OBJECTIVE: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care.
METHODS: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new \"CIDP treatment-response category\" (CT-RC), based on achieved endpoints. Determinants of the CT-RC, of timing of maximum improvement, and of treatment discontinuation were ascertained.
RESULTS: The CT-RC demonstrated high concurrent validity with current outcome measures. Thirty-six subjects (32.1%) achieved a \"complete response,\" 37 (33%) a \"good partial response,\" 10 (8.9%) a \"moderate partial response,\" and 15 (13.4%) a \"poor partial response.\" Fourteen subjects (12.5%) were \"nonresponsive.\" The CT-RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1-36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders.
CONCLUSIONS: CT-RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician- and patient-related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP.

BACKGROUND: Approximately 20 % of femoral fragility fracture patients take anticoagulants, typically warfarin or Direct Oral AntiCoagulant (DOAC). These can impact timing of surgery affecting patient survival. Due to several possible approaches and numerous factors to consider in the preoperative workup of anticoagulated patients, potential for variations in clinical practice exist. Some hospitals employ dedicated anticoagulation management protocols to address this issue, and to improve time to surgery. This study aimed to determine the proportion of hospitals with such protocols, compare protocol guidance between hospitals, and evaluate the effectiveness of protocols in facilitating prompt surgery.
METHODS: Data was prospectively collected through a collaborative, multicentre approach involving hospitals across the UK. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Information from dedicated anticoagulation management protocols were collated on several domains relating to perioperative care including administration of reversal agents and instructions on timing of surgery as well as others. Logistic regression was used to evaluate effects of dedicated protocols on time to surgery.
RESULTS: Dedicated protocols for management of patients taking warfarin and DOACs were present at 41 (52.6 %) and 43 (55.1 %) hospitals respectively. For patients taking warfarin, 39/41 (95.1 %) protocols specified the dose of vitamin k and the most common was 5 milligrams intravenously (n=21). INR threshold values for proceeding to surgery varied between protocols; 1.5 (n=28), 1.8 (n=6), and 2 (n=6). For patients taking DOACs, 35/43 (81.4 %) and 8/43 (18.6 %) protocols advised timing of surgery based on renal function and absolute time from last dose respectively. Analysis of 10,197 patients from 78 hospitals showed fewer patients taking DOACs received surgery within 36 h of admission at hospitals with a dedicated protocol compared to those without (adjusted OR 0.73, 95% CI 0.54-0.99, p=0.040), while there were no differences among patients taking warfarin (adjusted OR 1.64, 95% CI 0.75-3.57, p=0.219).
CONCLUSIONS: Around half of hospitals employed a dedicated anticoagulation management protocol for femoral fragility fracture patients, and substantial variation was observed in guidance between protocols. Dedicated protocols currently being used at hospitals were ineffective at improving the defined targets for time to surgery.

BACKGROUND: Vasopressor administration at an appropriate time is crucial but the optimal timing remains controversial.
OBJECTIVE: Does early versus late norepinephrine (NE) administration impact the prognosis of septic shock?
METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into early and late NE group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the intensive care unit, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume.
RESULTS: Twelve studies (4 randomized controlled trials [RCTs], 8 observational) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early NE group and late NE group in RCTs (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower intravenous fluid volumes, the early NE group showed significantly lower mortality than the late NE group (OR 0.49, 95%, CI, 0.25-0.96). The early NE group demonstrated more mechanical ventilator-free days in observational studies (MD, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early NE group in the three RCTs that reported this outcome (OR 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes.
CONCLUSIONS: Overall mortality did not differ significantly between early and late NE administration for septic shock. However, early NE administration appeared to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early NE use.

UNASSIGNED: Although there have been several studies describing risk factors for complications after outpatient total hip arthroplasty (THA), data describing the timing of such complications is lacking.
UNASSIGNED: Patients who underwent outpatient or inpatient primary THA were identified in the 2012-2019 National Surgical Quality Improvement Program database. For 9 different 30-day complications, the median postoperative day of diagnosis was determined. Multivariable regressions were used to compare the risk of each complication between outpatient vs inpatient groups. Multivariable Cox proportional hazards modeling was used to evaluate the differences in the timing of each adverse event between the groups.
UNASSIGNED: After outpatient THA, the median day of diagnosis for readmission was 12.5 (interquartile range 5-22), surgical site infection 15 (2-21), urinary tract infection 13.5 (6-19.5), deep vein thrombosis 13 (8-21), myocardial infarction 4.5 (1-7), pulmonary embolism 15 (8-25), sepsis 16 (9-26), stroke 2 (0-7), and pneumonia 6.5 (3-10). On multivariable regressions, outpatients had a lower relative risk (RR) of readmission (RR = 0.73), surgical site infection (RR = 0.72), and pneumonia (RR = 0.1), all P < .05. On multivariable cox proportional hazards modeling, there were no statistically significant differences in the timing of each complication between outpatient vs inpatient procedures (P > .05).
UNASSIGNED: The timing of complications after outpatient THA was similar to inpatient procedures. Consideration should be given to lowering thresholds for diagnostic testing after outpatient THA for each complication during the at-risk time periods identified here. Although extremely rare, this is especially important for catastrophic adverse events, which tend to occur early after discharge.

Current scientific literature is deficient in detailing the optimal timing for conducting bariatric surgery in relation to kidney transplantation. In this study, we performed a retrospective evaluation of kidney transplant recipients with BMI >35 kg/m2. It aimed to provide data on those who received both sleeve gastrectomy (SG) and kidney transplantation (KT) simultaneously, as well as on patients who underwent SG and KT at different times, either before or after. In addition, the acceptance levels of the bariatric surgery among different scenarios were assessed. Our findings demonstrated that combined KT and SG led to successful weight loss, in contrast to undergoing kidney transplant alone, while maintaining comparable rates of graft and patient survival. Weight loss was similar between recipients who had a combined operation and those who underwent SG following the transplant. Additionally, over a median time frame of 1.7 years, patients who underwent SG before KT exhibited a statistically significant reduction in BMI at the time of the transplant. Notably, our study highlights that patients offered the combined procedure were significantly more likely to undergo SG compared to those for whom SG was presented at a different operative time than the transplant.

OBJECTIVE: Previous studies examining bidirectional relationships between nocturnal sleep and napping have focused on sleep duration, leaving a gap in our understanding of how sleep timing contributes. Here, we assessed duration and timing for night sleep and daytime naps, to evaluate how the previous night\'s sleep influences next day napping, and how napping influences same-night nocturnal sleep.
METHODS: We analysed sleep diary and actigraphy data from 153 teens (males = 43.8%, mean age = 16.6 years). Participants who never napped were excluded. Nocturnal sleep-nap relationships were investigated using logistic and linear regression models separately for weekdays and weekends.
RESULTS: Participants napped an average of 2.3 times a week. 167 school day naps and 107 weekend were recorded. Naps were on average 82.12 ± 53.34 mins and average nap onset was 14:58 ± 3.78 h. Their duration, start and end times did not significantly differ between weekdays and weekends. Nocturnal sleep duration did not predict next day nap occurrence or duration. However, on school days, earlier wake times significantly increased the likelihood of napping that day, and advanced nap timing. On weekends, later bedtimes and wake times delayed nap timing. On school days, napping longer than one\'s average shortened nocturnal sleep whereas on weekends, waking from a nap later than one\'s average delayed bedtimes.
CONCLUSIONS: Early wake times increase the likelihood of napping and advance the time of a nap that day. Naps may be detrimental to the same-night\'s sleep only if they are long and occur late, as these can delay bedtimes and shorten nocturnal sleep duration, especially on school days.

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Converging experimental and computational evidence indicate that on the scale of seconds the brain encodes time through changing patterns of neural activity. Experimentally, two general forms of neural dynamic regimes that can encode time have been observed: neural population clocks and ramping activity. Neural population clocks provide a high-dimensional code to generate complex spatiotemporal output patterns, in which each neuron exhibits a nonlinear temporal profile. A prototypical example of neural population clocks are neural sequences, which have been observed across species, brain areas, and behavioral paradigms. Additionally, neural sequences emerge in artificial neural networks trained to solve time-dependent tasks. Here, we examine the role of neural sequences in the encoding of time, and how they may emerge in a biologically plausible manner. We conclude that neural sequences may represent a canonical computational regime to perform temporal computations.

Our ability to perceive event duration and order is critical in every aspect of our lives, from everyday tasks like coordinating our limbs to walk safely, to uniquely human activities like planning our children\'s future. Many theoretical accounts of timing have been proposed to explain the mechanisms underlying our ability to estimate time and unify events in time. Continuous progress is being met in further refining and extending current theories, with the aim not only to advance our understanding of timing and time perception, but also to make timing more accessible and applicable to daily life. For this to be possible, cross-disciplinary thinking is required, which is something one cannot easily attain in a scientific conference, rather it requires a community. Having a community with an interest and/or expertise in timing can allow for cross-fertilization of ideas. This chapter introduced the story of the Timing Research Forum or else TRF.

BACKGROUND: The effects of the timing of surgical repair on the outcomes of traumatic and non-traumatic rotator cuff injuries (RCI) remain elusive. Thus, this study aimed to compare differences in outcomes following the repair of traumatic and non-traumatic RCI at varying time points.
METHODS: The study population comprised 87 patients with traumatic and non-traumatic RCI who underwent arthroscopic rotator cuff repair and were followed up for a minimum of 6 months. Next, the trauma and the non-trauma groups were stratified into subgroups according to the time of injury (early repair: occurring within 3 months; delayed repair: occurring after 3 months). Measurements before and after surgical interventions were compared to evaluate the effect of the duration of RCI on the functional status of patients in the trauma and non-trauma groups. Primary evaluation indices included the Visual Analog Scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder function score, and the University of California, Los Angeles (UCLA) shoulder score. Secondary evaluation indices consisted of shoulder range of motion (ROM), postoperative rotator cuff retear rate, and incidence of joint stiffness.
RESULTS: Among the 40 patients in the trauma group, 22 underwent early repair, whereas the remaining 18 underwent delayed repair. In the non-trauma group consisting of 47 patients, 18 underwent early repair, whereas the remaining 29 underwent delayed repair. The minimum clinical follow-up time was 6 months, with an average follow-up time of 10.2 months. During postoperative follow-up, 1 and 6 patients who underwent early and delayed repair experienced re-tear in the trauma group, respectively. Contrastingly, 3 and 8 patients who underwent early and delayed repair presented with re-tear in the non-trauma group, respectively.
CONCLUSIONS: Early repair of traumatic RCI yielded superior outcomes, including improved range of motion, lower pain symptoms, and lower risk of postoperative re-tears compared to delayed repair. Additionally, non-surgical treatment is recommended as the preferred approach for patients with non-traumatic RCI.