Neurodegenerative Disease: An Interdisciplinary Approach

Introduction

Neurodegenerative disease (ND) is a broad medical term used to describe a range of conditions that primarily affect the neurons in the human brain. For example, Alzheimer’s disease, Parkinson’s disease, prion diseases, motor neuron disease, Huntington’s disease, spinocerebellar ataxia, spinal muscular atrophy, and more. The population of the United States is aging, and an ever-increasing number of Americans are afflicted with NDs. Unfortunately, the pathophysiological mechanisms of many of these diseases remain unknown. What is primarily known is neurons, termed building blocks of the nervous system, are electrically excitable cells that transmit and integrate information, acting as affecter cells of nerve cells, muscle, or gland cells. When neurons become damaged or die, they cannot be replaced or reproduce to compensate for the loss. Therefore, the degeneration of these crucial cells often causes problems with movement, or mental functioning, leading to an often slow and painful death. These diseases affect many areas of a patient’s life and their loved ones. For instance, Amyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. One discipline involved in the natural sciences, the biology of the disease affects the upper motor neurons, these direct lower motor neurons to produce movements such as walking or chewing. Subsequently, lower motor neurons control movement in the arms, legs, chest, face, throat, and tongue. Another discipline under natural sciences is psychology, the effect the disease has on the mind and behavior of a patient. For example, ND patients might have higher comorbidity of depression compared to others in their age bracket. Finally, focusing on the humanities, the patient families are affected by sociology factors. Often, the patient feels like a burden to the primary caregiver, and the caregiver can undergo extreme amounts of stress. In summary, to accurately assess the effects of NDs on a patient’s life, an interdisciplinary approach is imperative.

Biology

The lack of knowledge of the pathophysiological mechanisms of neurodegenerative diseases impacts the efficacy of a timely diagnosis, accurate prognosis, and effective treatment. Specifically, the average diagnostic delay, or time from onset of symptoms to diagnosis of ALS, is about a year. The diagnosis is based mostly on clinical and electrodiagnostic evaluation, such as an electromyography (EMG) (to determine the electrical activity of muscle fibers), which can be challenging in the early stages of the disease. Four domains have been identified to predict subsequent cognitive impairment and ND; data patterns of memory and performance, cardiovascular factors, genetic markers, and brain activity (Nilsson, 2006). A gradual impairment in the performance of memory testing might be an indicator of preclinical dementia. But, to analyze the decline, there must first be an assessment of typical memory decline, since a deterioration is also a common finding in healthy aging. Further, studies show that brain abnormalities, mainly white matter lesions, have an association with blood pressure and negatively impact brain function. Also, many genetic markers that correlate with neurodegeneration are involved with protein folding. For instance, misfolding of prions, and other proteins might aggregate in and around neurons, to form structures like amyloid plaques. Additionally, it is essential to consider how biologically determined factors that induce various experience-based factors could counter structural brain changes. The complexity of this model demonstrated that one single marker should not be used as a significant predictor. Future research should identify individuals who have multiple of the previously listed biomarkers. However, many challenges or limitations arise when performing this research. For example, many of the studies must be longitudinal, but often experience a significant decrease in sample size when more limits or specifications are added to a cohort. Therefore, while studies exist on the clinical diagnosis and predicting factors of ND, there are many obstacles to achieve substantial findings.

Recent research investigates the importance of personal medical history when evaluating a patient’s risk for ND. A study performed by LoBue and others sought to identify a possible relationship between traumatic brain injury (TBI) history and the advancement of mild cognitive impairment (MCI) to Alzheimer’s Disease (AD), the most common ND (2018). One would hypothesize that following multiple episode of TBIs experienced, an individual might experience a more rapid or accelerated progression from MCI, a transitional stage, to AD by increasing the pathological burden. This study involved 2,719 subjects with MCI obtained from the National Alzheimer’s Coordinating Center (NACC), an extensive database of standardized clinical and neuropathological research data. Traumatic brain injury was defined, including a loss of consciousness without chronic deficit occurring greater than one year before the diagnosis of MCI. Subsequently, survival analyses determined if the history of TBI predicted progression from MCI to AD, and random regression models were used to see if the history predicted the rate of decline. The researchers concluded that TBI history was not significantly associated with progression to a diagnosis of Alzheimer’s disease, and TBI history was a nonsignificant predictor for the rate of decline. However, mild cognitive impairment was diagnosed with a mean of about three years earlier in patients with TBI history. Therefore, the incidence of a traumatic brain injury might reduce the threshold for the onset of MCI and certain neurodegenerative conditions. The previously described studies that focus on the biology of NDs showcase the complexities of determining the pathophysiological mechanisms, diagnosing the diseases, identifying significant predictors, and compiling a final cohort to study.

Psychology

The progression of a disease such as Alzheimer’s disease, results in an individual’s impairment of cognitive functions, including memory and comprehension. This effect is often debilitating and can lead to a patient being institutionalized in long-term care (LTC) facility, such as a nursing home. Thus, a patient is experiencing behavioral and psychological symptoms of dementia (BPSD) that are affected by internal and external changes. Interestingly, a study set out to determine the effectiveness of built environment interventions in managing BPSD among the residents in LTCs (Soril et al., 2014). To accomplish this, Soril et al. conducted a systematic review of the literature published from 1995 to 2013. The built environment is commonly described as the constructed physical surroundings where a patient performs activities of daily living (ADL). A specific example of a built environment intervention could include the addition of a new object, construction of an outdoor area, or relocation to an entirely novel living environment. The results of the systematic review concluded that of the three categories of intervention; change of existing physical space, the addition of physical objects, and type of living environment, only one cohort of patients reported improvements in BPSD. The patients that demonstrated improvements in BPSD was a redesign of physical spaces. Conversely, the individual addition of physical objects showed no difference, and the novel living environment sample exhibited a decreased or no difference in BPSD. Therefore, there is inconclusive evidence to suggest which built environment intervention is clinically superior in long-term care settings. Further studies are required to demonstrate the feasibility and effectiveness of responses about the patient’s physical surroundings.

While there is not much evidence for the support of physical surroundings in improving a patient with NDs’ experience, there may be evidence for the help of loved ones. For instance, a neurodegenerative disease affects not only the ill individual but also their partner, parents, children, and friends. Correctly, one study verified the effectiveness of the couple’s treatment in models of rehabilitation wherein the partner often becomes the primary caregiver (Ghedin et al., 2017). The goal of treatment is to decrease the stress on both parties during this time of shifting roles, particularly in emotional and sexual intimacy, and to allow the ailing one to attain some degree of autonomy. Several studies have shown that the caregivers’ quality of life is miserable and inversely proportional to the burden of the caregiver. Fourteen patients affected by NDs and their spouses participated in emotionally focused couple therapy (EFT). EFT is an evidence-based approach for helping partners to their emotions of fear, sadness, and loneliness. Further, the therapists work in three phases; cycle de-escalation, restructuring interactional positions, and integration. Ultimately, the goal of EFT is to create and strengthen secure attachment bonds between couples so they can share their feelings and face uncertainty and life-threatening situations in the context of illness. The researchers measured the quality of life and relationship satisfaction for both partners before treatment and after treatment. The results show an improvement in the quality of life, couple adaptation, and couple contentment. Through the expression of the underlying feelings of fear, guilt, shame, and sadness, it is possible to give each spouse a partner that offers support, therein, easing the caregiver burden and patient’s guilt. Further studies should increase the sample size, which subsequently decreases the margin of error, producing significant findings.

Sociology

Sociology helps to explain the impact that fatal, progressive diseases have on family relations. The nature of cognitive deterioration exerts a unique stressor, which significantly affects an individual’s relationships. In addition to the patient coping or possibly attempting to cover the memory loss, the illness also exerts a disruptive influence on families. A study conducted in 1993 examined the decisions to place a person in LTC as a function of caregiver stress (Aneshensel, Pearlin, & Schuler). In this research, three annual interviews were performed with a sample size of 555 caregivers, who are a parent or spouse of a patient with AD. All of the patients were cared for at home, but 192 were later placed in institutional care, and 146 passed away. The results showed an evident competition of conflicting interests of family members. Such as the cessation, or end of in-home care significantly reduces role-related stress. However, patients who are hospitalized in an LTC facility are more likely to die than those who remain at home. There may be many possible reasons for this shift in mortality when institutionalized; for instance, the individual may feel isolated from their loved ones, or the change in routine hurts their disease. The interests of the caregiver and patient are not equally met with in-home care or an LTC placement. One might infer that this quandary adds a higher amount of stress, burden, and anguish of having a loved one with an ND. Further studies should include more research into social pressure with a focus on the well-being of the person exposed to stress and consequential health-relevant outcomes. This improvement could apply to the chronically ill person suffering from ND and the health outcomes of the caregiver. A longitudinal study might reveal that due to the chronic stress, the once health caregiver develops a disorder.

As previously established, the cost of community obligation and care for the fatally ill increases the caregiving burden on families with members who have NDs. Also, societal norms and expectations differ depending on ethnicity. Ethnicity is just one factor that influences caregiving duties. For instance, a considerable amount of previous research that focuses on Black families presents an interesting dichotomy; an unstable, disorganized nature of Black nuclear families indicated by the percentage of single-parent families or Black families with extensive ties to extended family and a broader sense of familial responsibility compared to White families. These differences might stem from economic disadvantage among Blacks or differences in Black and White norms of family obligation. A particular study used data from interviews with 78 parents and 70 siblings of patients with mental illness scheduled for release from a mental hospital (Horwitz & Reinhard, 1995). One hypothesis could be there are no ethnic differences in caregiving duties between Black and White parents. Secondly, Black parents will report less burden from their caregiving duties than White parents. This hypothesis would imply that although both ethnicity’s parents might provide comparable levels of caregiving-their responsibilities might be more normative for Black, thus, more arduous for Whites. Thirdly, Black siblings will report more extensive caregiving duties than White siblings. Lastly, Black siblings will feel less burdened by their caregiving duties than White siblings. Due to the expectation that Blacks have a greater sense of familial obligation, sibling caregiving might be more normative. The results of this study only add to the contradictory nature of findings regarding Black families and extended families. The findings indicate that Black and White parents have equal caregiving duties, although White parents report significantly more caregiver burden. Similarly, Black siblings identify more caregiving responsibilities than White siblings but also report less burden. There are many limitations to this study; for example, the sample size of Black parents and siblings is minimal. Contrastingly, the study controlled for income, gender, age, diagnosis, perceived stigma, and residence when considering these ethnic differences. In summary, the results indicate that ethnicity can be a vital factor affecting levels of caretaking for those with serious mental illness, such as NDs.

Conclusion

While this analysis of neurodegenerative disease paints a bleak picture for individuals diagnosed with these terrible afflictions and their families, there may be strategies to delay the onset of symptoms or prevent NDs. Smith analyzed healthy cognitive aging and behavioral prevention strategies that could help maintain high levels of cognition (2016). These strategies could also reduce the burden-medical, social, and economic, associated with aging and diseases that often accompany it. Specifically, brain health and cognitive resilience begin in utero. Also, there are antipoverty, perinatal health, preschool education, physical education, and education enrichment programs that are all a part of a national dementia prevention strategy. However, more considerable resources must be directed to behavior research. One avenue to pursue this could be the National Institutes of Health (NIH), expanding its research on cognitive disorders of aging, which could be approached from a biology, psychology, and sociology perspective. This research would provide a comprehensive and informed view of the patient and patient-family care. While there is no perfect treatment of these ruthless diseases, an ideal treatment would be developed on a case-by-case basis using an interdisciplinary approach. Every individuals’ needs are different, and this is imperative to remember when treating someone who appears to be slowly losing their individuality. Firstly, there should be increased resources for patients and families. This could be in the form of patient education, i.e., keeping the patient informed throughout the process to reduce their stress as much as possible. Besides, access to therapy is imperative to lessen the burden on the patient and improve their relationship with their loved ones; therapy could also be beneficial to ease the burden of guilt that comes with the cessation of caregiving. Finally, continued communication between patients and their families after institutionalization and communication between LTC facilities and families could both be beneficial for the health of all parties involved. Secondly, education is the easiest way to empower somebody to make informed decisions and restore a semblance of autonomy or power a patient once had. This education could include early signs if NDs, prevention, predictive markers, or even simple ways to sharpen cognitive function daily. While previous research exists across many subdisciplines of ND, there are many established limitations. Further research could be done to investigate the economic strain family experiences when a loved one is diagnosed with these diseases. Also, there are many laws and public policies that show a total disregard for human-centered health care but are solely focused on financial gain. Another possible topic is the ethical obligation a caregiver faces when deciding to institutionalize a loved one. At what point is harm being done to both parties, or when is it better for a caregiver in the long run to cease care. Above all, it is imperative that those with positions of power, such as physicians studying the pathophysiological mechanisms, psychologists focused on built environments, and sociologists studying ethnicity and NDs, all remember to involve humanness in healthcare.

References

• Aneshensel, C. S., Pearlin, L. I., & Schuler, R. H. (1993). Stress, Role Captivity, and the Cessation of Caregiving.
  
  Journal of Health and Social Behavior
  
  ,
  
  34
  
  (1), 54.
  
  https://doi.org/10.2307/2137304
  
• Ghedin, S., Semi, A., Caccamo, F., Caldironi, L., Marogna, C., Piccione, F., … Vidotto, G. (2017). Emotionally Focused Couple Therapy With Neurodegenerative Diseases: A Pilot Study.
  
  The American Journal of Family Therapy
  
  ,
  
  45
  
  (1), 15–26.
  
  https://doi.org/10.1080/01926187.2016.1223562
  
• Horwitz, A. V., & Reinhard, S. C. (1995). Ethnic Differences in Caregiving Duties and Burdens Among Parents and Siblings of Persons with Severe Mental Illnesses.
  
  Journal of Health and Social Behavior
  
  ,
  
  36
  
  (2), 138.
  
  https://doi.org/10.2307/2137221
  
• LoBue, C., Woon, F. L., Rossetti, H. C., Hynan, L. S., Hart, J., & Cullum, C. M. (2018). Traumatic brain injury history and progression from mild cognitive impairment to Alzheimer disease.
  
  Neuropsychology
  
  ,
  
  32
  
  (4), 401–409.
  
  https://doi.org/10.1037/neu0000431
  
• Nilsson, L.-G. (2006). Memory Processes, Aging, Cognitive Decline, and Neurodegenerative Diseases.
  
  European Psychologist
  
  ,
  
  11
  
  (4), 304–311.
  
  https://doi.org/10.1027/1016-9040.11.4.304
  
• Smith, G. E. (2016). Healthy cognitive aging and dementia prevention.
  
  American Psychologist
  
  ,
  
  71
  
  (4), 268–275.
  
  https://doi.org/10.1037/a0040250
  
• Soril, L. J. J., Leggett, L. E., Lorenzetti, D. L., Silvius, J., Robertson, D., Mansell, L., … Clement, F. M. (2014). Effective Use of the Built Environment to Manage Behavioural and Psychological Symptoms of Dementia: A Systematic Review.
  
  PLoS ONE
  
  ,
  
  9
  
  (12), e115425.
  
  https://doi.org/10.1371/journal.pone.0115425
  

Abstract

Background

: Patients who receive radiation therapy for prostate cancer can experience erectile dysfunction.

Objective

: To find current research on interventions from radiation induced erectile dysfunction (RIED)

Methods

: A literature review was conducted to analyze available interventions for prostate cancer patients who received radiation therapy. All sources were reviewed to obtain information on available interventions relating to RIED in prostate cancer patents.

Results

: There are several options available for patients experiencing REID. The two most common interventions used are Sildenafil and Tadalafil, which are Phosphodiesterase type 5 inhibitors (PDE5I). Both have been proven effective and are relatively low risk. Therapy, an alternative to medication, has also been theorized to improve erectile dysfunction by easing post-treatment anxiety and depression.

Conclusion

: PDE5Is have data supporting their effectiveness and relatively low side effects. If one PDE5I, such as Sildenafil, causes unmanageable side effects Tadalafil could be better for those patients. Some data supports therapy as an option, but no research studies have been found on the therapy model in this review of literature.

Introduction

In some cases, radiation therapy is not only a blessing but also a curse. This is often the case for men who receive radiation for prostate cancer. Throughout their treatment, penile tissue and nerves can become damaged resulting in radiation-induced erectile dysfunction (RIED). They are given more years of their life to live but with a costly side effect. RIED can be very traumatic for the patient, decreasing their long-term quality of life. Currently, Phosphodiesterase type 5 inhibitors (PDE5I) are the primary medication used to RIED and the main two are Sildenafil and Tadalafil. Both are relatively safe but do have some risks associated with them. Along with radiation directly causing erectile dysfunction, anxiety and depression related to radiation treatment may also be the cause. Some researches created a therapy model that can be successful in helping patients with anxiety and depression caused erectile dysfunction.

Methods

Methods used to research literature relating to RIED was primarily with EBSCOhost through the University of Wisconsin-La Crosse library. Secondly, some sources used came from google scholar, but only articles that were free to everyone.  Some of the original research was not within the last five years but there were studies that reviewed them recently. The terms I used to search in EBSCOhost and google scholar were: “radiation therapy, erectile dysfunction, counseling, sildenafil, and Tadalafil.”

Review of Literature

Radiation induced erectile dysfunction (RIED) is a side effect many prostate patients encounter as a result of radiation therapy. Since RIED are caused by different factors, there are different strategies used to manage it.1 Sildenafil, or more commonly known as Viagra is one mode of intervention that can be utilized by patients who encounter RIED. Sildenafil is a PDE5I and works by preventing the degradation of cyclic guanosine monophosphate (cGMP) in the penile tissue.1,2 Sildenafil causes vascular dilation in penile tissue, resulting in a response to sexual stimulation1,2 Having options for prostate cancer patients gives them hope as they battle treatment side effects of pelvic radiation. According to Incrocci,1 the effects Sildenafil had from a double-blind study showed there is an increase of sexual function in 55 percent of patients. Incrocci1 shows that this is a viable treatment option for men experiencing RIED and it can help them to regain sexual function. Since the cause of RIED cannot be narrowed down to only one type of tissue that was damaged from prostate radiation treatment, this drug is not going to work for everyone. Another way radiation can disrupt the process of gaining an erection is damage to the cavernous nerves that are located in close proximity to the prostate.1-3 As a result of the complicated nature of gaining an erection, Incrocci1 shows that 24 out of the 60 participants in the double-blind study continued to have success with sildenafil after two years. However, 36 participants reported that they stopped taking sildenafil because they did not see the desired results.1 This treatment did not work for most of the patients, but it is still a good treatment option because the side effects from Sildenafil are minimal.

According to Incrocci1, 16 percent of those participating in the double-blind study stopped taking the medication specifically as a result of side effects. Side effects have a relatively low occurrence, but it is still a factor that needs to be considered. In a study conducted by Taylor et al.4, 128 men were prescribed sildenafil with an average age of 58.7. Of the 128 men, the most common side effects experienced were headaches, flushing, and dyspepsia which occurred in 16 men, 14 men, and 6 men respectively.4 However, sildenafil’s half-life is four hours and these symptoms were short lived resulting in only three percent of men exhibited side effects after 12 hours.4 Sildenafil is shown to be safe for patients to take with relatively insignificant side effects. In addition, even if the side effects are present, they are short lived in many patients which makes it an option for patients to try and decide if it is beneficial to them.

Another PDE5I drug used in the treatment of erectile dysfunction is Tadalafil. Tadalafil and Sildenafil both work by the same mechanism, however, Tadalafil has a much longer lasting effect in the body.5 In a study conducted by Choi et al.5, 180 men with erectile dysfunction were enrolled in a trial testing the usefulness and side effects of Tadalafil. However, only 120 men completed the 12-week trial.5 These men were separated into two groups. One group received 5mg every day and the second group received 5mg every other day.5 As a result of this trial, there was no significant difference between the two groups in relation to return of erectile function. Effectiveness of Tadalafil was analyzed using the international index of erectile function which includes 15 questions long relating to their sexual function. As a result of this trial, Tadalafil increased the average score of all participants from 13.4 to 18.7.5 Tadalafil has shown to be an effective method to overcome erectile dysfunction that prostate patients experience as a result of radiation therapy.

Tadalafil is also useful in its flexibility of when it is taken and when the erectile function is received. Tadalafil has a much longer half-life when compared to Sildenafil, 17.5 hours and four hours respectively.4,5 As a result, men who use Tadalafil are able to have erectile function up to 36 hours after taking the medication.4,5 In addition to having a long lasting effect on erectile function, there is also a quick response to when Tadalafil is first taken. This medication can have an effect on the body within 16 minutes for some men.4 This flexible schedule can make it easier for men because it does not require as much planning. Another result of its long half-life is its duration of side effects. The side effects last much longer with Tadalafil than they do with Sildenafil. In the study conducted by Taylor et al.4, 24 of the 214 men who received Tadalafil, reported having experienced headaches. In addition, 11 men experienced dyspepsia and four men experienced flushing.4

Another option that is available for patients is therapy. It is a resource that not many people consider but it is a risk-free intervention to try. As patients go through the cancer treatment process for radiation therapy, they experience a lot of fears and emotions. One meta-analysis of 4494 patients reported high anxiety and depression rates which were 15.09 percent and 15.06 percent respectively.5 As a result, these patients could be facing phycological instances of erectile dysfunction and could benefit from a treatment option that does not include medication with additional side effects. Men undergoing prostate cancer treatment can hear the words erectile dysfunction and automatically have anxiety, which actually induces it. One research group produced a model that they think would help resolve some of the erectile dysfunction symptoms related to anxiety. According to Kimmes et al.7, the most important parts of this treatment is to be sex positive and practice mindfulness. Mindfulness is important because it does not ignore the problem but instead brings it to light in a nonjudgmental way.7 The therapy model is completed in three levels and the first one consists of just meeting the couple and evaluating out the situation.7 This is a way to find out what the couples needs are and dialog to become comfortable talking about this subject together.7 The middle level is focused on the male becoming comfortable and mindful of the situation.7 The last level is for the couple to talk about ways to reduce anxiety together and reward each other for mindful thinking by doing something nice for them.7 For example, one could do all the laundry that day as a nice gesture of their appreciation. After these levels, the couple should feel more comfortable with each other, which will lower their anxiety level and potentially improving erectile dysfunction.

Conclusion

As a result from current literature on RIED, there are interventions available for prostate patients who experience RIED with relatively low side effects.1,4 Some medications might not work for everyone but there is a relatively small risk in trying them out. It is still important for men with RIED to talk with their doctor to find what is right for them. There is an abundance of research showing PDE5Is can help solve ED. There is not a lot recent research though, which could mean it is accepted in present day medicine as being effective. Therapy can also help some patients who are experiencing erectile dysfunction and need to get by some mental barriers to help. For example, a lot of patients experience anxiety and depression going though treatment, which can cause erectile dysfunction by themselves.7 The sources I found that covered therapy and erectile dysfunction did not have much data showing their theory would work.7 They had data showing that it could work but did not actually study a group a couples going through the therapy. I think it would be beneficial for someone to create a research study on the therapy plan I talked about in order to quantify if it would work in practice.

References

1. Incrocci L. Radiotherapy for prostate cancer and sexual health.
   
   Transl Androl Urol
   
   . 2015;4(2):124–130.
   
   doi:10.3978/j.issn.2223-4683.2014.12.08
   
   . Published April 4, 2015. Accessed October 9, 2019.
2. Albaugh J. 50 years of erectile dysfunction: How far have we come?
   
   Urologic Nursing
   
   . 2019;39(5):262-264.
   
   doi:10.7257/1053-816X.2019.39.5.262
   
   . Published September 1, 2019. Accessed October 9, 2019.
3. Voznesensky M, Annam K, Kreder K. Understanding and managing erectile dysfunction in patients treated for cancer.
   
   Journal of Oncology Practice
   
   . 2016 Jun;12(6):596. 2016;12(4):297–304.
   
   doi:10.1200/JOP.2016.010678
   
   . Published September 21, 2016. Accessed October 9, 2019.
4. Taylor J, Baldo O, Storey A, Cartledge J, Eardley I. Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors.
   
   BJU International
   
   . 2009;103(10):1392-1395.
   
   doi:10.1111/j.1464-410X.2008.08328.x.
   
   Published April 27, 2009. Accessed October 9, 2019.
5. Choi H, Kim J-H, Shim J-S, et al. Comparison of the efficacy and safety of 5-mg once-daily versus 5-mg alternate-day tadalafil in men with erectile dysfunction and lower urinary tract symptoms.
   
   International Journal of Impotence Research
   
   . 2015;27(1):33-37.
   
   doi:10.1038/ijir.2014.19.
   
   Published July 3, 2014. Accessed October 9, 2019.
6. Watts S, Leydon G, Birch B, et al. Depression and anxiety in prostate cancer: A systematic review and meta-analysis of prevalence rates.
   
   BMJ Open
   
   2014;4:e003901.
   
   doi:10.1136/bmjopen-2013-003901
   
   . Accessed October 9, 2019.
7. Kimmes JG, Mallory AB, Cameron C, Köse Ö. A treatment model for anxiety-related sexual dysfunctions using mindfulness meditation within a sex-positive framework.
   
   Sexual & Relationship Therapy
   
   . 2015;30(2):286-296.
   
   doi:10.1080/14681994.2015.1013023
   
   . Published February 23, 2019. Accessed October 9, 2019.