of the double-helix structure of DNA with Francis Crick)

In the February 27^th blog, "How Do We Gather Together When We No Longer Do?", I expressed concern regarding the worsening impersonal nature of healthcare delivery and the disconnection between both intraspecialty and interspecialty colleagues, all with negative consequences for patient care.   As this dynamic has been exacerbated by both the advent of the electronic health record and the COVID pandemic, I raised this question to tap into the collective wisdom of our PeerRxMed community:  “At a time when regular physical (or virtual) gathering may not be practical or even desired, how might we gain more familiarity and connection with those whom we regularly share in patient care?” and promised to follow-up with some highlights from those responses in a future blog.

The responses from colleagues in our PeerRxMed collective were heartening and revealed a common theme:  More meaningful professional connection will not happen without both explicit intention and initiative taking.  Here are a few examples (which I have edited):

“I especially feel this disconnection being a PCP affiliated with a large health system.  I don't actually know to whom I am referring my patients most of the time!   What I have done to better connect is to briefly respond to the notes that consultants send in the EHR, often with a simple, ‘Thank you, this was very helpful.’  To my surprise, I often get a response back with more detail or nuance.  The direct notes help us remember one another as well.” 

“As a subspecialist, referrals are my lifeblood and communication with my referring colleagues essential.  One thing I have done for many years is to reach out (preferably via video or phone) and personally welcome each new primary care clinician who comes into the community.   I also give them my personal cell number so they can call or text with questions.  The care is better, and, not surprisingly, business is booming.”

“I work as part of a larger health system which has experienced much turnover.  I “started small” by getting to know one or two colleagues in each department where I regularly refer and would send them questions preferentially.   During COVID we would meet for 5-10 minutes via video just as an introduction.   Over time I have expanded that network as needed.  It helps to not even try to remember all the colleagues in any department or section and the connections I do have help me navigate in their department when they feel a colleague would be better suited for a particular question.”

“The hospital system where I was employed set up an event where the PCP’s could meet many of the specialists in a sort of “speed dating” set up.  PCPs sat on one side of the table across from a specialist on the other side, moving down every few minutes to meet or re-acquaint themselves with another specialist.  This was received very well and was actually a lot of fun.”

As you can see, it would seem that connection only happens through … connecting!  Which led to an insightful question from one of our colleagues:  “How do you get introverts or those who are less comfortable socially to connect?”   His suggestions included carved out time on committees, community service activities, and empowering “super connectors” to bring a couple of providers together for lunch or coffee around a particular topic.   

What becomes obvious in all the responses is that, despite a narrative promoted by some administrative leaders that clinicians are “interchangeable parts,” those who do this work recognize the essential nature of personal relationships to promote optimal patient care.  And doing so makes our work much more enjoyable and meaningful.   I’m in ….

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org