J Clin Psychiatry. 2022 Nov 30;83(6):22f14722. doi: 10.4088/JCP.22f14722.

ABSTRACT

Three drug dosing strategies can be employed to address dose-dependent drug adverse effects. The usual strategy is to continue the drug but at a lower dose; it would then take 5 half-lives of the drug for the new steady state to be attained and for a dose-dependent adverse effect to correspondingly attenuate. Such slow offset of the adverse effect could be disadvantageous for drugs such as fluoxetine, penfluridol, and cariprazine that have long half-lives. A second strategy is to stop the drug and to resume it at a lower dose when the adverse effect attenuates as the drug blood level falls. This strategy introduces subjectivity in timing the reintroduction of the drug, requires closer patient monitoring, and risks nonadherence and relapse. The third strategy is to stop the drug for a prespecified number of days and to then reintroduce it at a lower dose. From a knowledge of pharmacokinetics, it can be shown that stopping a drug for just 1 half-life and then resuming it at half the dose results in the immediate achievement of steady state; that is, there is no need to wait for 4 additional half-lives as with the usual strategy of dose reduction without dosing interruption. A limitation of this pharmacokinetically driven dosing strategy, however, is that it would work well in the average patient but not in those with outlying pharmacokinetic parameters.

PMID:36449476 | DOI:10.4088/JCP.22f14722

JAMA Netw Open. 2022 Nov 1;5(11):e2244412. doi: 10.1001/jamanetworkopen.2022.44412.

ABSTRACT

IMPORTANCE: Attrition in cancer clinical trials (CCTs) can lead to systematic bias, underpowered analyses, and a loss of scientific knowledge to improve treatments. Little attention has focused on retention, especially the role of perceived benefits and burdens, after participants have experienced the trial.

OBJECTIVES: To examine the association between patients' perceived benefits and burdens of research participation and CCT retention.

DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted at a National Cancer Institute-designated comprehensive cancer center in the Northeast region of the US. The sample included adult patients with a cancer diagnosis participating in cancer therapeutic trials. Data were collected from September 2015 to June 2019. Analysis of study data was ongoing since November 2019 through October 2022.

EXPOSURES: Self-reported validated survey instrument with a list of 22 benefits and 23 burdens of research participation that can be rated by patients with a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree).

MAIN OUTCOMES AND MEASURES: A primary outcome was actual withdrawal from the CCT, and a composite outcome was composite withdrawal that included both actual withdrawal and thoughts of withdrawing. Bivariate and multivariable logistic regressions were used.

RESULTS: Among the 334 participants in the sample, the mean (SD) age was 61.9 (11.5) years and 174 women (52.1%) were included. Top-cited benefits included both aspirational and action-oriented goals, including helping others (94.2%), contributing to society (90.3%), being treated respectfully (86.2%), and hoping for a cure (86.0%). Worry over receiving a placebo (61.3%), rearranging one's life (41.9%), and experiencing bothersome adverse effects (41.6%) were notable burdens. An increased burden score was associated with a higher probability of actual withdrawal (adjusted odds ratio [OR], 1.86; 95% CI, 1.1-3.17; P = .02) or composite withdrawal (adjusted OR, 3.44; 95% CI, 2.09-5.67; P < .001). An increased benefit score was associated with lower composite withdrawal (adjusted OR, 0.40; 95% CI, 0.24-0.66; P < .001). For participants who reported the benefits as being equal to or greater than the burdens, 13.4% withdrew. For those who perceived the benefits as being less than the burdens, 33.3% withdrew (adjusted OR, 3.38; 95% CI, 1.13-10.14; P = .03). The risk of withdrawal was even higher for the composite outcome (adjusted OR, 7.70; 95% CI, 2.76-21.48; P < .001).

CONCLUSIONS AND RELEVANCE: This survey study found that patients perceived important benefits from CCT participation, and this perception was associated with trial retention, even among those who also perceived substantial burdens. A broader dialogue among stakeholders can inform an ethical and patient-centric focus on benefits throughout the course of a CCT to increase retention.

PMID:36449287 | DOI:10.1001/jamanetworkopen.2022.44412

Cancer Treat Res. 2022;184:141-149. doi: 10.1007/978-3-031-04402-1_10.

ABSTRACT

Adverse drug/device reactions (ADRs) serious enough to lead to box warnings on drug labels or drug withdrawals occur in about one fifth of all new molecular entities.

PMID:36449194 | DOI:10.1007/978-3-031-04402-1_10

Cancer Treat Res. 2022;184:129-140. doi: 10.1007/978-3-031-04402-1_9.

ABSTRACT

Severe adverse drug reactions (sADRs) are important causes of morbidity and mortality. The Southern Network on Adverse Drug Reactions (SONAR), a National Cancer Institute-funded pharmacovigilance program, has outlined a novel 9-stop methodology, termed ANTICIPATE, that has evaluated this methodology, among persons with chronic kidney disease (CKD).

PMID:36449193 | DOI:10.1007/978-3-031-04402-1_9

Cancer Treat Res. 2022;184:87-102. doi: 10.1007/978-3-031-04402-1_6.

ABSTRACT

More than half of all serious adverse drug reactions are identified seven years after FDA approval. One recent and unusual example involves a syndrome initially termed nephrogenic dermatopathic fibrosis, and then called nephrogenic systemic fibrosis (NSF).

PMID:36449190 | DOI:10.1007/978-3-031-04402-1_6

Cancer Treat Res. 2022;184:75-85. doi: 10.1007/978-3-031-04402-1_5.

ABSTRACT

About 1-10% of all serious adverse drug reactions (sADRs) are reported to the Food and Drug Administration (FDA) ( Moore T, Bennett C. Underreporting of Hemorrhagic and Thrombotic Complications of Pharmaceuticals to the U.S. Food and Drug Administration: Empirical Findings for Warfarin, Clopidogrel, Ticlopidine, and Thalidomide from the Southern Network on Adverse Reactions (SONAR). Semin Thromb Hemost. 2012;38(08):905-907. https://doi.org/10.1055/s-0032-1328890 ). Prevailing opinion suggests that low reporting rates reflect time constraints.

PMID:36449189 | DOI:10.1007/978-3-031-04402-1_5

J Int Med Res. 2022 Nov;50(11):3000605221138480. doi: 10.1177/03000605221138480.

ABSTRACT

The combination of sacubitril and valsartan has recently become eligible for reimbursement in Japan for the treatment of hypertension. However, the real-world clinical efficacy of sacubitril/valsartan in patients with hypertension who are taking multiple anti-hypertensive medications remains to be characterized. We treated a man in his late 40s who had undergone a percutaneous coronary intervention and had hypertension that was refractory to multiple anti-hypertensive medications. We initiated sacubitril/valsartan 200 mg/day as an add-on therapy, and 3 months later, his blood pressure had decreased from 154/78 mmHg to 134/70 mmHg, in the absence of any drug-related adverse events. Furthermore, his left ventricular mass index had improved from 135 g/m2 to 112 g/m2. Thus, sacubitril/valsartan might ameliorate hypertrophy in patients with hypertension.

PMID:36448517 | DOI:10.1177/03000605221138480

BMC Health Serv Res. 2022 Nov 28;22(1):1438. doi: 10.1186/s12913-022-08862-x.

NO ABSTRACT

PMID:36443812 | PMC:PMC9706996 | DOI:10.1186/s12913-022-08862-x

J Int Med Res. 2022 Nov;50(11):3000605221138455. doi: 10.1177/03000605221138455.

ABSTRACT

OBJECTIVE: Some drugs have adverse effects on glucose metabolism, but it is unknown whether prescription drugs used prior to conception influence the future risk of gestational diabetes mellitus (GDM). Our study evaluated whether the purchase of prescription drugs 6 months prior to conception was associated with the occurrence of GDM.

METHODS: This cohort study enrolled women with a Finnish background who delivered between 2009 and 2015 in the city of Vantaa, Finland (N = 10,455). Data on maternal characteristics and prescription drug purchases were obtained from national health registers. The use of a unique personal identification number enabled us to combine the register data on an individual level.

RESULTS: Six months prior to conception, women who had pregnancies complicated by GDM purchased more prescription drugs than women without GDM (1.38 ± 2.04 vs. 1.11 ± 1.80). The GDM risk was higher in women with higher numbers of prescription purchases and those with more than three deliveries.

CONCLUSIONS: Multiparous women who purchase several prescription drugs should be given personalized counseling to prevent GDM.

PMID:36446764 | DOI:10.1177/03000605221138455

Neurol Neuroimmunol Neuroinflamm. 2022 Nov 29;10(1):e200058. doi: 10.1212/NXI.0000000000200058. Print 2023 Jan.

ABSTRACT

BACKGROUND AND OBJECTIVES: To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.

METHODS: Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015-2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018-2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.

RESULTS: Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44-76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5-18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, p = 0.02) and limbic (54% vs 14%, p < 0.01), brainstem (27% vs 5%, p = 0.02), and dorsal root ganglia (45% vs 5%, p < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, p = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, p < 0.01) and higher mortality (91% vs 46%, p < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, p < 0.01) and higher mortality (26%, p < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.

DISCUSSION: The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.

PMID:36446613 | PMC:PMC9709718 | DOI:10.1212/NXI.0000000000200058

BMJ Open. 2022 Nov 29;12(11):e065520. doi: 10.1136/bmjopen-2022-065520.

ABSTRACT

INTRODUCTION: Neurodevelopmental disorders are a group of disorders thought to be associated with the functioning of the brain and the nervous system. Children with neurodevelopmental disorders often have sleep-related comorbidities that may negatively affect quality of life for both the children and their families. Melatonin is one of the most used interventions in children with neurodevelopmental disorders and sleep disorders. Previous reviews have investigated the effects of melatonin for sleep disorders in children with neurodevelopmental disorders, but these had important limitations, such as inadequate analysis of adverse effects, small sample sizes and short follow-up.

METHODS AND ANALYSIS: This is a protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. The protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will search for published and unpublished trials in the Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, PsycINFO, ClinicalTrials.gov and the International Clinical Trials Registry Platform. We will search the databases from their inception without language restrictions. We will also request clinical study reports from regulatory authorities and pharmaceutical companies. Review authors working in pairs will screen reports, extract data and conduct risk of bias assessments using the Cochrane Risk of Bias tool. We will include randomised clinical trials comparing melatonin versus placebo or no intervention for sleep disorders in children with neurodevelopmental disorders. Primary outcomes will be total sleep time and adverse effects. Secondary outcomes will be quality of life of the child and caregivers and sleep onset latency. Data will be analysed using random-effects and fixed-effect meta-analyses. Certainty of evidence will be assessed with Grading of Recommendations, Assessment, Development and Evaluation approach.

ETHICS AND DISSEMINATION: Ethical approval was not required for this protocol. The systematic review will be published in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42022337530.

PMID:36446459 | PMC:PMC9710329 | DOI:10.1136/bmjopen-2022-065520

Cutis. 2022 Sep;110(3):E19-E20. doi: 10.12788/cutis.0632.

NO ABSTRACT

PMID:36446123 | DOI:10.12788/cutis.0632

Cutis. 2022 Oct;110(4):201-206. doi: 10.12788/cutis.0627.

ABSTRACT

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.

PMID:36446101 | DOI:10.12788/cutis.0627

Oncology (Williston Park). 2022 Nov 8;36(11):658-663. doi: 10.46883/2022.25920978.

ABSTRACT

Small studies have demonstrated the benefit of integrative oncology (IO) therapies in patients with breast cancer; however, referral patterns and timing of therapies are unknown. This study describes the referral pattern and utilization of IO services by young women with breast cancer. A retrospective review identified female patients, 40 years or younger, with a breast cancer diagnosis between 2014 and 2019, and a documented IO consultation. Patient demographics, cancer characteristics, treatments, reasons for seeking and timing of IO consultation, and IO treatment modalities were analyzed. The IO program treated 64 young women with a median age of 38.6 years. Clinical staging was primarily IA (27%), IIA (34%), or IIB (27%), and 64% of patients were clinically node negative with no evidence of metastasis. Women utilized the IO program for recurrence risk reduction and for treatment-related adverse effects (TRAEs), most commonly vasomotor complaints (44%). Therapies utilized were acupuncture (36%), healing touch (28%), oncology massage (30%), and other (75%; music therapy, therapeutic art, spiritual care, meditation, t'ai chi, yoga, and nutrition), which were commonly initiated during treatment (69%). Our data suggest that young women utilize IO services to reduce their future cancer risk and TRAEs, but they are often referred after standard cancer care treatments have begun. Future studies could examine the optimal timing for IO intervention.

PMID:36445978 | DOI:10.46883/2022.25920978

Cochrane Database Syst Rev. 2022 Nov 29;11(11):CD012053. doi: 10.1002/14651858.CD012053.pub2.

ABSTRACT

BACKGROUND: Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction or cessation of treatment, which have an impact on survival. Coriolus versicolor (Trametes versicolor or 'Turkey Tail') mushroom and its extracts have been used by cancer patients to help with adverse effects.

OBJECTIVES: To assess the effects of adjunctive Coriolus versicolor (Trametes versicolor) and its extracts on adverse effects and on survival during colorectal cancer treatment (chemotherapy and radiotherapy) compared with no adjunctive treatment.

SEARCH METHODS: We searched databases including CENTRAL, MEDLINE, Embase, AMED and CINAHL, Chinese and Japanese databases, and trials registers to 12th April 2022 without restriction of language or publication status. We screened reference lists and attempted to contact researchers in the field to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating the efficacy and safety of Coriolus versicolor and its extracts in adult participants with a confirmed diagnosis of colorectal cancer, in addition to conventional treatment. Interventions included any preparation of Coriolus versicolor (raw, decoction, capsule, tablet, tincture, extract, injection), any part of the fungus (cap, stem, mycelium or whole), in any dose or regimen. Outcomes included adverse events rates, survival, disease progression and recurrence, response rates and quality of life.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We evaluated the overall certainty of evidence using the GRADE approach.

MAIN RESULTS: We included seven parallel RCTs (1569 participants). Six studies (1516 participants) were conducted in Japan and one study (53 participants) in China. Studies included both male and female participants with colorectal cancer (five studies), colon cancer (one study) or rectal cancer (one study). Participants were diagnosed with cancer ranging from stage II to stage IV. Coriolus was used in the form of an extract in all seven studies and was generally used after curative resection, although in one study it was used preoperatively. Duration of treatment with the extract varied between four weeks and three years. Chemotherapeutic regimens in six studies consisted of an oral fluoropyrimidine which was preceded by weekly intravenous 5-Fluorouracil (5-FU) in one study, by mitomycin C in two studies, and which was combined with folinic acid (Leucovorin) in two studies and with radiotherapy preoperatively in one study. XELOX (oxaliplatin intravenous infusion and capecitabine) was used in the remaining study. We found very low-certainty evidence of little to no effect of adjunctive treatment with Coriolus (in the form of an extract, polysaccharide-Krestin, PSK) on withdrawal from treatment due to adverse events (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.45 to 2.34; 703 participants; 3 studies;). We are uncertain whether adjunctive Coriolus versicolor and its extracts compared to usual care alone resulted in a difference in adverse events including neutropenia (RR 0.41, 95% CI 0.24 to 0.71; 133 participants; 3 studies; very low certainty), oral cavity disorders such as oral dryness and mucositis (RR 0.37, 95% CI 0.13 to 1.03; 1022 participants; 5 studies; very low certainty), nausea (RR 0.73, 95% CI 0.44 to 1.22; 969 participants; 4 studies; very low certainty), diarrhoea (RR 0.77, 95% CI 0.32 to 1.86; 1022 participants; 5 studies; very low certainty), and fatigue (RR 0.76; 95% CI 0.33 to 1.78; 133 participants; 3 studies; very low certainty). We found low-certainty evidence of a small effect of adjunctive Coriolus on improved survival at five years compared with no adjunctive care (RR 1.08, 95% CI 1.01 to 1.15; 1094 participants; 3 studies; number needed to benefit (NNTB) = 16 (95% Cl 9 to 70). The effect at earlier time points was unclear.

AUTHORS' CONCLUSIONS: Due to the very low certainty of evidence, we were uncertain about the effect of adjunctive Coriolus (in the form of an extract PSK) on adverse events resulting from conventional chemotherapy for colorectal cancer. This includes effects on withdrawal of treatment due to adverse events and on specific adverse outcomes such as neutropenia and nausea. The uncertainty in the evidence also means that it was unclear whether any adverse events were due to the chemotherapy or to the extract itself. While there was low-certainty evidence of a small effect on overall survival at five years, the influence of reduced adverse effects on this could not be determined. In addition, chemotherapy regimens used in assessing this outcome do not reflect current preferred practice.

PMID:36445793 | PMC:PMC9707730 | DOI:10.1002/14651858.CD012053.pub2

JAMA Netw Open. 2022 Nov 1;5(11):e2244141. doi: 10.1001/jamanetworkopen.2022.44141.

ABSTRACT

IMPORTANCE: Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available.

OBJECTIVE: To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients.

DESIGN, SETTING, AND PARTICIPANTS: This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022.

EXPOSURES: Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy.

MAIN OUTCOMES AND MEASURES: Clinical characteristics and outcomes were ascertained through manual record review.

RESULTS: Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities.

CONCLUSIONS AND RELEVANCE: In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

PMID:36445705 | DOI:10.1001/jamanetworkopen.2022.44141

J Cutan Pathol. 2022 Dec;49(12):1051-1059. doi: 10.1111/cup.14306. Epub 2022 Aug 18.

ABSTRACT

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern.

METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified.

RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04).

CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

PMID:36445270 | PMC:PMC9709294 | DOI:10.1111/cup.14306

Alzheimers Res Ther. 2022 Nov 29;14(1):178. doi: 10.1186/s13195-022-01110-8.

ABSTRACT

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal antibody as the first potential disease-modifying therapy for AD, signaled the value of more than 20 years of drug development, adding to the available therapies the first nominal success since cholinesterase inhibitors and memantine were approved. BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. Key learnings from the field were incorporated into the gantenerumab phase 3 program, including confirmed amyloid positivity as an entry criterion, an enriched clinical trial population to ensure measurable clinical decline, data-driven exposure-response models to inform a safe and efficacious dosing regimen, and the use of several blood-based biomarkers. Subcutaneous formulation for more pragmatic implementation was prioritized as a key feature from the beginning of the gantenerumab development program.

CONCLUSION: The results from the gantenerumab phase 3 programs are expected by the end of 2022 and will add critical information to the collective knowledge on the search for effective AD treatments.

PMID:36447240 | DOI:10.1186/s13195-022-01110-8

Drug Ther Bull. 2022 Nov 29:dtb-2022-000067. doi: 10.1136/dtb.2022.000067. Online ahead of print.

ABSTRACT

Overview of: Carbone F, Van den Houte K, Besard L, et al Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Gut 2022;71:2226-32.

PMID:36446551 | DOI:10.1136/dtb.2022.000067

BMJ Open. 2022 Nov 28;12(11):e063921. doi: 10.1136/bmjopen-2022-063921.

ABSTRACT

INTRODUCTION: Here, we provide a feasible, well-designed protocol of a randomised controlled trial for the assessment of the effects of a home-based multidisciplinary intervention on the severity of skin adverse drug reactions and health-related indicators in patients with non-small cell lung cancer (NSCLC) under epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy.

METHODS AND ANALYSIS: The study will be a two-group, parallel randomised controlled trial conducted at patients' homes by a multidisciplinary team in Zhengzhou in Henan Province, China. Patients with NSCLC who received EGFR-TKI therapy and experienced adverse skin reactions will be randomised and receive either ordinary care or home-based multidisciplinary interventions. The intervention will be divided into an intensive stage (6 weeks) and a maintenance stage (6 weeks) with baseline and follow-up assessment. Interventions in the intensive stage will include general interventions such as health education, follow-up, behaviour guide and social support and targeted interventions such as skill training, coping with adverse drug reaction and problem-solving. The measures that will be carried out in maintenance stage are continuous interventions consisted of an intensive intervention. The multidisciplinary team will be responsible for managing skin adverse drug reactions as required at patients' homes. Data collection and analysis will be performed by researchers at baseline, the end of the sixth week of intervention and the third month after the intervention. The primary outcome is the degree of skin adverse drug reactions, while the secondary outcomes, for example, self-management ability, quality of life, outpatient visits and health economics indicators, will also be presented.

ETHICS AND DISSEMINATION: This study was reviewed and approved by the Ethics Committee of Zhengzhou University (No. ZZUIRB-2020-97). Findings will be available to patients, clinicians, nurses, pharmacists, community medical staff, funders and health policymakers through peer-reviewed publications, social media and patient support groups.

TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2000040643).

PMID:36442902 | DOI:10.1136/bmjopen-2022-063921