Exploratory pilot study exploring clinical effects of exogenous sustained-release Melatonin on nocturia in Parkinson’s Disease

Introduction: Nocturia is one of the commonest non‐motor symptoms in Parkinson’s disease (PD). Nocturia has evolved from being understood as a symptom of urological disorders or neurogenic bladder dysfunction to being considered as a form of circadian dysregulation. Exogenous melatonin is known to help circadian function and can be an effective strategy for nocturia in PD. Methods: In this open label single‐site exploratory phase 2 pilot study, adults with PD and nocturia underwent assessments using standardised questionnaires, urodynamics studies and a bladder scan. This was followed by completion of a frequency volume charts (FVC) and two weeks sleep diary. Sustained‐release melatonin 2mg was then administered once nightly for six weeks. A repeat assessment using questionnaires, the FVC and sleep diary was performed whilst on treatment with melatonin. Companion or bed partners filled in sleep questionnaires to assess their sleep during the intervention. Results: 20 patients (12 males; mean 68.2 (SD=7.8) years; mean PD duration 8.0 (±5.5) years with PD reporting nocturia were included. Administration of melatonin was associated with a significant reduction in the primary outcome bother related to nocturia measured using the International Consultation on Incontinence Questionnaire Nocturia (ICIQ‐N) (p=0.01), number of episodes of nocturia per night (p=0.013) and average urine volume voided at night (p=0.013). No serious adverse events were reported. No significant improvement was noted in bed‐partner sleep scores. Conclusion: In this preliminary open‐label study, administration of sustained‐release melatonin 2mg was found to be safe for clinical use and was associated with significant improvements in night‐time frequency and nocturnal voided volumes in PD patients

Conservative management for urinary incontinence in neurological patients: A systematic review and meta-analysis

Aim: To summarize evidence from a search and review of the 7th International Consultation on Incontinence chapter’s section on conservative treatments in neurological patients. Methods: Searching the Cochrane Incontinence Specialised Register (MEDLINE, CENTRAL, others) on August 2nd, 2022. Quality and certainty evidence were assessed using the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development and Evaluation. Results: After screening 5416 records, 40 trials with 2751 participants were included and stratified according to the site and nature of the neurological disease: (1) Brain disorders n = 22; (2) Spinal cord disorders n = 3; (3) Multiple sclerosis (MS) n = 13; (4) Mixed types of neurological diseases n = 2. Pooled analysis from trials in participants with brain disorders showed that, compared to no active treatment, electrical stimulation (EStim) improved UI episodes per day based on very low certainty evidence and improved UI symptom measures based on moderate certainty evidence. Further, compared to usual care, toilet assistance improved neurological quality of life (QoL) measures based on moderate certainty evidence. Pooled analysis from trials in participants with MS showed that, compared to pelvic floor muscle training (PFMT) alone, PFMT plus EStim was effective for improving the number of UI episodes per day based on moderate certainty evidence. Conclusion: Our review shows that neurological patients could benefit from conservative interventions to improve symptoms of UI, and QoL. Further well-designed trials with larger cohorts and longer-term follow-up are needed given the limited studies in this population

The Management of Lower Urinary Tract Dysfunction in Multiple Sclerosis

Purpose of Review Multiple sclerosis (MS) is the most frequent neuroinflammatory disease of the central nervous system and is commonly associated with lower urinary tract (LUT) dysfunction. As a consequence, health-related quality of life is often impaired and the upper urinary tract might be at risk for damage. The aim of this review is to give an overview of current treatment options for LUT dysfunction in patients with MS. Recent Findings The treatment is tailored to the type of dysfunction—storage or voiding dysfunction—beginning with conservative treatment options and ending with invasive therapies and surgery. Additionally, alternative options, e.g., different intravesical therapies or cannabinoids, have been evaluated in recent years with promising results. Summary Current available therapies offer different possible treatments for LUT dysfunction in patients with MS. They address either voiding or storage dysfunction and therefore ameliorate LUT symptoms improve quality of life and protect the upper urinary tract

Gut dysfunction in patients with multiple sclerosis and the role of spinal cord involvement in the disease.

Bowel and bladder symptoms are highly prevalent in patients with multiple sclerosis (MS). Bladder dysfunction (affecting 75% of these patients) is caused by disease in the spinal cord, whilst the pathophysiology of bowel dysfunction is unknown. Pathways regulating both the organs lie in close proximity to the spinal cord, and coexistence of their dysfunction might be the result of a common pathophysiology. If so, the prevalence of bladder symptoms should be greater in patients with MS and bowel symptoms. This hypothesis is tested in the study. We also evaluated how patient-reported symptoms quantify bowel dysfunction

COVID-19 and fear processing

The world faces a global crisis that encompasses health, financial, and psychological aspects as a result of the coronavirus disease. While the health crisis is significant, it is important to recognize that the human and social crises that have emerged are equally impactful. These crises have resulted in various negative outcomes, such as social rejection, economic disparity, unemployment, and mental distress. Fear is a significant psychological barrier that can impede recovery from any disease process, and thus, it plays a critical role in determining the mortality and morbidity of any given disease. The COVID-19 pandemic has generated a pervasive fear of infection that has further exacerbated the situation. This study explored the mechanisms by which humans may have elicited conditional fear, using the COVID-19 pandemic as a specific case study. Our goal was to examine the process of fear in humans by exploring our knowledge of neuroanatomy and the systemic response regulated by the autonomic nervous system

Urinary tract infections in multiple sclerosis

BACKGROUND: Urinary tract infections (UTIs) are commonly reported by people with multiple sclerosis (PwMS) and significantly impact quality of life. OBJECTIVE: To provide an overview of the problem of UTIs in PwMS and offer a practical approach for the diagnosis and management. METHODS: A review of the literature through a Pubmed search up to October 2015 was performed using the following keywords: multiple sclerosis, neurogenic bladder, urinary tract infections, relapse, dipsticks, culture, recurrent and prevention. RESULTS: Noteworthy topics include the definition of a confirmed symptomatic UTI as a positive urine culture defined by >10(5) colony-forming units (CFU)/mL or >10(4) CFU/mL if a urethral catheter urine sample is taken, or any count of bacteria in a suprapubic bladder puncture specimen, both in addition to symptoms including fever, pain, changes in lower urinary tract symptoms or neurological status. Urinalysis is useful to exclude a UTI; however, on its own is insufficient to confirm a UTI, for which urine culture is required. Experts advise asymptomatic UTIs should not be treated except in the context of an acute relapse. From international guidelines, there is no validated strategy to prevent recurrent UTIs in PwMS. CONCLUSION: This review provides an overview of the diagnosis, treatment and prevention of UTIs in the setting of multiple sclerosis (MS)

The prevention and management of hospital admissions for urinary tract infection in patients with multiple sclerosis

Introduction Urinary tract infections (UTIs) are one of the commonest reasons for patients with multiple sclerosis (PwMS) presenting to hospital. Management of recurrent UTIs in PwMS can be challenging and characteristics of such patients are not well described. Aims To describe the neurological and urological features of PwMS presenting to hospital for UTIs and identify areas of management that could be improved to reduce UTI frequency. Methods Health episode statistics data were used to identify PwMS presenting to a tertiary hospital with UTI over a 5-year period. Medical records were reviewed for demographic, MS and urological history. The seven PwMS with the highest numbers of encounters were seen in a multidisciplinary clinic to enable detailed assessments. Results 52 PwMS (25 female, 27 male) with mean age of 60 had 112 emergency department presentations and 102 inpatient admissions for UTI. 24 presented multiple times and were more likely to be older and male with progressive MS. Almost two-thirds were using a urinary catheter. Less than half were under current urological and neurological follow-up. Escherichia coli and Pseudomonas spp were the commonest organisms cultured. Resistance to antibiotics was more frequent in patients with multiple presentations. Conclusions PwMS presenting to hospital for UTIs are more often male, older, with progressive MS and high levels of disability. A small group of PwMS accounted for a large number of encounters. Preventative and management strategies can be applied in primary and secondary care settings, with an emphasis on bladder, catheter and general physical care

Offspring conceived through ART have normal thyroid function in adolescence and as young adults

STUDY QUESTION: Are there differences in thyroid function between adolescents and young adults conceived with and without ART? SUMMARY ANSWER: This study demonstrated no evidence of clinically relevant differences in thyroid function between adolescents and young adults conceived with and without ART. WHAT IS KNOWN ALREADY: Studies to date have reported an increase in subclinical hypothyroidism in offspring conceived after ART. It has been suggested that the increase in maternal estrogen (E2) after fresh embryo transfers could affect thyroid function of the offspring. Suboptimal thyroid function at a young age can cause irreversible damage to the central nervous system, which makes early detection and correct treatment essential. STUDY DESIGN, SIZE, DURATION: The Growing Up Healthy Study (GUHS) is a prospective cohort study, which aimed to recruit all adolescents born after conception with ART between 1991 and 2001 in the study area. The included participants (n = 303, aged 13-20 years) completed various health assessments. Depending on the age at enrolment, participants completed thyroid assessments at the 14-or 20-year follow-up. The outcomes of these replicated thyroid assessments were compared to those of participants conceived without ART from the Raine Study Generation 2 (Gen2). The Gen2 participants (n = 2868) were born between 1989 and 1992 and have been recognized to be representative of the local population. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thyroid function assessments were compared between n = 134 GUHS and n = 1359 Gen2 adolescents at age 14 years and between n = 47 GUHS and n = 914 Gen2 young adults at age 20 years. The following mean thyroid hormone concentrations were compared between the cohorts: Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and thyroid peroxidase antibodies (TPOAb). The prevalence of the following thyroid hormone profiles, based on individual thyroid hormone concentrations, was compared: euthyroidism, subclinical and overt hypo-and hyperthyroidism and thyroid autoimmunity. Outcomes were compared between the cohorts, and univariately between fresh embryo transfers (ET) and frozen ET (FET) within the GUHS. The correlation between maternal peak E2 concentrations (pE2) and fT4 was assessed within the GUHS. MAIN RESULTS AND THE ROLE OF CHANCE: All mean thyroid function outcomes fell within the normal range. At both ages, we report no differences in TSH concentrations. At age 14 years, lower fT3 concentrations (4.80 versus 5.35 pmol/L, P \u3c 0.001) and higher fT4 concentrations (12.76 versus 12.19 pmol/L, P \u3c 0.001) were detected in the GUHS adolescents compared to Gen2 adolescents. At age 20 years, higher fT3 and fT4 concentrations were reported in GUHS adolescents (4.91 versus 4.63 pmol/L, P = 0.012; 13.43 versus 12.45 pmol/L, P \u3c 0.001, respectively) compared to Gen2 participants. No differences in the prevalence of subclinical and overt hypo-and hyperthyroidism or thyroid autoimmunity were demonstrated between the cohorts at age 14 and 20 years. Thyroid function did not differ between ET and FET, and no correlation between pE2 and fT4 was reported. LIMITATIONS, REASONS FOR CAUTION: The observational nature of the study limits the ability to prove causation. Furthermore, the comparison of ET and FET offspring at age 20 years may be lacking power. We were unable to differentiate between different types of ART (e.g. IVF versus ICSI) owing to the low number of ICSI cycles at the time of study. As ART laboratory and clinic data were collected contemporaneously with the time of treatment, no other data pertaining to the ART cycles were sought retrospectively; hence, some factors could not be accounted for. WIDER IMPLICATIONS OF THE FINDINGS: This study does not support previous findings of clinically relevant differences in thyroid function when comparing a cohort of adolescents conceived after ART to counterparts conceived without ART. The minor differences detected in fT3 and fT4 were considered not biologically relevant. Although these findings appear reassuring, they warrant reinvestigation in adulthood. STUDY FUNDING/COMPETING INTERESTS: This project was funded by an NHMRC Grant (Hart et al., ID 1042269). R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director and a shareholder of PIVET Medical Centre, Perth, Western Australia. TRIAL REGISTRATION NUMBER: N/A