Abstract：
BACKGROUND: The ideal timing for initiating levodopa in newly diagnosed people with Parkinson\'s disease (PD) is uncertain due to limited data on the long-term effects of levodopa.
OBJECTIVE: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries.
METHODS: Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as \"early initiators\" (initiating levodopa within 2 years of diagnosis) or \"nonearly initiators.\" We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates.
RESULTS: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05).
CONCLUSIONS: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.
OBJECTIVE: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries.
METHODS: Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as \"early initiators\" (initiating levodopa within 2 years of diagnosis) or \"nonearly initiators.\" We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates.
RESULTS: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05).
CONCLUSIONS: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.
摘要：
背景：由于关于左旋多巴长期影响的数据有限，在新诊断的帕金森病（PD）患者中启动左旋多巴的理想时机尚不确定。
目的：目的是调查左旋多巴早期启动是否会延缓死亡率（主要结局），设备辅助治疗的要求，和PD相关并发症的发生率，例如跌倒引起的伤害。
方法：使用荷兰医院的全国索赔数据（2012-2020年），我们将新诊断的PD个体分为"早期启动者"(在诊断后2年内启动左旋多巴)或"非早期启动者.“我们使用国家死亡登记来评估死亡率和医疗保健声明，以评估与PD相关的并发症和设备辅助治疗。我们使用边际结构模型来比较各组之间的死亡率和器械辅助治疗率，和Poisson回归模型比较PD相关并发症发生率。
结果：在29,943名新诊断的PD患者中（诊断平均年龄：71.6，38.5％为女性），有24,847个早期和5096个非早期左旋多巴引发剂。超过4.25年的中位数，8109人（27.1%）死亡。早期与非早期引发者死亡的因果风险比为1.04(95%置信区间[CI]0.92-1.19)。接受任何设备辅助治疗的风险比为3.19（95％CI2.56-5.80）。与PD相关并发症的发生率无相关性（发生率比：1.00，95％CI0.96-1.05）。
结论：PD患者早期启动左旋多巴既不延缓也不加速死亡率或PD相关并发症，它也不会导致PD相关并发症或死亡的早期发生。然而,我们不能排除,由于无法测量的死亡危险因素,结果受到残留混杂因素的影响.
目的：目的是调查左旋多巴早期启动是否会延缓死亡率（主要结局），设备辅助治疗的要求，和PD相关并发症的发生率，例如跌倒引起的伤害。
方法：使用荷兰医院的全国索赔数据（2012-2020年），我们将新诊断的PD个体分为"早期启动者"(在诊断后2年内启动左旋多巴)或"非早期启动者.“我们使用国家死亡登记来评估死亡率和医疗保健声明，以评估与PD相关的并发症和设备辅助治疗。我们使用边际结构模型来比较各组之间的死亡率和器械辅助治疗率，和Poisson回归模型比较PD相关并发症发生率。
结果：在29,943名新诊断的PD患者中（诊断平均年龄：71.6，38.5％为女性），有24,847个早期和5096个非早期左旋多巴引发剂。超过4.25年的中位数，8109人（27.1%）死亡。早期与非早期引发者死亡的因果风险比为1.04(95%置信区间[CI]0.92-1.19)。接受任何设备辅助治疗的风险比为3.19（95％CI2.56-5.80）。与PD相关并发症的发生率无相关性（发生率比：1.00，95％CI0.96-1.05）。
结论：PD患者早期启动左旋多巴既不延缓也不加速死亡率或PD相关并发症，它也不会导致PD相关并发症或死亡的早期发生。然而,我们不能排除,由于无法测量的死亡危险因素,结果受到残留混杂因素的影响.
