Category: Nevin Manimala

CNS Drugs. 2022 Nov 27. doi: 10.1007/s40263-022-00974-6. Online ahead of print.

ABSTRACT

The orexin (hypocretin) system comprises two neuropeptides (orexin-A and orexin-B) and two G-protein coupled receptors (the orexin type 1 and the orexin type 2 receptor). The system regulates several biological functions including appetite, the sleep-wake cycle, the stress response, and motivation and reward processing. Dysfunction of the orexin system has been implicated in the pathophysiology of depression in human and animal studies, although the exact nature of this dysfunction remains unclear. Orexin receptor antagonists (ORAs) are a class of compounds developed for the treatment of insomnia and have demonstrated efficacy in this area. Three dual orexin receptor antagonists (DORAs) have received licences for treatment of primary insomnia and some ORAs have since been investigated as potential treatments for major depressive disorder (MDD). In this leading article, we summarise the existing literature on use of ORAs in depression, in pre-clinical and clinical studies. In rodent models of depression, investigated ORAs have included the DORA almorexant and TCS1102, the selective orexin 1 receptor antagonists SB334867 and SB674042 and the selective orexin 2 receptor antagonists LSN2424100, MK-1064 and TCS-OX2-29. These pre-clinical studies suggest a possible antidepressant effect of systemic DORA treatment, however the evidence from selective ORAs is conflicting. To date, four published RCTs (one with the DORA filorexant and three with the selective orexin 2 receptor antagonist seltorexant), have compared an ORA with placebo in the treatment of MDD. Only one of these demonstrated a statistically significant difference relative to placebo.

PMID:36436175 | DOI:10.1007/s40263-022-00974-6

Drugs Real World Outcomes. 2022 Nov 27. doi: 10.1007/s40801-022-00342-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Deprescribing is associated with positive health outcomes for older adults in long-term care (LTC), however deprescribing is not universally implemented.

OBJECTIVE: The primary aim of this study was to estimate the prevalence of potentially inappropriate medications (PIMs) prescribed to frail older adults in Irish long-term care facilities (LTCFs), as identified by the Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy, version 2 (STOPPFrail v2).

METHODS: A retrospective chart review was conducted in two publicly funded LTCFs in Ireland. Eligible participants were those (1) ≥ 65 years of age; (2) resident in a LTCF; (3) eligible as per the STOPPFrail v2 criteria by the site’s Medical Officer; and (4) receiving regular medication. Data collected included age, sex, drug, dose, frequency, regular/pro re nata prescribing and indication/relevant diagnoses. Rates of polypharmacy (taking five or more medications) and excessive polypharmacy (taking 10 or more medications) were calculated. STOPPFrail v2 was used to identify PIMs; however, clinical measurements were not taken. Descriptive and association statistics were calculated.

RESULTS: Of the 103 residents, 89 were ≥ 65 years of age and categorised as frail and were therefore eligible for inclusion in the study. Of those eligible, 85 (95.5%) had polypharmacy and 57 (64%) experienced excessive polypharmacy. The mean number of regular medications was 10.8 (± 3.8), total medications 17.7 (± 5) and diagnoses 5.5 (± 2.5). The mean number of PIMs per resident was 4.8 (± 2.6). Of the eligible participants, 59.6% had at least one medicine without a documented indication, while 61.8%, 42.7% and 30.3% had at least one PIM from the vitamin D, antihypertensives and proton pump inhibitors drug classes, respectively.

CONCLUSION: Medication and PIM use was high among LTC residents, with inappropriate polypharmacy of concern. Lack of clear indication for prescribing medications appears to be an issue in LTC, potentially affecting healthcare professionals’ engagement with deprescribing. The prevalence of PIMs may be overestimated in the antihypertensives/antidiabetic classes due to the lack of clinical measurements.

PMID:36436174 | DOI:10.1007/s40801-022-00342-2

Int Ophthalmol. 2022 Nov 27. doi: 10.1007/s10792-022-02584-z. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the risk factors of DM associated dry eye syndrome (DMDES) and to explore the effect of diquafosol sodium ophthalmic solution (DQS) on patients with DMDES after vitrectomy.

METHODS: Totally 107 patients (107 eyes) received vitrectomy. The data of age, gender, left/right eye, duration of DM, duration of vitrectomy, fasting blood glucose and glycosylated hemoglobin were collected and analyzed for correlation between these factors and DMDES. Postoperatively, DQS was instilled in experimental group and sodium hyaluronate was instilled in control group. The noninvasive breakup time (NIBUT), tear meniscus height (TMH), Schirmer I test (SIT), corneal fluorescence staining score (CFSS) and ocular surface disease index (OSDI) were recorded before vitrectomy and 1, 2 and 3 months after vitrectomy. All data were used for statistical comparison.

RESULTS: Gender, duration of DM and glycosylated hemoglobin were relevant factors of DMDES (P < 0.05). At 1, 2 and 3 months postoperatively, NIBUT and TMH of experimental group were significantly higher than control group (P < 0.05). Postoperatively, CFSS of experimental group was lower than that before vitrectomy, and CFSS at 2 and 3 months after vitrectomy was significantly different between the two groups (P < 0.05). At 1, 2 and 3 months postoperatively, SIT increased in both groups, but there was no significant difference between the two groups (P > 0.05). OSDI was significantly lower in experimental group at 1, 2 and 3 months postoperatively, compared with that of the control group (P < 0.05).

CONCLUSION: These results suggest that gender, duration of DM and glycosylated hemoglobin are risk factors for DMDES. Postoperative instillation of DQS can improve the tear film quality in patients with DMDES after vitrectomy.

PMID:36436170 | DOI:10.1007/s10792-022-02584-z

Int Ophthalmol. 2022 Nov 27. doi: 10.1007/s10792-022-02598-7. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the clinical features, treatment, and visual outcome of patients with acute retinal necrosis (ARN).

METHODS: The data of patients were retrospectively reviewed. Factors associated with visual loss and factors affecting the risk for retinal detachment (RD) development were evaluated.

RESULTS: Twenty-four eyes of 24 patients (7 female/17 male, mean age 43.7 years, mean follow-up period 31.0 months) were included. In ocular fluid samples of 15 (83%) out of 18 eyes, polymerase chain reaction (PCR) tests were positive for herpes simplex virus (seven eyes; 39%), varicella zoster virus (six eyes; 33%), cytomegalovirus (one eye; 6%), and adenovirus (one eye; 6%). Central retinal occlusive vasculitis was observed in three (13%) eyes. Systemic antiviral therapy was given to all patients, and additional intravitreal ganciclovir was administered in seven eyes (29%). The most common complication was RD (46%). There was no statistically significant difference in the frequency of RD between herpes simplex virus- and varicella zoster virus-positive patients (p = .617). The rate of RD was similar in eyes undergoing prophylactic laser photocoagulation (LPC), eyes undergoing vitrectomy + LPC, and eyes not undergoing LPC (p = .237). The number of eyes with final visual acuity below 20/200 was significantly higher in eyes with RD than without RD (p = .047).

CONCLUSION: Prophylactic LPC and vitrectomy did not show clear benefits in terms of preventing RD development. RD was the most common complication and a major factor for a poor visual prognosis.

PMID:36436167 | DOI:10.1007/s10792-022-02598-7

J Community Health. 2022 Nov 27. doi: 10.1007/s10900-022-01172-7. Online ahead of print.

ABSTRACT

This paper analyses community knowledge, perceptions, and experiences of effectiveness of healthcare service provision on malaria prevention/treatment in two disease-endemic villages of the Okavango Delta panhandle in northern Botswana. A stratified random sampling of 355 households was conducted in October-November 2015. Follow-up retrospective cohort interviews were undertaken in August 2016 from 79 households that reported malaria incidences during the household survey. Data were also collected from 16 key informant interviews and 2 focus group discussions participants. Descriptive statistics and content analyses were used to summarise quantitative and qualitative data, respectively. Results indicate that communities in the study sites had positive perceptions about efficiency of health services based on availability, accessibility and utilization, adequacy of prevention and treatment interventions. Local health clinics were crucial information channels used by respondents. Additionally, factors related to acceptability, availability and accessibility are likely to contribute to perceived effectiveness of the interventions provided by healthcare service providers. Affirmation of efficiency health service provision against malaria has public health implications for adherence to treatment/prevention and participation in community health education campaigns and program implementation in the Okavango Delta region.

PMID:36436166 | DOI:10.1007/s10900-022-01172-7

Updates Surg. 2022 Nov 27. doi: 10.1007/s13304-022-01428-w. Online ahead of print.

ABSTRACT

Central lymph-node dissection (CND) as part of total thyroidectomy is recommended in the treatment of papillary thyroid cancer. CND with thymus resection for achieving more oncological clearance is suggested in guidelines, but the benefits of this technique are still unclear due to the risk of parathyroid glands injury and postoperative hypocalcemia. The aim of this study is to evaluate the risk and benefits of thymectomy in CND with total thyroidectomy. We retrospectively reviewed the records of 188 patients with total thyroidectomy and CND. Participants were divided into 110 patients with CND and thymus resection and 78 patients with thymus preservation. Oncological completeness was evaluated by measuring the postoperative thyroglobulin and hypocalcemia as a postoperative complication was measured by blood calcium level. Based on our findings, patients who underwent thymus resection had a higher incidence of hypocalcemia compared to patients with thymus preservation (56.4% vs. 39.2%; P = 0.027), but there was no significant difference in thyroglobulin levels between these two groups. (P = 0.115 and 0.185, respectively) The proportion of involved to total resected lymph nodes in our study was 28%, which did not statistically differ among the thymus groups. Routine thymus resection during the CND and total thyroidectomy is not recommended because of more postoperative hypocalcemia occurrence and minimal oncological benefit in PTC treatment.

PMID:36436160 | DOI:10.1007/s13304-022-01428-w

Ann Nucl Med. 2022 Nov 27. doi: 10.1007/s12149-022-01810-z. Online ahead of print.

ABSTRACT

OBJECTIVE: Transarterial radioembolization (TARE) with Yttrium-90 (⁹⁰Y) labeled microspheres is an effective locoregional treatment option for patients with primary and metastatic liver cancer. However, TARE is also associated with radiation-induced lung injury due to hepatopulmonary shunting. If a large proportion of the injected radionuclide microspheres (more than 15%) is shunted, a rare but lethal complication may develop: radiation-induced pneumonitis (RP). Diffusion capacity of the lungs for carbon monoxide (DLCO) is a valuable test to assess lung function and a decrease in DLCO may indicate an impairment in gas exchange caused by the lung injury. Some previous researches have been reported the most consistent changes in pulmonary function tests after external beam radiotherapy are recorded with DLCO. This study aimed to examine the changes in DLCO after TARE with glass microspheres in newly treated and retreated patients with relatively higher lung shunt fractions.

METHODS: We prospectively analyzed forty consecutive patients with liver malignancies who underwent lobar or superselective TARE with ⁹⁰Y glass microspheres. DLCO tests were performed at baseline and on days 15, 30, and 60 after the treatment. All patients were followed up clinically and radiologically for the development of RP.

RESULTS: A statistically significant decrease was found in the DLCO after the first treatment (81.4 ± 13.66 vs. 75.25 ± 13.22, p = 0.003). The frequency of the patients with impaired DLCO at baseline was significantly increased after the first treatment (37.5 vs 57.5% p < 0.05). In the retreated group (n = 8), neither the DLCO (71.5 ± 10.82 vs. 67.50 ± 11.24, p = 0.115) nor the frequency of patients with impaired DLCO (25 vs 25%, p = 1) did not significantly change. Also, the change in DLCO values did not significantly correlate with lung shunt fraction, administered radiation dose, and absorbed lung dose after the first and second treatments (p > 0.05 for all). None of the patients developed RP.

CONCLUSION: Our study showed that a significant reduction in DLCO after TARE may occur in patients with relatively higher lung shunt fractions. Further studies with larger sample sizes are needed to better investigate the changes in DLCO in patients with high lung shunt fractions.

PMID:36436111 | DOI:10.1007/s12149-022-01810-z

Eur Arch Otorhinolaryngol. 2022 Nov 27. doi: 10.1007/s00405-022-07756-2. Online ahead of print.

ABSTRACT

PURPOSE: The aims of this study were to compare speech recognition at different postoperative times for both ears in bilaterally implanted patients and to assess the influence of the time of deafness, frequency-to-place mismatch, angular insertion depth (AID) and angular separation between neighbouring electrode contacts on audiometric outcomes.

METHODS: This study was performed at an academic tertiary referral centre. A total of 19 adult patients (6 men, 13 women), who received sequential bilateral implantation with lateral wall electrode arrays, were analysed in retrospective. Statistical analysis was performed using two-sided t test, Wilcoxon test, median test, and Spearman’s correlation.

RESULTS: Postlingually deafened patients (deafness after the age of 10) had a significantly better speech perception (WRS65[CI]) than the perilingually deafened subjects (deafness at the age of 1-10 years) (p < 0.001). Comparison of cochlear duct length between peri- and postlingually deafened subjects showed a slightly significantly smaller cochleae in perilingual patients (p = 0.045). No association between frequency-to-place mismatch as well as angular separation and speech perception could be detected. There was even no significant difference between the both ears in the intraindividual comparison, even if insertion parameters differed.

CONCLUSION: The exact electrode position seems to have less influence on the speech comprehension of CI patients than already established parameters as preoperative speech recognition or duration of deafness.

PMID:36436080 | DOI:10.1007/s00405-022-07756-2

J Neurol. 2022 Nov 27. doi: 10.1007/s00415-022-11486-0. Online ahead of print.

ABSTRACT

BACKGROUND: Frontal cortico-subcortical dysfunction may contribute to fatigue and dual-task impairment of walking and cognition in progressive multiple sclerosis (PMS).

PURPOSE: To explore the associations among fatigue, dual-task performance and structural and functional abnormalities of frontal cortico-subcortical network in PMS.

METHODS: Brain 3 T structural and functional MRI sequences, Modified Fatigue Impact Scale (MFIS), dual-task motor and cognitive performances were obtained from 57 PMS patients and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connections and their resting state effective connectivity (RS-EC) with fatigue and dual-task performance were investigated using random forest.

RESULTS: Thirty-seven PMS patients were fatigued (F) (MFIS ≥ 38). Compared to HC, non-fatigued (nF) and F-PMS patients had significantly worse dual-task performance (p ≤ 0.002). Predictors of fatigue (out-of-bag [OOB]-accuracy = 0.754) and its severity (OOB-R² = 0.247) were higher Expanded Disability Status scale (EDSS) score, lower RS-EC from left-caudate nucleus to left-DLPFC, lower fractional anisotropy between left-caudate nucleus and left-thalamus, higher mean diffusivity between right-caudate nucleus and right-thalamus, and longer disease duration. Microstructural abnormalities in connections among thalami, caudate nuclei and DLPFC, mainly left-lateralized in nF-PMS and more bilateral in F-PMS, higher RS-EC from left-DLPFC to right-DLPFC in nF-PMS and lower RS-EC from left-caudate nucleus to left-DLPFC in F-PMS, higher EDSS score, higher WM lesion volume, and lower cortical volume predicted worse dual-task performances (OOB-R² from 0.426 to 0.530).

CONCLUSIONS: In PMS, structural and functional frontal cortico-subcortical abnormalities contribute to fatigue and worse dual-task performance, with different patterns according to the presence of fatigue.

PMID:36436069 | DOI:10.1007/s00415-022-11486-0

Arch Orthop Trauma Surg. 2022 Nov 27. doi: 10.1007/s00402-022-04696-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Arthrofibrosis remains a common cause of patient dissatisfaction and reoperation after total knee arthroplasty (TKA). Losartan is an angiotensin receptor blocker (ARB) with inhibitory effects on transforming growth factor beta, previously implicated in tissue repair induced fibrosis, and has been studied to prevent stiffness following hip arthroscopy. This study aimed to evaluate pre- and postoperative range of motion (ROM) and the incidence of manipulation under anesthesia (MUA) following primary TKA in patients taking Losartan preoperatively for hypertension.

MATERIALS AND METHODS: A retrospective review of 170 patients from 2012 to 2020 who underwent a primary, elective TKA and were prescribed Losartan at least three months prior to surgery. All patients who were prescribed Losartan and had a preoperative and postoperative ROM in their chart were included and were matched to a control group of patients who underwent TKA and had no Losartan prescription. ROM, MUA, readmissions, reoperations, and revisions were assessed using chi-square and independent sample t tests.

RESULTS: Seventy-nine patients met the inclusion criteria. Preoperative ROM was similar between patients on Losartan and the control group (103.59° ± 16.14° vs. 104.59° ± 21.59°, respectively; p = 0.745). Postoperative ROM and ΔROM were greater for patients prescribed Losartan (114.29° ± 12.32° vs. 112.76° ± 11.65°; p = 0.429 and 10.57° ± 14.95° vs. 8.17° ± 21.68°; p = 0.422), though this difference did not reach statistical significance. There was no difference in readmission, rate of manipulation for stiffness, or all-cause revision rates.

CONCLUSION: In this study, we found that the use of Losartan did not significantly improve postoperative ROM, reduce MUA or decrease revision rates. Further prospective studies using Losartan are required to elucidate the potential effects on ROM and incidence of arthrofibrosis requiring MUA.

LEVEL III EVIDENCE: Retrospective cohort study.

PMID:36436067 | DOI:10.1007/s00402-022-04696-8