Sara Karlovitch

A recent literature review and meta-analysis of patients treated with hydroxyurea, a standard treatment for 

 (PV), found a stable rate of thrombosis over time, although residual rates for these patients were higher than for the general population.

PV is a myeloproliferative neoplasm (MPN) characterized by high frequency of thrombosis and a tendency to transform into acute myelogenous leukemia (AML) or myelofibrosis (MF). Patients must be assessed for the potential risk of developing major thrombotic or hemorrhagic complications. High-risk patients are those over the age of 60 or with prior thrombotic complications.

After initially selecting 429 reports, the authors chose 16 studies of adults over 18 were chosen for review. The studies were published between 2008 to 2018. All the studies had at least 20 participants and were prospective and retrospective cohort studies. Case reports and narrative reviews were not included. In total, 3236 patients were analyzed. The review, published in 

, used a random effect logistic model. Incidences, study heterogeneity, and confounder effects were estimated for each outcome at different follow ups.

Mortality and myelofibrosis varied depending on follow-up duration, but incidences of thrombosis and acute myeloid leukemia (AML) were stable over time. Overall incidence of thrombosis was about 3% per year, determined by pooling event rates from each study.

Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively, based on 2552 patients and 469 events. Mortality for the same intervals under the same conditions was 2.4%, 12.6%, and 56.2%.

Previous cardiovascular complication predicted higher incidence of bleeding, and cumulative AML incidence over 10 years was about 4%.

Incidence of transformation to MF and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5% at 5 years and 33.7% at 10 years; overall mortality was 12.6% and 56.2% at 5 and 10 years, respectively. The researchers noted that the estimates rise or fall with age at the start of follow up, with the odds of MF increasing on average 6% for each year of age, while those of death rise by 21%.

The researchers said their findings can help design comparative clinical trials with new critical end points for efficacy.

Ferrari A, Carobio A, Masciulli A, et al. Clinical outcomes under hydroxyurea treatment in polycythemia vera: A systematic review and meta-analysis. 

104(12): 2391-2399. doi:10.3324/haematol.2019.221234.

Articles

Mortality and myelofibrosis varied depending on follow-up duration in this review of patients with polycythemia vera treated with hydroxyurea, and incidences of thrombosis and acute myeloid leukemia (AML) were stable over time.

Rates of Thrombosis in Patients Treated With Hydroxyurea Fairly Stable Over Time, Review Finds

Craniosacral therapy (CST) may have major therapeutic benefits to those suffering from chronic pain, a new literature 

 found. The literature review examined randomized controlled trials for craniosacral therapy (CST) in patients with migraine and other conditions that cause pain.

Chronic pain, which is the leading global cause of disability, is increasing in prevalence. Migraine, headaches, and low back and neck pain all fall into the chronic pain category and, according to researchers, all age groups can be affected.

The literature review found no serious adverse events reported in 10 studies used in the meta-analysis. Compared with sham treatments, CST had a greater effect on pain intensity and disability at the 6-month mark. Secondary outcomes also improved in patients who underwent CST as opposed to sham treatments. Patients’ mental quality of life after 6 months was the only exception to this finding.

Specifically, CST showed better postintervention effects on:

Pain intensity: Standardized mean differences (SMD), —0.32; 95% CI, −&thinsp;0.61 to –0.02 and disability: SMD, &thinsp;–0.58; 95% CI&thinsp;−&thinsp;0.92 to –0.24, compared to usual treatment

Pain intensity: SMD&thinsp;, —0.63; 95% CI&thinsp;, −0.90 to –0.370, and disability: SMD, &thinsp;–0.54; 95% CI&thinsp;, −0.81 to –0.28, compared to manual/non-manual sham

Pain intensity: SMD, &thinsp;—0.53; 95% CI&thinsp;, −&thinsp;0.89 to –0.16, and disability: SMD&thinsp;,&thinsp;–0.58; 95% CI&thinsp;,−&thinsp;0.95 to –0.21, compared to active manual treatments.

The final analysis included 681 patients with chronic pain.

“In comparison to manual and non-manual sham controls, CST resulted in significantly greater pooled effects of a medium to large size directly after the end of the intervention as well as 6 months after randomization for pain intensity, functional disability, physical quality of life, and global improvement,” the authors stated. They continued, “Effects tended to be higher in comparisons of studies with blinded patients as well as patients with neck pain or lateral epicondylitis compared to those with fibromyalgia or migraine.”

The study’s limitations included a small number of studies in the meta-analysis, unclear risks of biases, and lack of subgroup analyses. According to authors, more research is needed to corroborate the effects and safety of CST as a viable tool to treat chronic pain.

Haller H, Lauche R, Sundberg T, Dobos G, Cramer H. Craniosacral therapy for chronic pain: a systematic revie and meta-analysis of tandomized controlled trials. 

 2019; 21(1). doi:10.1186/s12891-019-3017-y.

The literature review examined randomized controlled trials for craniosacral therapy (CST) in patients with migraine and other conditions that cause pain.

 Chronic Pain in Migraine May Be Mitigated by Craniosacral Therapy

Individuals’ susceptibility to genetic and epigenetic factors may be responsible for the transformation of episodic 

 to chronic migraine in some patients, according to a new 

Migraine is a life span disorder and affects about 15% of the general population. According to the World Health Organization, migraine is the most prevalent, disabling, and long-term neurological condition when accounting for years lost due to disability. The review aimed to discuss what possible mechanisms are behind a largely unknown evolutive process.

Genetic factors may determine how susceptible a person is to a migraine attack while environmental factors may trigger an attack, according to the review. Genome-wide association studies, which test for differences in allele frequencies of single nucleotide polymorphisms over the genome in migraine patients and controls, found that multigenetic variants, as opposed to a single gene, can contribute to migraine susceptibility.   

Epigenetics, or “modification of gene expression without altering the underlying DNA sequence” may also play a factor. However, epigenetics is a new area of research and only a handful of studies have been conducted on patients with migraine. Some studies found cortical structural changes in patients but results are unclear as to whether cortical thinning or thickening took place in the brain. Structural changes like gray matter changes may also be a cause.

Many factors can trigger a migraine attack, and stess and lack of sleep “are probably the most common triggers,” according to the review. The researchers divide migraines into a preliminary phase, a pain phase, and a postdrome phase, as migraine attacks tend to follow patterns. An aura phase will occur in around 15-20% of patients. During the postdrome phase, about 80% of patients report one non-headache symptom.

 “To date, studies failed to shed any light on how such genetic alterations may be responsible for migraine pathophysiology or any evolutive mechanism” the review states. “On the other hand, anatomical changes in the brain of a migraine patient exist even from early childhood, but they do not seem to have any functional consequences.”

Migraine is an evolutive condition, even in its episodic form. According to authors, different mechanisms such as cortical excitability in the aura phase and hypothalamic alterations in the premonitory phase are involved in the evolutive process of the attack.

“The causality dilemma of whether such changes are responsible for how migraine evolves, or whether migraine mechanisms drive these anatomic changes, remains to be answered” the review states.

Andreou AP, Edvinsson L. Mechanisms of migraine as a chronic evolutive condition [published online December 23, 2019].

Individuals’ susceptibility to genetic and epigenetic factors may be responsible for the transformation of episodic migraine to chronic migraine in some patients, according to a new review published in The Journal of Headache and Pain.

Evidence Shows Genetic, Epigenetic Factors May Be Responsible for Migraine Transformation

Patients with cancer who also have viral infections, such as 

, hepatitis B virus (HBV), and hepatitis C virus (HCV) should not be excluded from immune checkpoint inhibitor (ICI) studies, according to a new study published in the 

Although the researchers state that more studies are needed to validate their findings, they found that patients who also had HIV, HBV, or HCV who were being treated with ICI therapy had similar rates of efficacy and toxicity to patients without chronic viral infections. Additionally, found no viral reactivation. Tumor responses occurred in patients with HIV with low CD4 T-cell counts.

 looked at patients with advanced-stage cancers and HIV, HBV, or HCV infection treated with ICI therapy at 5 MedStar Health hospitals from January 2011 to April 2018.

Previously, patients with chronic viral infections were excluded from ICI therapy, a type of cancer immunotherapy that works through suppression of immune inhibitory pathways such as the programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis and the cytotoxic lymphocytes antigen proteins (CTLA-4) pathway. 

From the MedStar database, researchers identified 50 patients who fit the study criteria. Of that group, 16 were living with HIV, 29 with HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. The median age was 62 years, and most of the patients were treated with  anti-PD-(L)1 monotherapy while 1 was treated with a combination of ipilimumab and nivolumab;  another 6

patients were treated with anti-PD-(L)1/chemotherapy/targeted therapy combination. The most common type of cancer in the HIV cohort was non-small cell lung cancer. In the HBV/HCV cohort, hepatocellular carcinoma was the most common cancer.

In the HIV cohort (n&thinsp;=&thinsp;21), any grade immune-related adverse events (irAEs) were 24% with grade&thinsp;≥&thinsp;3 irAEs 14%.

Among 5 patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cell counts were observed.

Among RECIST evaluable patients, (n&thinsp;=&thinsp;18) the overall response rate (ORR) was 28% with 2 complete responses (CR) and 3 partial responses (PR). Responders included 2 patients with low baseline CD4+ T-cell counts.

In the HBV/HCV cohort (n&thinsp;=&thinsp;34), any grade irAEs were 44% with grade&thinsp;≥&thinsp;3 irAEs  in 29%. RECIST confirmed ORR was 21% (6 PR). Among the 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), there was no evidence of viral reactivation.

The study had 2 limitations-viral parameters were not collected and tumor assessment was not performed consistently.

However, the authors concluded that “toxicity and efficacy rates were similar to those observed in patients without chronic viral infections, supporting the use of ICI therapy in this patient population and the inclusion of such patients’ in future ICI-based trials.”

Additional studies are needed, they said.

Shah NJ, Al-Shbook G, Blackburn M, et al. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection. 

 2019;7(1):353. doi: 10.1186/s40425-019-0771-1.

Although the researchers state that more studies are needed to validate their findings, they found that patients who also had HIV, HBV, or HCV who were being treated with ICI therapy had similar rates of efficacy and toxicity to patients without chronic viral infections.

Sara Karlovitch

Articles

Rates of Thrombosis in Patients Treated With Hydroxyurea Fairly Stable Over Time, Review Finds

Chronic Pain in Migraine May Be Mitigated by Craniosacral Therapy

Evidence Shows Genetic, Epigenetic Factors May Be Responsible for Migraine Transformation

Cancer Immunotherapy Likely Safe, Effective for Those With HIV, Other Infections, Study Suggests