{"id":160,"date":"2020-11-19T04:40:09","date_gmt":"2020-11-19T09:40:09","guid":{"rendered":"https:\/\/on-linelearning.ca\/sherrimelrosepublications\/chapter\/late-life-depression-nursing-actions-that-can-help\/"},"modified":"2020-11-19T04:40:09","modified_gmt":"2020-11-19T09:40:09","slug":"late-life-depression-nursing-actions-that-can-help","status":"publish","type":"chapter","link":"https:\/\/on-linelearning.ca\/sherrimelrosepublications\/chapter\/late-life-depression-nursing-actions-that-can-help\/","title":{"raw":"Late life depression: nursing actions that can help","rendered":"Late life depression: nursing actions that can help"},"content":{"raw":"\n[caption id=\"attachment_1621\" align=\"alignnone\" width=\"183\"]\"Late<\/a> [PDF - 315 KB][\/caption]\n
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Citation<\/p>\n\n<\/header>\n

\n\nMelrose S. (2018). Late life depression: Nursing actions that can help. Perspectives in Psychiatric Care, 55(3), 453-458<\/em>. https:\/\/doi.org\/10.1111\/ppc.12341\n\n<\/div>\n<\/div>\n
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Abstract<\/p>\n\n<\/header>\n

Purpose:<\/strong> This article explains the symptoms of late life depression (LLD) and discusses evidence-informed actions that nurses can implement to provide older adults with the help they need.\nConclusions:<\/strong> Recognizing and addressing depression in older adults can enhance quality of life.\nPractice Implications:<\/strong> People with LLD may not appear sad or express feelings of depression. Instead, they demonstrate loss of interest, frailty, cognitive impairment, suicidal ideation, unexplained somatic complaints, and loneliness. Documenting symptoms, screening, and assessing suicidal ideation are essential. Positive outcomes are associated with antidepressant medications, cognitive behavioral therapy, electroconvulsive therapy, neuromodulation therapies, and exercise.\nKeywords<\/strong>\nlate life depression, LLD, nursing care for older adults<\/div>\n<\/div>\n

1     | INTRODUCTION<\/h1>\nLate life depression (LLD) is the occurrence of a major depressive disorder in adults aged 60 years or older.1<\/sup> When symptoms that do not meet major depressive disorder criteria are also considered, subsyndromal depressive disorders and clinically significant symptoms of depression in later life are estimated to affect between 0.9% and 49.0% of adults aged 65 years or older.2\u20134<\/sup> As many as 17% of adults over 75; 25% of adults over 85; and 49% of adults over 90 are affected by at least some symptoms of depression.2,5<\/sup>\n\nLLD is associated with cognitive impairment, increased morbidity and mortality from co\u2010occurring medical illness, increased death by suicide as well as increased health care utilization and cost.1,3,6<\/sup> Depression in older adults is often undetected or inadequately treated.7\u201313<\/sup> Existing literature has focused on providing physicians with information related to diagnosing and treating LLD. However, nurses in a variety of practice areas also encounter many older adults who are struggling to cope with symptoms of depression. Psychiatric and mental health nurses are well positioned to provide these nurse peers with a deeper understanding of the complexities of the condition. When nurses recognize LLD and implement evidence\u2010informed care, they are better able to support the older adults in their care toward an improved quality of life. This article presents an explanation of LLD and suggests nursing actions that can help.\n

2     | TOWARD AN EXPLANATION OF LLD<\/h1>\nPeople experience depression later in their lives in different ways and for a variety of different reasons. Explanations of LLD are seldom straightforward. LLD is generally explained as depression that occurs after the age of 60 years, although onset and definition of cutoff may vary.14<\/sup> Presentations of LLD can include reoccurrence of a previous depression, termed early onset depression; a mood disorder secondary to a general medical condition; a depressed mood secondary to a substance or medication use (including polypharmacy); or as a new\u2010onset depression, later in life, termed late\u2010onset depression (LOD).5<\/sup> As many as half of the cases of LLD are late onset and are occurring among people who have not previously experienced clinically significant symptoms of depression.15<\/sup> In this article, the term LLD will refer to LOD. Unless otherwise specified, the information presented can be considered relevant to the care of older people experiencing any form of depression.\n\nBoth the diagnosis of major depressive disorder (MDD) and the presence of subsyndromal or clinically significant depressive symptoms are associated with LLD.15<\/sup> According to the Diagnostic and<\/em> Statistical Manual of Mental Disorders<\/em>, 5th edition (DSM\u20105),16<\/sup> to receive a diagnosis of MDD, an individual must exhibit symptoms of depressed mood and\/or loss of interest plus four or more associated symptoms, including changes in appetite, sleep disturbance, psychomotor agitation or retardation, fatigue, inappropriate guilt or feelings of worthlessness, poor concentration or indecisiveness, and recurrent thoughts of death or suicidal ideation. Symptoms must be present nearly every day for at least two weeks and cause clinically significant distress or functional impairment.16<\/sup>\n\nHowever, in older adults, the two core symptoms of MDD, depressed mood (sadness or dysphoria) and loss of interest in activities once found pleasurable (anhedonia) can differ from those seen in younger people.17<\/sup> The affective symptom of a \u201cdepressed mood\u201d can actually be absent in some older adults who are suffering from depression. Rather, a lack of sadness or dysphoria, known as depression without sadness, <\/em>where mood does not appear sad is common.18\u201320<\/sup> Similarly, rather than clear indications of sadness, symptoms like lack of vigor, apathy, and withdrawal<\/em>, known as \u201cdepletion syndrome\u201d are apparent.19<\/sup>\n\nIn contrast, the second MDD core symptom of \u201closs of interest\u201d is usually pronounced in LLD.17<\/sup> Clinicians, family members, and older adults themselves may inadvertently view anhedonia more as a part of normal aging than as a critical indicator of depression.9<\/sup> It can inaccurately be perceived as an understandable reaction to limitations imposed by medical conditions; retirement; death of a partner; decreasing social contacts; and lifestyle changes, such as moving to a care facility.10<\/sup>\n\nFurther, the additional MDD symptoms of changes in appetite, sleep disturbance, psychomotor agitation or retardation, fatigue, inappropriate guilt or feelings of worthlessness, poor concentration or indecisiveness, and recurrent thoughts of death or suicidal ideation can be overlooked in LDD. Loss of appetite <\/em>and weight loss, a common and important symptom of LLD, is also associated with cognitive deficits21<\/sup> and can predict an increased likelihood of developing dementia.22<\/sup> Sleep disturbances, particularly early morning<\/em> awakenings<\/em>, are present in most cases of LLD and are predictive of a poor prognosis and future depressive episodes.3,23<\/sup>\n\nPsychomotor retardation more so than psychomotor agitation is common in LLD.5<\/sup> Although some slowing is not unexpected in normal aging, psychomotor retardation, such as disturbances in speech, facial expression, fine motor behavior, and gross locomotor activity (especially a decreased walking speed<\/em>) are more apparent in people with LLD.24<\/sup> Fatigue is often experienced as a physical tiring <\/em>and lack of energy rather than as a mental fatigue.25<\/sup> It is important to note that symptoms of frailty <\/em>(including loss of interest, weight loss, psychomotor slowing, and physical tiring) overlap with symptoms of LLD and are frequently associated with comorbid medical concerns.25<\/sup>\n\nInappropriate guilt or feelings of worthlessness are less frequent in older adults than in young people.20,26<\/sup> By contrast, there is often actual impairment in peoples\u2019 ability to concentrate and make decisions.20<\/sup> Further, compounding any assessment of how poor concentration and indecisiveness might be linked to depression is the question of whether medical conditions are causing disturbances in thinking and slowing information processing abilities.6<\/sup> In LLD, the depressive symptom of \u201cpoor concentration\u201d could be manifested more as memory loss <\/em>or cognitive impairment with executive<\/em> dysfunction <\/em>(a clinical expression of frontostriatal abnormalities where the brain is less able to control cognitive processes, such as carrying out tasks).27<\/sup> The cognitive impairments in LLD mimic symptoms of dementia.27<\/sup>\n\nThis cognitive impairment also makes people with LLD at high risk of death by suicide.28 Symptoms of recurrent thoughts of death or suicidal ideation <\/em>in LLD are especially concerning. Older adults can act on their suicidal ideation with more serious intent, less warning, and more lethality than younger populations.29<\/sup> Signs that indicate impending suicide include feelings of hopelessness or lack of purpose, feeling trapped, talking about death, preparing for suicide, social withdrawal, increased substance use, and reckless behavior.6<\/sup> Factors believed to provide some protection against acting on suicidal thoughts include social connectedness, spirituality, religious beliefs, and cultural attitudes against suicide.6<\/sup>\n\nFor older adults, particularly those living with physical illnesses, increasing somatic complaints <\/em>more so than typical symptoms of MDD are highly suggestive of LLD.30,31<\/sup> Persistent complaints of pain, headache, fatigue, insomnia, gastrointestinal distress; unexplained delayed recoveries after surgery; and failure to thrive in institutional settings can be linked to depression.31<\/sup> For people with cerebrovascular disease, any microdamage occurring in the small vessels compromises the ability of the frontal\u2010subcortical circuits to regulate mood, resulting in a depression known as vascular or subcortical ischemic depression.32,33<\/sup> Higher rates of LLD occur in people living with heart disease, diabetes, asthma, and arthritis.12<\/sup> While it is understandable that people will experience distress caused by their physical illnesses, it is important to emphasize that unexplained somatic complaints are indicative of LLD.\n\nFinally, people experiencing loneliness<\/em>, or feeling as though they do not belong, are susceptible to LLD.34\u201336<\/sup> Studies indicate that between 5% and 10% of people between the ages of 60 and 80; and between 40% and 50% of people over 80 reported feeling lonely frequently.37<\/sup> Those at greatest risk of experiencing loneliness are women, particularly those who are older; and people who are without partners, are financially insecure and are physically unwell.37<\/sup> As many as 87% of older adults with depressive symptoms reported co\u2010occurring feelings of loneliness.36<\/sup> Loneliness has been found to exacerbate depressive symptoms, decrease quality of life, and leave older adults feeling as though they have no control over their situation.36<\/sup>\n\nIn his seminal commentary on depression in later life, Dan Blazer urged clinicians not to limit their assessment of LLD to diagnostic categories of depression, but rather to include depressive symptoms that do not fully meet the criteria but nonetheless cause significant distress.20<\/sup> As the preceding discussion explained, older adults with symptoms of depression without sadness, lack of vigor, apathy and withdrawal, loss of interest, loss of appetite, early morning awakenings, decreased walking speed, physical tiring, frailty, memory loss or cognitive impairment with executive dysfunction, suicidal ideation, somatic complaints, and loneliness could be suffering from LDD. Recognizing and addressing these symptoms can decrease depression and functional impairment and enhance quality of life for older adults.38<\/sup> Next, actions that nurses can implement when they encounter the many older adults who are struggling with depression are suggested.\n

3    | PRACTICE IMPLICATIONS: ACTIONS THAT CAN HELP<\/h1>\n

3.1     | Document symptoms of LLD<\/h2>\nRecognizing and documenting the aforementioned symptoms of LLD is a critical first step in helping people receive treatment for depression. Knowing that depressed older adults are more likely to present with loss of interest and unexplained somatic complaints than with a sad mood or self-identified complaints of depression, clinicians must intentionally inquire about LLD and maintain ongoing documentation. Seeking out information about any changes in lifestyle, social withdrawal, and feelings of loneliness from family members should also be included. Typical open ended interview questions that assess history, mental status, and level of cognitive and functional capacities should be followed by more directed questions specific to LLD.6<\/sup>\n

3.2     | Screen with the Patient Health Questionaire\u20109<\/h2>\nGiven the prevalence, impact and difficulties inherent in recognizing LLD, screening instruments can supplement interview findings and provide the objective data needed to indicate the risk or presence of depression in older adults.39<\/sup> The 9\u2010item Patient Health Questionnaire (PHQ\u20109), developed by Kroenke et al.40<\/sup> provides reliable, valid detection of depression in LLD.6,10,38,39<\/sup> The PHQ\u20109 is self\u2010administered, requires about 5 minutes to complete, is easily scored and interpreted, and is available for free.40<\/sup> The short questionnaire incorporates DSM\u20105 depression diagnostic criteria, as well as clinically significant depressive symptoms; rates the frequency of the symptoms and factors these into the scoring severity index; screens for suicidal ideation; and assigns weight to the depressive symptoms that impact how people function.40<\/sup> The PHQ\u20109 can be administered in a variety of settings both as an initial screening instrument and to follow up and evaluate interventions.10,38<\/sup>\n

3.3     | Assess suicide risk<\/h2>\nAs with any depressive illness, suicidal ideation means that protective factors must be assessed in people who may be experiencing LLD. Suicidal ideation can range from thinking passively about death and wishing to die, to active thoughts of self\u2010harm, plans, and an intention to die.6<\/sup> In older adults, means can include but are not limited to, hanging, firearms, poisoning, and hoarding medications.6<\/sup> Posing the question: \u201cWhat stops you?\u201d opens the door for people to express protective factors that are unique to their situation. Clearly, ongoing assessment, documentation, and immediate reporting of suicidal ideation must be implemented when LLD is or could be present.\n

3.4    | Pharmacological treatment<\/h2>\nSelective serotonin reuptake inhibitors (SSRIs) are the most common first\u2010line treatment for LLD.1,41<\/sup> The SSRI\u2010Sertraline (Zoloft), has a favorable side\u2010effect profile and can be taken by people with a history of cognitive impairment and stroke.41<\/sup> When SSRIs are contraindicated, alternative classes of antidepressants, such as Mirtazapine (Remeron), demonstrate good efficacy in older adults.41<\/sup> The side effects of Mirtazapine, which include sedation and weight gain, can have therapeutic benefit to the difficulty in sleeping and loss of appetite so commonly experienced in LLD. Tricyclic antidepressants, in particular, Nortriptyline (Allegron, Aventyl), can also be effective in older adults who do not have cardiac conditions or cognitive impairment.41<\/sup>\n\nAntidepressant medications are usually trialed for approximately 6 weeks; should not be withdrawn abruptly and can be expected to be taken for at least 2 years.41<\/sup> However, it is important to note that as many as one\u2010third of older adults will not respond to antidepressant treatment; relapse rates for those who do respond are high; and the approach is less efficacious than for younger people.13,42<\/sup>\n

3.5     | Psychological treatment<\/h2>\nPsychological treatments, particularly when implemented in combination with pharmacological treatments have demonstrated moderate efficacy for some older adults.31,42,43<\/sup> Cognitive behavioral therapy (CBT), problem\u2010solving therapy (PST), interpersonal therapy (IPT), and reminiscence and life review therapy (RLRT) have been successfully implemented.43,44<\/sup> In CBT, people identify and challenge distorted thinking; in PST, people identify problems, brainstorm solutions, implement a solution, and then evaluate its effectiveness; in IPT, people explore feelings and ways to change behavior in relation to interpersonal relationships, including grief and role transitions; and in RLRT people review positive life events to enhance wellbeing.43<\/sup>\n\nAlthough therapies such as CBT, PST, and IPT are implemented by trained therapists, adaptions of RLRT and approaches to celebrating positive life events, both past and present, can readily be adapted in settings where nurses provide support to older adults. Similarly, behavioral activation (BA) therapy, which seeks to create a personal environment of positive reinforcement by increasing functional and pleasurable behavior, and by decreasing avoidant and depressed behavior, uses less complex protocols, and has successfully been implemented by mental health nurses.45<\/sup> Many older adults, especially those who are over 75 and are experiencing depression for the first time, prefer not to talk about their depression and do not view pharmacological and psychological treatments as likely to be helpful.11<\/sup> Therefore, exploring people\u2019s own ideas about the depression they are experiencing and the solutions they believe are valuable is foundational to any treatment approach.\n

3.6     | Electroconvulsive therapy<\/h2>\nElectroconvulsive therapy (ECT) can also be effective in treating LLD.7<\/sup> People who will benefit most from ECT are those with depression that is resistant to other treatments and for those at risk of serious harm because of psychotic depression, suicidal ideation, or severe malnutrition.46<\/sup> Although cardiovascular and cognitive side effects can occur with older adults, deleterious effects of ECT in LLD are usually limited and transient, with better cognitive outcomes with unilateral ECT.47<\/sup>\n\nIn one study, when elderly people with unipolar depression were treated twice weekly with right unilateral ECT, their cognition, psychomotor agitation, and psychomotor retardation improved significantly.48<\/sup> This improvement was attributed to a significant gray matter volume increase, which was most pronounced on the side receiving neurostimulation.48<\/sup> Common side effects of ECT that nurses must monitor include headache that usually responds to analgesics, temporary confusion or memory impairment, and falls immediately after treatment sessions.46<\/sup>\n

3.7     | Neuromodulation therapies<\/h2>\nAlternative neuromodulation therapies also provide neurostimulation, but unlike ECT, these therapies do not require anesthetic and have reduced side effects, making them safer for older adults with comorbid medical conditions.49<\/sup> Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct\u2010current stimulation (tDCS) modulate cerebral activity using brain stimulation and are usually implemented over a 4 to 6 week period.50<\/sup> In older adults with nonpsychotic depression, rTMS is well tolerated but higher intensities and greater numbers of treatments may be needed than for younger people.50<\/sup> Beyond its positive effects on mood, tDCS may also have positive effects on cognition.50<\/sup>\n

3.8     | Physical exercise<\/h2>\nPhysical exercise programs can improve outcomes with some symptoms of LLD. In combination with antidepressant medication, exercise programs for older adults that included brief intervals of increased workload were found to decrease symptoms of depressed mood and psychomotor retardation.51<\/sup> Aerobic activities, which stimulate and sustain heart and breathing rates, improved cognition and reduced disability in depressed older adults.52<\/sup>\n\nWhen high intensity progressive resistance training was integrated into exercise programs, participants\u2019 sleep quality improved.53<\/sup> Knowing that sleep disturbances are frequently\npresent in LLD,3,23<\/sup> the value of integrating resistance training into older adults\u2019 physical activities becomes clear. Weekly group exercise programs of 3 \u00d7 50 minute sessions, which included\nmoderate cardiovascular exercise, such as walking with waving or clapping hands to music for a duration of 30 minutes, improved quality of life and perceived social support.54<\/sup> Exergames or\nentertaining video games that combined game play with exercise decreased subsyndromal symptoms of depression55,56<\/sup> and improved balance and mobility.55<\/sup>\n\nIn community settings, nurses can encourage older adults to participate in seniors\u2019 fitness activities in their area. In institutional settings, they can advocate for the creation of fitness programs that personalize physical exercise for patients\/residents. Although medical conditions can impose limitations on peoples\u2019 mobility, engaging in some form of daily physical exercise can make an important difference in mood.\n\n \n

3.9     | Lifestyle modifications<\/h2>\nIn addition to increasing physical exercise, lifestyle modifications, such as improving dietary patterns and addressing vitamin D deficiencies may also exert a positive influence on some symptoms of depression. Emerging evidence suggests that modifying dietary patterns may reduce the risk of developing depression.57<\/sup> Actions that can help include: following the Mediterranean diet; increasing consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; including a high consumption of foods rich in omega\u20103 polyunsaturated fatty acids; replacing unhealthy foods with wholesome nutritious foods; and limiting intake of processed foods, \u201cfast\u201d foods, commercial bakery goods, and sweets.57<\/sup>\n\nAlthough causal links between vitamin D deficiency and the development of depression have not been established, studies reveal that vitamin D deficiency accompanies late\u2010life depression.58<\/sup> For older adults, the skin capacity to synthesize vitamin D from sunlight can be reduced as much as 25%, increasing the likelihood of vitamin D deficiency.58<\/sup> Those who have limited opportunities to be outdoors or to be exposed to sunlight are particularly at risk. The 25\u2010hydroxy vitamin D blood test indicates that vitamin D deficiency exists when levels are less than 12.5 ng\/mL.59<\/sup> Vitamin D supplements may be helpful.\n

4 | CONCLUSION<\/h1>\nAdults over 60 can experience symptoms of depression somewhat differently than younger people. Older adults living with LLD may not appear sad or express feelings of depression. Instead, they may demonstrate loss of interest, frailty, cognitive impairment, suicidal ideation, unexplained somatic complaints, and loneliness. In response, nurses should document these symptoms, screen with the PAQ\u20109 and, importantly, assess for suicidal ideation. Antidepressant medications, CBT, electroconvulsive therapy, neuromodulation therapies, physical exercise, and lifestyle modifications can bring needed support and relief to the increasing number of people burdened with LLD.\n

CONFLICTS OF INTEREST<\/h1>\nThe authors declare that there are no conflicts of interest.\n

ORCID<\/h1>\nSherri Melrose       <\/em>http:\/\/orcid.org\/0000-0002-2056-8547<\/a>\n

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  33. Van Agtmaal MJM, Houben AJHM, Pouwer F, Stehouwer CDA, Schram MT. Association of microvascular dysfunction with late\u2010life depression: a systematic review and meta\u2010analysis. JAMA<\/em> Psychiatry<\/em>. 2017;74(7):729\u2010 739. https:\/\/doi.org\/10.1001\/jamapsychiatry.2017.0984<\/a><\/li>\n \t
  34. Hegeman A, Schutter N, Comijs H, et al. Loneliness and cardiovascular disease and the role of late\u2010life depression. Int J Geriatr<\/em> Psychiatry<\/em>. 2018;33(1):e65\u2010e72. https:\/\/doi.org\/10.1002\/gps.4716<\/a><\/li>\n \t
  35. Holvast F, Burger H, de Waal MMW, van Marwijk HWJ, Comijs HC, Verhaak PFM. Research report: Loneliness is associated with poor prognosis in late\u2010life depression: longitudinal analysis of the Netherlands study of depression in older persons. J Affect Disord<\/em>. 2015;185:1851\u20101857. https:\/\/doi.org\/10.1016\/j.jad.2015.06.036<\/a><\/li>\n \t
  36. Van Beljouw IMJ, Van Exel E, De Jong Gierveld J, et al. \u201cBeing all alone makes me sad\u201d: loneliness in older adults with depressive symptoms. Int Psychogeriatr<\/em>. 2014;26(9):1541\u20101551. https:\/\/doi.org\/10.1017\/S1041610214000581<\/a><\/li>\n \t
  37. Hansen T, Slagsvold B. Late\u2010life loneliness in 11 European countries: results from the generations and gender survey. Soc Indic Res<\/em>. 2015;124(1):1\u201020.<\/li>\n \t
  38. Smith M, Stolder ME, Liu MF. Evaluation of an innovative late\u2010life depression training program. Perspect Psychiatr Care<\/em>. 2014;50:19\u201026. https:\/\/doi.org\/10.1111\/ppc.12019<\/a><\/li>\n \t
  39. Jones M. Using screening tools to identify the risk or presence of depression in older people. Nurs Times<\/em>. 2009;105:49\u201050. https:\/\/www.nursingtimes.net\/roles\/older\u2010people\u2010nurses\/using\u2010screening\u2010tools\u2010to\u2010identify\u2010the\u2010risk\u2010or\u2010presence\u2010of\u2010depression\u2010in\u2010older\u2010people\u2010\/5009615.article<\/a><\/li>\n \t
  40. Kroenke K, Spitzer RL, Williams JBW. The PHQ\u20109: validity of a brief depression severity measure. J Gen Intern Med<\/em>. 2001;16(9):606\u2010613. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1495268\/<\/a><\/li>\n \t
  41. Allan CL, Ebmeier KP. Review of treatment for late\u2010life depression. Adv Psychiatr Treat<\/em>. 2013;19:302\u2010309. https:\/\/doi.org\/10.1192\/apt.bp.112.010835<\/a><\/li>\n \t
  42. Knochel C, Alves G, Friedrichs B, et al. Treatment\u2010resistant late\u2010 life depression: challenges and perspectives. Curr<\/em> Neurophar<\/em>m<\/em>a<\/em>col<\/em>. 2015;13(5):577\u2010591. https:\/\/doi.org\/10.2174\/1570159X1305151013200032<\/a><\/li>\n \t
  43. Francis JL, Kumar A. Psychological treatment of late\u2010life depression. Psychiatr Clin North Am<\/em>. 2013;36:561\u2010575.<\/li>\n \t
  44. Holvast F, Massoudi B, Oude Voshaar RC, Verhaak PFM. Non\u2010 pharmacological treatment for depressed older patients in primary care: a systematic review and meta\u2010analysis. PLOS One<\/em>. 2017;12(9): e0184666. https:\/\/doi.org\/10.1371\/journal.pone.0184666<\/a><\/li>\n \t
  45. Janssen N, Huibers MJH, Lucassen P, et al. Behavioural activation by mental health nurses for late\u2010life depression in primary care: a randomized controlled trial. BMC Psychiatry<\/em>. 2017;17:230. https:\/\/doi.org\/10.1186\/s12888\u2010017\u20101388\u2010x<\/a><\/li>\n \t
  46. Un\u00fctzer J. Late\u2010life depression. N Engl J Med<\/em>. 2007;357(22):2269\u20102276.<\/li>\n \t
  47. Kumar S, Mulsant B, Liu A, et al. Systematic review of cognitive effects of electroconvulsive therapy in late\u2010life depression. Am<\/em> J Geriatr Psychiatry<\/em>. 2016;24(7):547\u2010565. https:\/\/doi.org\/10.1016\/j.jagp.2016.02.053<\/a><\/li>\n \t
  48. Bouckaert F, De Winter FL, Emsell L, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study. J Psychiatry Neurosci<\/em>. 2016;2):105\u2010114. https:\/\/doi.org\/10.1503\/jpn.140322<\/a><\/li>\n \t
  49. McDonald WM. Neuromodulation treatments for geriatric mood and cognitive disorders. Am J Geriatr Psychiatry<\/em>. 2016;24(12):1130\u20101141. https:\/\/doi.org\/10.1016\/j.jagp.2016.08.014<\/a><\/li>\n \t
  50. G\u00e1lvez V, Ho KA, Alonzo A, Martin D, George D, Loo CK. Neuromodulation therapies for geriatric depression. Curr Psychiatry<\/em> Rep<\/em>.   2015;17(7):59. https:\/\/doi.org\/10.1007\/s11920\u2010015\u20100592\u2010y<\/a><\/li>\n \t
  51. Murri MB, Ekkekakis P, Menchetti M, et al. Physical exercise for late\u2010life depression: effects on symptom dimensions and time course. J Affect<\/em> Disord<\/em>. 2018;230:65\u201070. https:\/\/doi.org\/10.1016\/j.jad.2018.01.004<\/a><\/li>\n \t
  52. Neviani F, Belvederi murri M, Mussi C, et al. Physical exercise for late life depression: effects on cognition and disability. In<\/em>t<\/em> Psychogeriatr<\/em>. 2017;29(7):1105\u20101112. https:\/\/doi.org\/10.1017\/S1041610217000576<\/a><\/li>\n \t
  53. Singh NA, Stavrinos TM, Scarbek Y, Galambos G, Liber C, Fiatarone Singh MA. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. J Gerontol A Biol Sci Med Sci<\/em>. 2006;60(6):768\u2010776.<\/li>\n \t
  54. Huang TT, Liu CB, Tsai YH, Chin YF, Wong CH. Physical fitness exercise versus cognitive behavior therapy on reducing the depressive symptoms among community\u2010dwelling elderly adults: a randomized controlled trial. Int J Nurs Stud<\/em>. 2015;52(10):1542\u20101552. https:\/\/doi.org\/10.1016\/j.ijnurstu.2015.05.013<\/a><\/li>\n \t
  55. Chao YY, Scherer YK, Montgomery CA, Wu YW, Lucke KT. Physical and psychosocial effects of Wii Fit exergames use in assisted living residents: a pilot study. Clin Nurs Res<\/em>. 2015;24(6):589\u2010603. https:\/\/doi.org\/10.1177\/1054773814562880<\/a><\/li>\n \t
  56. Rosenberg D, Depp CA, Vahia IV, et al. Exergames for subsyndromal depression in older adults: a pilot study of a novel intervention. Am J<\/em> Geriatr Psychiatry<\/em>. 2010;18(3):221\u2010226. https:\/\/doi.org\/10.1097\/JGP.0b013e3181c534b5<\/a><\/li>\n \t
  57. Opie RS, Itsiopoulos C, Parletta N, et al. Dietary recommendations for the prevention of depression. Nutr Neurosci<\/em>. 2017;20(3):161\u2010171. https:\/\/doi.org\/10.1179\/1476830515Y.0000000043<\/a><\/li>\n \t
  58. Jovanova O, Aarts N, Noordam R, Carola\u2010Zillikens M, Hofman A, Tiemeier H. Vitamin D serum levels are cross\u2010sectionally but not prospectively associated with late\u2010life depression. Acta Psychiatr<\/em> Scand<\/em>. 2017;135:185\u2010194. https:\/\/doi.org\/10.1111\/acps.12689<\/a><\/li>\n \t
  59. Manson JE, Brannon PM, Rosen CJ, Taylor CL. Vitamin D deficiency\u2014 is there really a pandemic? N Engl J Med<\/em>. 2016;375:1817\u20101820. https:\/\/doi.org\/10.1056\/NEJMp1608005<\/a><\/li>\n<\/ol>\n","rendered":"
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    Citation<\/p>\n<\/header>\n

    \n

    Melrose S. (2018). Late life depression: Nursing actions that can help. Perspectives in Psychiatric Care, 55(3), 453-458<\/em>. https:\/\/doi.org\/10.1111\/ppc.12341<\/p>\n<\/div>\n<\/div>\n

    \n
    \n

    Abstract<\/p>\n<\/header>\n

    Purpose:<\/strong> This article explains the symptoms of late life depression (LLD) and discusses evidence-informed actions that nurses can implement to provide older adults with the help they need.
    \nConclusions:<\/strong> Recognizing and addressing depression in older adults can enhance quality of life.
    \nPractice Implications:<\/strong> People with LLD may not appear sad or express feelings of depression. Instead, they demonstrate loss of interest, frailty, cognitive impairment, suicidal ideation, unexplained somatic complaints, and loneliness. Documenting symptoms, screening, and assessing suicidal ideation are essential. Positive outcomes are associated with antidepressant medications, cognitive behavioral therapy, electroconvulsive therapy, neuromodulation therapies, and exercise.
    \nKeywords<\/strong>
    \nlate life depression, LLD, nursing care for older adults<\/div>\n<\/div>\n

    1     | INTRODUCTION<\/h1>\n

    Late life depression (LLD) is the occurrence of a major depressive disorder in adults aged 60 years or older.1<\/sup> When symptoms that do not meet major depressive disorder criteria are also considered, subsyndromal depressive disorders and clinically significant symptoms of depression in later life are estimated to affect between 0.9% and 49.0% of adults aged 65 years or older.2\u20134<\/sup> As many as 17% of adults over 75; 25% of adults over 85; and 49% of adults over 90 are affected by at least some symptoms of depression.2,5<\/sup><\/p>\n

    LLD is associated with cognitive impairment, increased morbidity and mortality from co\u2010occurring medical illness, increased death by suicide as well as increased health care utilization and cost.1,3,6<\/sup> Depression in older adults is often undetected or inadequately treated.7\u201313<\/sup> Existing literature has focused on providing physicians with information related to diagnosing and treating LLD. However, nurses in a variety of practice areas also encounter many older adults who are struggling to cope with symptoms of depression. Psychiatric and mental health nurses are well positioned to provide these nurse peers with a deeper understanding of the complexities of the condition. When nurses recognize LLD and implement evidence\u2010informed care, they are better able to support the older adults in their care toward an improved quality of life. This article presents an explanation of LLD and suggests nursing actions that can help.<\/p>\n

    2     | TOWARD AN EXPLANATION OF LLD<\/h1>\n

    People experience depression later in their lives in different ways and for a variety of different reasons. Explanations of LLD are seldom straightforward. LLD is generally explained as depression that occurs after the age of 60 years, although onset and definition of cutoff may vary.14<\/sup> Presentations of LLD can include reoccurrence of a previous depression, termed early onset depression; a mood disorder secondary to a general medical condition; a depressed mood secondary to a substance or medication use (including polypharmacy); or as a new\u2010onset depression, later in life, termed late\u2010onset depression (LOD).5<\/sup> As many as half of the cases of LLD are late onset and are occurring among people who have not previously experienced clinically significant symptoms of depression.15<\/sup> In this article, the term LLD will refer to LOD. Unless otherwise specified, the information presented can be considered relevant to the care of older people experiencing any form of depression.<\/p>\n

    Both the diagnosis of major depressive disorder (MDD) and the presence of subsyndromal or clinically significant depressive symptoms are associated with LLD.15<\/sup> According to the Diagnostic and<\/em> Statistical Manual of Mental Disorders<\/em>, 5th edition (DSM\u20105),16<\/sup> to receive a diagnosis of MDD, an individual must exhibit symptoms of depressed mood and\/or loss of interest plus four or more associated symptoms, including changes in appetite, sleep disturbance, psychomotor agitation or retardation, fatigue, inappropriate guilt or feelings of worthlessness, poor concentration or indecisiveness, and recurrent thoughts of death or suicidal ideation. Symptoms must be present nearly every day for at least two weeks and cause clinically significant distress or functional impairment.16<\/sup><\/p>\n

    However, in older adults, the two core symptoms of MDD, depressed mood (sadness or dysphoria) and loss of interest in activities once found pleasurable (anhedonia) can differ from those seen in younger people.17<\/sup> The affective symptom of a \u201cdepressed mood\u201d can actually be absent in some older adults who are suffering from depression. Rather, a lack of sadness or dysphoria, known as depression without sadness, <\/em>where mood does not appear sad is common.18\u201320<\/sup> Similarly, rather than clear indications of sadness, symptoms like lack of vigor, apathy, and withdrawal<\/em>, known as \u201cdepletion syndrome\u201d are apparent.19<\/sup><\/p>\n

    In contrast, the second MDD core symptom of \u201closs of interest\u201d is usually pronounced in LLD.17<\/sup> Clinicians, family members, and older adults themselves may inadvertently view anhedonia more as a part of normal aging than as a critical indicator of depression.9<\/sup> It can inaccurately be perceived as an understandable reaction to limitations imposed by medical conditions; retirement; death of a partner; decreasing social contacts; and lifestyle changes, such as moving to a care facility.10<\/sup><\/p>\n

    Further, the additional MDD symptoms of changes in appetite, sleep disturbance, psychomotor agitation or retardation, fatigue, inappropriate guilt or feelings of worthlessness, poor concentration or indecisiveness, and recurrent thoughts of death or suicidal ideation can be overlooked in LDD. Loss of appetite <\/em>and weight loss, a common and important symptom of LLD, is also associated with cognitive deficits21<\/sup> and can predict an increased likelihood of developing dementia.22<\/sup> Sleep disturbances, particularly early morning<\/em> awakenings<\/em>, are present in most cases of LLD and are predictive of a poor prognosis and future depressive episodes.3,23<\/sup><\/p>\n

    Psychomotor retardation more so than psychomotor agitation is common in LLD.5<\/sup> Although some slowing is not unexpected in normal aging, psychomotor retardation, such as disturbances in speech, facial expression, fine motor behavior, and gross locomotor activity (especially a decreased walking speed<\/em>) are more apparent in people with LLD.24<\/sup> Fatigue is often experienced as a physical tiring <\/em>and lack of energy rather than as a mental fatigue.25<\/sup> It is important to note that symptoms of frailty <\/em>(including loss of interest, weight loss, psychomotor slowing, and physical tiring) overlap with symptoms of LLD and are frequently associated with comorbid medical concerns.25<\/sup><\/p>\n

    Inappropriate guilt or feelings of worthlessness are less frequent in older adults than in young people.20,26<\/sup> By contrast, there is often actual impairment in peoples\u2019 ability to concentrate and make decisions.20<\/sup> Further, compounding any assessment of how poor concentration and indecisiveness might be linked to depression is the question of whether medical conditions are causing disturbances in thinking and slowing information processing abilities.6<\/sup> In LLD, the depressive symptom of \u201cpoor concentration\u201d could be manifested more as memory loss <\/em>or cognitive impairment with executive<\/em> dysfunction <\/em>(a clinical expression of frontostriatal abnormalities where the brain is less able to control cognitive processes, such as carrying out tasks).27<\/sup> The cognitive impairments in LLD mimic symptoms of dementia.27<\/sup><\/p>\n

    This cognitive impairment also makes people with LLD at high risk of death by suicide.28 Symptoms of recurrent thoughts of death or suicidal ideation <\/em>in LLD are especially concerning. Older adults can act on their suicidal ideation with more serious intent, less warning, and more lethality than younger populations.29<\/sup> Signs that indicate impending suicide include feelings of hopelessness or lack of purpose, feeling trapped, talking about death, preparing for suicide, social withdrawal, increased substance use, and reckless behavior.6<\/sup> Factors believed to provide some protection against acting on suicidal thoughts include social connectedness, spirituality, religious beliefs, and cultural attitudes against suicide.6<\/sup><\/p>\n

    For older adults, particularly those living with physical illnesses, increasing somatic complaints <\/em>more so than typical symptoms of MDD are highly suggestive of LLD.30,31<\/sup> Persistent complaints of pain, headache, fatigue, insomnia, gastrointestinal distress; unexplained delayed recoveries after surgery; and failure to thrive in institutional settings can be linked to depression.31<\/sup> For people with cerebrovascular disease, any microdamage occurring in the small vessels compromises the ability of the frontal\u2010subcortical circuits to regulate mood, resulting in a depression known as vascular or subcortical ischemic depression.32,33<\/sup> Higher rates of LLD occur in people living with heart disease, diabetes, asthma, and arthritis.12<\/sup> While it is understandable that people will experience distress caused by their physical illnesses, it is important to emphasize that unexplained somatic complaints are indicative of LLD.<\/p>\n

    Finally, people experiencing loneliness<\/em>, or feeling as though they do not belong, are susceptible to LLD.34\u201336<\/sup> Studies indicate that between 5% and 10% of people between the ages of 60 and 80; and between 40% and 50% of people over 80 reported feeling lonely frequently.37<\/sup> Those at greatest risk of experiencing loneliness are women, particularly those who are older; and people who are without partners, are financially insecure and are physically unwell.37<\/sup> As many as 87% of older adults with depressive symptoms reported co\u2010occurring feelings of loneliness.36<\/sup> Loneliness has been found to exacerbate depressive symptoms, decrease quality of life, and leave older adults feeling as though they have no control over their situation.36<\/sup><\/p>\n

    In his seminal commentary on depression in later life, Dan Blazer urged clinicians not to limit their assessment of LLD to diagnostic categories of depression, but rather to include depressive symptoms that do not fully meet the criteria but nonetheless cause significant distress.20<\/sup> As the preceding discussion explained, older adults with symptoms of depression without sadness, lack of vigor, apathy and withdrawal, loss of interest, loss of appetite, early morning awakenings, decreased walking speed, physical tiring, frailty, memory loss or cognitive impairment with executive dysfunction, suicidal ideation, somatic complaints, and loneliness could be suffering from LDD. Recognizing and addressing these symptoms can decrease depression and functional impairment and enhance quality of life for older adults.38<\/sup> Next, actions that nurses can implement when they encounter the many older adults who are struggling with depression are suggested.<\/p>\n

    3    | PRACTICE IMPLICATIONS: ACTIONS THAT CAN HELP<\/h1>\n

    3.1     | Document symptoms of LLD<\/h2>\n

    Recognizing and documenting the aforementioned symptoms of LLD is a critical first step in helping people receive treatment for depression. Knowing that depressed older adults are more likely to present with loss of interest and unexplained somatic complaints than with a sad mood or self-identified complaints of depression, clinicians must intentionally inquire about LLD and maintain ongoing documentation. Seeking out information about any changes in lifestyle, social withdrawal, and feelings of loneliness from family members should also be included. Typical open ended interview questions that assess history, mental status, and level of cognitive and functional capacities should be followed by more directed questions specific to LLD.6<\/sup><\/p>\n

    3.2     | Screen with the Patient Health Questionaire\u20109<\/h2>\n

    Given the prevalence, impact and difficulties inherent in recognizing LLD, screening instruments can supplement interview findings and provide the objective data needed to indicate the risk or presence of depression in older adults.39<\/sup> The 9\u2010item Patient Health Questionnaire (PHQ\u20109), developed by Kroenke et al.40<\/sup> provides reliable, valid detection of depression in LLD.6,10,38,39<\/sup> The PHQ\u20109 is self\u2010administered, requires about 5 minutes to complete, is easily scored and interpreted, and is available for free.40<\/sup> The short questionnaire incorporates DSM\u20105 depression diagnostic criteria, as well as clinically significant depressive symptoms; rates the frequency of the symptoms and factors these into the scoring severity index; screens for suicidal ideation; and assigns weight to the depressive symptoms that impact how people function.40<\/sup> The PHQ\u20109 can be administered in a variety of settings both as an initial screening instrument and to follow up and evaluate interventions.10,38<\/sup><\/p>\n

    3.3     | Assess suicide risk<\/h2>\n

    As with any depressive illness, suicidal ideation means that protective factors must be assessed in people who may be experiencing LLD. Suicidal ideation can range from thinking passively about death and wishing to die, to active thoughts of self\u2010harm, plans, and an intention to die.6<\/sup> In older adults, means can include but are not limited to, hanging, firearms, poisoning, and hoarding medications.6<\/sup> Posing the question: \u201cWhat stops you?\u201d opens the door for people to express protective factors that are unique to their situation. Clearly, ongoing assessment, documentation, and immediate reporting of suicidal ideation must be implemented when LLD is or could be present.<\/p>\n

    3.4    | Pharmacological treatment<\/h2>\n

    Selective serotonin reuptake inhibitors (SSRIs) are the most common first\u2010line treatment for LLD.1,41<\/sup> The SSRI\u2010Sertraline (Zoloft), has a favorable side\u2010effect profile and can be taken by people with a history of cognitive impairment and stroke.41<\/sup> When SSRIs are contraindicated, alternative classes of antidepressants, such as Mirtazapine (Remeron), demonstrate good efficacy in older adults.41<\/sup> The side effects of Mirtazapine, which include sedation and weight gain, can have therapeutic benefit to the difficulty in sleeping and loss of appetite so commonly experienced in LLD. Tricyclic antidepressants, in particular, Nortriptyline (Allegron, Aventyl), can also be effective in older adults who do not have cardiac conditions or cognitive impairment.41<\/sup><\/p>\n

    Antidepressant medications are usually trialed for approximately 6 weeks; should not be withdrawn abruptly and can be expected to be taken for at least 2 years.41<\/sup> However, it is important to note that as many as one\u2010third of older adults will not respond to antidepressant treatment; relapse rates for those who do respond are high; and the approach is less efficacious than for younger people.13,42<\/sup><\/p>\n

    3.5     | Psychological treatment<\/h2>\n

    Psychological treatments, particularly when implemented in combination with pharmacological treatments have demonstrated moderate efficacy for some older adults.31,42,43<\/sup> Cognitive behavioral therapy (CBT), problem\u2010solving therapy (PST), interpersonal therapy (IPT), and reminiscence and life review therapy (RLRT) have been successfully implemented.43,44<\/sup> In CBT, people identify and challenge distorted thinking; in PST, people identify problems, brainstorm solutions, implement a solution, and then evaluate its effectiveness; in IPT, people explore feelings and ways to change behavior in relation to interpersonal relationships, including grief and role transitions; and in RLRT people review positive life events to enhance wellbeing.43<\/sup><\/p>\n

    Although therapies such as CBT, PST, and IPT are implemented by trained therapists, adaptions of RLRT and approaches to celebrating positive life events, both past and present, can readily be adapted in settings where nurses provide support to older adults. Similarly, behavioral activation (BA) therapy, which seeks to create a personal environment of positive reinforcement by increasing functional and pleasurable behavior, and by decreasing avoidant and depressed behavior, uses less complex protocols, and has successfully been implemented by mental health nurses.45<\/sup> Many older adults, especially those who are over 75 and are experiencing depression for the first time, prefer not to talk about their depression and do not view pharmacological and psychological treatments as likely to be helpful.11<\/sup> Therefore, exploring people\u2019s own ideas about the depression they are experiencing and the solutions they believe are valuable is foundational to any treatment approach.<\/p>\n

    3.6     | Electroconvulsive therapy<\/h2>\n

    Electroconvulsive therapy (ECT) can also be effective in treating LLD.7<\/sup> People who will benefit most from ECT are those with depression that is resistant to other treatments and for those at risk of serious harm because of psychotic depression, suicidal ideation, or severe malnutrition.46<\/sup> Although cardiovascular and cognitive side effects can occur with older adults, deleterious effects of ECT in LLD are usually limited and transient, with better cognitive outcomes with unilateral ECT.47<\/sup><\/p>\n

    In one study, when elderly people with unipolar depression were treated twice weekly with right unilateral ECT, their cognition, psychomotor agitation, and psychomotor retardation improved significantly.48<\/sup> This improvement was attributed to a significant gray matter volume increase, which was most pronounced on the side receiving neurostimulation.48<\/sup> Common side effects of ECT that nurses must monitor include headache that usually responds to analgesics, temporary confusion or memory impairment, and falls immediately after treatment sessions.46<\/sup><\/p>\n

    3.7     | Neuromodulation therapies<\/h2>\n

    Alternative neuromodulation therapies also provide neurostimulation, but unlike ECT, these therapies do not require anesthetic and have reduced side effects, making them safer for older adults with comorbid medical conditions.49<\/sup> Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct\u2010current stimulation (tDCS) modulate cerebral activity using brain stimulation and are usually implemented over a 4 to 6 week period.50<\/sup> In older adults with nonpsychotic depression, rTMS is well tolerated but higher intensities and greater numbers of treatments may be needed than for younger people.50<\/sup> Beyond its positive effects on mood, tDCS may also have positive effects on cognition.50<\/sup><\/p>\n

    3.8     | Physical exercise<\/h2>\n

    Physical exercise programs can improve outcomes with some symptoms of LLD. In combination with antidepressant medication, exercise programs for older adults that included brief intervals of increased workload were found to decrease symptoms of depressed mood and psychomotor retardation.51<\/sup> Aerobic activities, which stimulate and sustain heart and breathing rates, improved cognition and reduced disability in depressed older adults.52<\/sup><\/p>\n

    When high intensity progressive resistance training was integrated into exercise programs, participants\u2019 sleep quality improved.53<\/sup> Knowing that sleep disturbances are frequently
    \npresent in LLD,3,23<\/sup> the value of integrating resistance training into older adults\u2019 physical activities becomes clear. Weekly group exercise programs of 3 \u00d7 50 minute sessions, which included
    \nmoderate cardiovascular exercise, such as walking with waving or clapping hands to music for a duration of 30 minutes, improved quality of life and perceived social support.54<\/sup> Exergames or
    \nentertaining video games that combined game play with exercise decreased subsyndromal symptoms of depression55,56<\/sup> and improved balance and mobility.55<\/sup><\/p>\n

    In community settings, nurses can encourage older adults to participate in seniors\u2019 fitness activities in their area. In institutional settings, they can advocate for the creation of fitness programs that personalize physical exercise for patients\/residents. Although medical conditions can impose limitations on peoples\u2019 mobility, engaging in some form of daily physical exercise can make an important difference in mood.<\/p>\n

     <\/p>\n

    3.9     | Lifestyle modifications<\/h2>\n

    In addition to increasing physical exercise, lifestyle modifications, such as improving dietary patterns and addressing vitamin D deficiencies may also exert a positive influence on some symptoms of depression. Emerging evidence suggests that modifying dietary patterns may reduce the risk of developing depression.57<\/sup> Actions that can help include: following the Mediterranean diet; increasing consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; including a high consumption of foods rich in omega\u20103 polyunsaturated fatty acids; replacing unhealthy foods with wholesome nutritious foods; and limiting intake of processed foods, \u201cfast\u201d foods, commercial bakery goods, and sweets.57<\/sup><\/p>\n

    Although causal links between vitamin D deficiency and the development of depression have not been established, studies reveal that vitamin D deficiency accompanies late\u2010life depression.58<\/sup> For older adults, the skin capacity to synthesize vitamin D from sunlight can be reduced as much as 25%, increasing the likelihood of vitamin D deficiency.58<\/sup> Those who have limited opportunities to be outdoors or to be exposed to sunlight are particularly at risk. The 25\u2010hydroxy vitamin D blood test indicates that vitamin D deficiency exists when levels are less than 12.5 ng\/mL.59<\/sup> Vitamin D supplements may be helpful.<\/p>\n

    4 | CONCLUSION<\/h1>\n

    Adults over 60 can experience symptoms of depression somewhat differently than younger people. Older adults living with LLD may not appear sad or express feelings of depression. Instead, they may demonstrate loss of interest, frailty, cognitive impairment, suicidal ideation, unexplained somatic complaints, and loneliness. In response, nurses should document these symptoms, screen with the PAQ\u20109 and, importantly, assess for suicidal ideation. Antidepressant medications, CBT, electroconvulsive therapy, neuromodulation therapies, physical exercise, and lifestyle modifications can bring needed support and relief to the increasing number of people burdened with LLD.<\/p>\n

    CONFLICTS OF INTEREST<\/h1>\n

    The authors declare that there are no conflicts of interest.<\/p>\n

    ORCID<\/h1>\n

    Sherri Melrose       <\/em>http:\/\/orcid.org\/0000-0002-2056-8547<\/a><\/p>\n

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      \n
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