Delayed and significant hypercalcaemia due to teriparatide therapy: a case report and review.

INTRODUCTION: Transient hypercalcaemia due to teriparatide occurs in up to 11% of patients though delayed hypercalcaemia (> 24 h post injection) is rare. We report the case of a female who developed significant delayed hypercalcaemia after teriparatide treatment for osteoporosis and review other cases in the literature to date. CASE REPORT: A 72-year-old female on teriparatide for the treatment of osteoporosis was found to have hypercalcaemia (3.30 mmol/l) on routine testing approximately 3 months after starting therapy. Serum calcium pretreatment was normal at 2.39 mmol/l. She was admitted to the hospital for investigations which identified a serum 25-hydroxyvitamin D of 94 nmol/l, a low parathyroid hormone of 6.0 pg/ml, and normal test results for 1,25 dihydroxyvitamin D (115 pmol/l), parathyroid hormone-related peptide (< 1.4 pmol/ml), serum electrophoresis and angiotensin-converting enzyme (39 IU/l). CT abdomen, pelvis, and thorax revealed no evidence of malignancy and an isotope bone scan ruled out skeletal metastases. Serum calcium normalised (2.34 mmol/l) several days after stopping teriparatide and calcium supplements and administering intravenous fluid. On restarting teriparatide, delayed hypercalcaemia reoccurred and treatment was switched to denosumab. DISCUSSION: Delayed moderate to severe hypercalcaemia (serum calcium > 3.0 mmol/l) due to teriparatide is rare but may lead to therapy withdrawal. The underlying predisposing risk factors remain unclear and highlight the importance of a routine serum calcium assessment on therapy.

Treatment Challenges When Stopping Denosumab.

Introduction Denosumab is commonly used to treat osteoporosis. However, discontinuation results in rebound bone loss and increased vertebral fracture risk. We report a clinical case series, illustrating the dilemma in deciding the best treatment should denosumab be stopped. Cases In eight patients aged 56-89 years, zolendronic acid after stopping denosumab resulted in BTM rises and BMD decline.  In a 68-year-old, two years of oral bisphosphonate after three years of denosumab resulted in elevated bone turnover markers (BTM) and decline in bone mineral density (BMD), necessitating a switch to zoledronic acid.  In a 79-year-old, two annual doses of zolendronic acid after three years of denosumab failed to suppress high BTM, with BMD dropping and denosumab being restarted.  In a 60-year-old, on stopping denosumab after 10 years of oral bisphosphonate, BMD remained stable despite no further therapy. Conclusion Drug holidays are not an option with denosumab, with a risk of bone loss even on transitioning to bisphosphonates. Risk is greater with longer duration of treatment6 and may be mitigated by prior bisphosphonate use. Standard dose zoledronic acid does not prevent bone loss in a significant proportion of patients. BTM may help in monitoring treatment and need for further bisphosphonates.

Fracture liaison services in Ireland-how do we compare to international standards?

In this first na tional survey of public hospitals in The Republic of Ireland, we found fracture liaison services (FLS) to be heterogeneous, limited in many cases and poorly supported. A national strategy is urgently needed to support the implementation and operation of an FLS, and thus help reduce the burden of fragility fractures for patients and the healthcare system. INTRODUCTION: Fragility/low-trauma fractures are a global concern, whose incidence is rising as the population ages. Many are preventable, and people with a prior fragility fracture are at particularly high risk of further fractures. This patient group is the target of the International Osteoporosis Foundation (IOF) Capture the Fracture campaign, advocating global adoption of fracture liaison services (FLS), with the aim of preventing secondary fragility fractures. We wished to determine the current availability and standards of an FLS in Ireland, ahead of the launch of a National FLS database. METHODS: We devised a questionnaire encompassing the thirteen IOF standards for an FLS and asked all 16 public hospitals with an orthopaedic trauma unit in Ireland, to complete for the calendar year 2019 in patients aged ≥ 50 years. RESULTS: All sites returned the questionnaire, i.e. 100% response rate. Nine hospitals stated that they have an FLS, additionally one non-trauma hospital running a FLS responded, and were included. These 10 FLS had identified and managed 3444 non-hip fractures in the year 2019. This figure represents 19% of the expected non-hip fragility fracture numbers occurring annually in Ireland. Implementation of the IOF standards was very variable. All sites reported being inadequately resourced to provide a high-quality service necessary to be effective. CONCLUSION: The existence and functioning of FLS in Ireland are heterogeneous and suboptimal. A national policy to support the implementation of this programme in line with international standards of patient care is urgently needed.

Physical and mental health of older people while cocooning during the COVID-19 pandemic.

BACKGROUND: Cocooning or shielding, i.e. staying at home and reducing face-to-face interaction with other people, was an important part of the response to the COVID-19 pandemic for older people. However, concerns exist regarding the long-term adverse effects cocooning may have on their physical and mental health. AIM: To examine health trajectories and healthcare utilization while cocooning in a cohort of community-dwelling people aged ≥70 years. DESIGN: Survey of 150 patients (55% female, mean age 80 years and mean Clinical Frailty Scale Score 4.8) attending ambulatory medical services in a large urban university hospital. METHODS: The survey covered four broad themes: access to healthcare services, mental health, physical health and attitudes to COVID-19 restrictions. Survey data were presented descriptively. RESULTS: Almost 40% (59/150) reported that their mental health was 'worse' or 'much worse' while cocooning, while over 40% (63/150) reported a decline in their physical health. Almost 70% (104/150) reported exercising less frequently or not exercising at all. Over 57% (86/150) of participants reported loneliness with 1 in 8 (19/150) reporting that they were lonely 'very often'. Half of participants (75/150) reported a decline in their quality of life. Over 60% (91/150) agreed with government advice for those ≥70 years but over 40% (61/150) reported that they disliked the term 'cocooning'. CONCLUSIONS: Given the likelihood of further restrictions in coming months, clear policies and advice for older people around strategies to maintain social engagement, manage loneliness and continue physical activity and access timely medical care and rehabilitation services should be a priority.

Geriatric medicine in the emergency department.

Studies suggest older adults attending emergency departments(ED) benefit from specialist geriatric medicine evaluation. Findings from a pilot ED Geriatric Medicine(GM) liaison service in our 480-bed university hospital are presented. This is not a randomized controlled trial. Service comprised consultant geriatrician and senior trainee-led sessions during daytime working hours. Senior ED personnel selected appropriate patients. GM service also took over ED medical admissions aged 80, 1 in 9 days from General Internal Medicine(GIM). 49% of 284 patients (83.5 +/- 6.8 years) referred, were discharged from ED with appropriate follow-up. Inpatient analysis comprised 51% admitted to GIM, GM and specialist services as per on-call rota and 268 patients taken over from GIM. Patients under GM had shorter length of stay (p < 0.001). The findings suggest specialty specific geriatric medicine management of the older adult presenting to ED can improve service and patient outcomes.

An audit of the impact of a stroke unit in an acute teaching hospital.

BACKGROUND: Previous audits of stroke care in 2002 and 2005 in our institution recommended organised and specialised care of stroke patients. A stroke unit was therefore established in June 2008. AIM: This audit assessed the impact of the establishment of an acute stroke unit on the care of stroke patients. METHOD: A review of consecutive patients admitted and diagnosed with acute stroke between June 2008 and December 2008 was carried out. Comparison was made with 55 consecutive patients surveyed in 2005. RESULTS: Marked improvements in the management of acute stroke patients were noted, particularly time to computerised tomography of brain, aspirin administration and multidisciplinary involvement. Significantly, the average length of hospital stay was reduced by a mean of 10 days from 29.3 ± 28 in 2005 to 19.6 ± 20 following the establishment of a stroke unit (p = 0.018). CONCLUSIONS: The stroke unit has greatly improved the care of acute stroke patients. Further areas for improvement are highlighted.

Affect, attachment, memory: contributions toward psychobiologic integration.

Recent decades have seen a marked expansion in knowledge regarding human neurophysiology, and psychiatry is currently challenged with the task of integrating this information with a psychodynamic understanding of emotional life. In this paper we review portions of the relevant literature regarding the basic brain functions of affect, memory, and attachment, and we consider the implications of these data for integrated psychobiologic conceptualizations of emotional dysfunction and its treatment. In particular, data from these three areas of study point to the possibility that implicit memory of the early attachment relationship, communicated via the language of affect, is an enduring neural structure that influences both emotional self-regulation and behavior related to relatedness. Finally, we consider the implications of this proposition for the nature of psychotherapy, which from a psychobiologic view might be profitably conceptualized as a directed attachment relationship whose purpose is the revision of the implicit emotional memory of attachment.

Use of low-dose fluoxetine in major depression and panic disorder.

BACKGROUND: Recent reports suggest that fluoxetine in doses less than the standard 20 mg/day may be effective in the treatment of depression and that some patients, particularly those with panic disorder, may be intolerant of the 20 mg/day dose. We examined the utility of starting fluoxetine at a low daily dose (5 mg) and increasing to the standard daily dose (20 mg) in depressed outpatients with and without concurrent panic disorder. METHOD: One hundred thirty-three consecutive outpatients meeting DSM-III-R criteria for major depression were studied. Patients were started on fluoxetine 5 mg/day and were gradually increased to 20 mg/day over a 1-week period. Patients who were unable to reach the 20 mg/day dose were instructed to take the highest tolerable dose for the duration of the study. After a month of fluoxetine treatment, patients were evaluated for compliance with treatment and improvement on the Clinical Global Improvement scale. RESULTS: Twenty-eight percent of the patients were unable to increase the dose to the full 20 mg. Of these patients, half could not tolerate doses lower than 20 mg and discontinued the drug, while the other half did well clinically on the lower doses. Patients who discontinued fluoxetine tended to have panic disorder in addition to depression. CONCLUSION: We conclude that starting fluoxetine at doses lower than 20 mg is a useful strategy because of the substantial fraction of patients who cannot tolerate a 20-mg dose but appear to benefit from lower doses. This dosing strategy may be of particular benefit for patients with panic disorder.

Association of maternal lithium exposure and premature delivery.

Lithium is widely used and the treatment of choice for patients with manic-depressive illness. For pregnant patients with manic-depressive illness, however, the use of lithium during the first trimester of pregnancy may present an increased risk for fetal maldevelopment. We have recently cared for several large-for-gestational-age, prematurely born infants whose mothers were treated with lithium throughout pregnancy. To determine whether maternal lithium use during pregnancy may predispose to the onset of premature labor and fetal macrosomia, we reviewed records from the International Register of Lithium Babies and from a cohort of manic-depressive pregnant women. More than one third (36%) of infants reported to the International Register were born prematurely, and 37% of the premature infants were large for gestational age; 15% of the term infants were born large for gestational age. In the cohort group, manic-depressive mothers who received lithium during pregnancy had a 2.5-fold higher incidence of premature births than manic-depressive pregnant patients who did not receive lithium treatment. The incidence of large-for-gestational-age births in lithium-treated women in the cohort was not different from that of the general population or from manic-depressive women not treated with lithium. In summary, an association between maternal lithium therapy and premature delivery is reported. We recommend that women receiving lithium therapy during pregnancy be closely monitored for the onset of premature labor.

Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder.

In a sample of 114 patients, 6 patients developed hypertension while taking tricyclic antidepressants. All these patients were diagnosed as having panic disorder, with or without major depression. Half of the 6 patients had a previous diagnosis of hypertension, which had been well controlled by antihypertensive drugs for years. A comparison group of patients with major depression, who had never had panic attacks, had no cases of hypertension induced by these antidepressants. These findings raise the possibility that patients who have panic disorder may experience cardiovascular disregulation that increases their risk for antidepressant-induced hypertension.

The effects of clonidine and yohimbine on human information processing.

The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18-30 years. Subjects were tested in a pre-post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive to d-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre-processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings with d-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage.

Treatment of cocaine-induced panic disorder.

The authors describe 10 patients who developed panic attacks only after substantial cocaine use. The timing of the onset of symptoms, i.e., after 1-6 years of cocaine use, and the fact that only one patient had a first-degree relative with panic disorder were more suggestive of acquired than primary panic disorder. The patients' atypical symptoms and responses to medications may be explained in terms of limbic-neuronal hyperexcitability induced by cocaine through a kindling mechanism.